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Panitumumab

Phase 3

Colorectal Cancer | Monoclonal antibody | Oncology |Amgen Inc.|Last Updated: Feb 5, 2025

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Trial Design
RandomizedCONTROLLEDDMCBiomarker
Total Trials8
Total Enrollment2,021
FDA Designations
No designations recorded
Clinical trial landscape

Panitumumab · 39 trials · 42 indications

Phase 3 6Phase 2 28Phase 1 5
NCT01412957Comparison of Survival Benefit of Panitumumab With Supportive Care to Best Supportive Care Alone in Patients With Metastatic Colorectal CancerMetastatic Colorectal Cancer
COMPLETED377 Analytics
NCT01001377ASPECCT: A Study of Panitumumab Efficacy and Safety Compared to Cetuximab in Patients With KRAS Wild-Type Metastatic Colorectal CancerMetastatic Colorectal Cancer
COMPLETED1,010 Analytics
NCT00364013PRIME: Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine EfficacyMetastatic Colorectal Cancer
COMPLETED1,183 Analytics
NCT00339183Comparison of Treatment Effect of Chemotherapy With Panitumumab to Chemotherapy AloneMetastatic Colorectal Cancer
COMPLETED1,186 Analytics
NCT00115765PACCE: Panitumumab Advanced Colorectal Cancer Evaluation StudyColorectal Cancer
COMPLETED1,053 Analytics
NCT00113763Evaluating Panitumumab (ABX-EGF) Plus Best Supportive Care Versus Best Supportive Care in Patients With Metastatic Colorectal CancerColorectal Cancer
COMPLETED463 Analytics
PHASE3COMPLETED
Comparison of Survival Benefit of Panitumumab With Supportive Care to Best Supportive Care Alone in Patients With Metastatic Colorectal Cancer
Metastatic Colorectal CancerUnlock trial analytics
PHASE3COMPLETED
ASPECCT: A Study of Panitumumab Efficacy and Safety Compared to Cetuximab in Patients With KRAS Wild-Type Metastatic Colorectal Cancer
Metastatic Colorectal CancerUnlock trial analytics
PHASE3COMPLETED
PRIME: Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy
Metastatic Colorectal CancerUnlock trial analytics
PHASE3COMPLETED
Comparison of Treatment Effect of Chemotherapy With Panitumumab to Chemotherapy Alone
Metastatic Colorectal CancerUnlock trial analytics
PHASE3COMPLETED
PACCE: Panitumumab Advanced Colorectal Cancer Evaluation Study
Colorectal CancerUnlock trial analytics
PHASE3COMPLETED
Evaluating Panitumumab (ABX-EGF) Plus Best Supportive Care Versus Best Supportive Care in Patients With Metastatic Colorectal Cancer
Colorectal CancerUnlock trial analytics
Study Endpoints
Primary Endpoints
Overall Survival
From randomization to the last on-study or long-term follow-up visit, as of the data cut-off date of 10 June 2014. The median follow-up time was 34.9 weeks (panitumumab plus BSC: 41.0 weeks; BSC alone: 25.5 weeks).

Overall survival was defined as the time from the randomization date to the date of death. Participants who had not died by the analysis data cut-off date were censored at their last contact date and participants with survival data obtained after the planned analysis data cut-off date had survival censored at the cut-off date.

Progression-free Survival
From randomization until the data cutoff date of 30 September 2008. Maximum follow-up time was 109 weeks.

Progression-free survival (PFS), assessed by central radiological assessment, was defined as the time from randomization to disease progression per modified response evaluation criteria in solid tumors (RECIST) criteria or death. Participants who were alive but did not meet criteria for progression by the data cutoff date were censored at their last evaluable disease assessment date. Progressive disease is defined as a ≥ 20% increase in the size of target lesions or unequivocal progression of existing non-target lesions or any new lesions.

Progression-free Survival (PFS)
From randomization until the data cut-off date of 8 April 2008. Maximum follow-up time was 17 months.

Progression-free survival was defined as the time from randomization to first disease progression per modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria or death, based on independent central radiological assessment. Participants who were alive but did not meet criteria for progression by the data cutoff date were censored at their last evaluable disease assessment date. Progressive disease is defined as a ≥ 20% increase in the size of target lesions or unequivocal progression of existing non-target lesions or any new lesions.

Progression-Free Survival (Oxaliplatin)
Overall study

Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression

Objective Tumor Response Through Week 12 (Irinotecan)
Overall Study

Objective tumor response (complete or partial) rate through week 12 based on central review in the Irinotecan stratum

Progression-free Survival Time
From randomization to the data cut-off date of 30 June 2005. The median follow-up time was 20.0 weeks in the panitumumab plus BSC group and 18.2 weeks in the BSC alone group.

Kaplan-Meier estimates of median time from randomization to either death or first observed disease progression, whichever occurred first. Participants were evaluated for tumor response according to modified Response Evaluation Criteria in Solid Tumors (RECIST) based on the response assessment from a blinded review of radiographic scans by the Independent Review Committee. Progressive disease defined as least a 20% increase in the sum of the longest diameters (SLD) of target lesions, taking as reference the nadir SLD recorded since the treatment started or the appearance of one or more new lesions, or the unequivocal progression of existing non-target lesions.

Overall Response Rate
up to 60 months

As primary endpoint ORR according to RECIST 1.1 will be evaluated separately for each arm of patients with defined low-frequency RAS mutation

Progression-free survival at one year
12 months after inclusion

Percentage of subjects still alive and progression free 12 months after inclusion in the study

Progression-free survival time according to the MMP7 status (PFS)
5 years

To estimate the PFS by DP immunohistochemistry (IHC) expression in patients with wild-type KRAS mCRC treated with panitumumab and mFOLFOX6. Two groups are established by DP status (MMP7+/p-IGF-IR+ vs. MMP7+/p-IGF-IR-, MMP7-/p-IGF-IR+ or MMP7-/p-IGF-IR-).

Tumor Response Rate Based on Complete Response (CR)+ Partial Response (PR) + Stable Disease (SD)
At baseline and every 8 weeks during treatment until progressive disease for maximum of 51 cycles where 1 cycle = 2 weeks.

Tumor response rate will be measured by CT scan of the chest and CT scan or MRI scan of abdomen and pelvis every 8 weeks until disease progression response rate will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions evaluated using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD)of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions,taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started

Response Rate (RR)
Up to 14 months

Response rate (RR) = the # participants with partial response (PR) + # participants with (CR) / # participants with (PR) + # participants with (CR ) + # participants with (SD) + # participants with (PD). This proportion was subsequently multiplied by 100. RECIST v1.0 criteria for Target Lesions was used: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started

Clinical Benefit Rate (CBR)
Up to 14 months

Using RECIST v1.0 criteria, clinical benefit rate (CBR) = # participants with (PR) + # participants with (CR) + # participants with (SD) / # participants with (PR) + # participants with (CR) + # participants with (SD) + # participants with (PD). This proportion was subsequently multiplied by 100. RECIST v1.0 criteria for Target Lesions is defined as: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Percentage of patients that are treated based on their molecular tumor profile
6 months after treatment initiation (estimated average)

Primary outcome measure 1 is the percentage of submitted patients, that can be treated based on their molecular tumor profile within the context of this protocol.

Objective tumor response
6 months after treatment initiation (estimated average)

Primary outcome measure 2 is the proportion of study participants with an objective tumor response upon study treatment..

Stable disease
6 months after treatment initiation (estimated average)

Primary outcome measure 3 is the proportion of study participants that has stable disease (SD) during study treatment.

Treatment-related grade≥3 and serious adverse events
6 months after treatment initiation (estimated average)

Primary outcome measure 4 is the proportion of patients that experience treatment-related grade≥3 and /or serious adverse events.

Progression Free Survival (PFS)
Time from study day 1 to the time the patient is first recorded as having disease progression or death, assessed up to 3 years

Continuous variables will be expressed by means, standard deviations and 95% confidence intervals. Estimated using the Kaplan-Meier estimator with confidence interval calculated based on the Brookmeyer-Crowley method.

objective response rate
2 years

To assess the effect of the combination of panitumumab and paclitaxel on objective response rate in first-line treatment of metastatic or recurrent squamous cell carcinoma of head and neck (SCCHN).

Overall Response Rate (ORR)
18 months

The Percentage of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

The Number of Participants With Response to GEMOX-Panitumumab (GEMOX-P) in Chemotherapy naïve KRAS/ BRAF Wild Type Stage IV Biliary Tract Cancer Using the Response Evaluation Criteria In Solid Tumors (RECIST) Criteria.
end of cycle 2 of treatment

Tumor measurement - same imaging modality used in pre-treatment evaluation - include radiological examination of all areas with affected disease. For pretreatment and at the end of cycle 2 CT scans (chest/abdomen/pelvis) will be used. For all subsequent cycles, CT of chest/abdomen/pelvis will be used every 8 weeks.

Median Time to Progression (TTP)
18 months

Defined as the time between Day 1-Cycle 1 and date of first documented disease progression assessed using Response Evaluation Criteria in Solid Tumors (RECISTS) v1.1.

Number of Participants With Pathologic Complete Response Following Surgery
Post surgery

Pathologic complete response (pCR) was defined as no viable residual tumor cells. A cellular residual mucin pools should be noted but also considered a pathologic complete response.

Area Under the Curve (AUC) of Total Plasma Cisplatin-derived Platinum Levels With and Without the Presence of Panitumumab
Levels measured at 0.5, 1, 2, 3, 4, 6 and 24 hours following start of cycle 2 cisplatin infusion

AUC refers to area under the concentration curve from time 0 to last measurable concentration. AUC of total plasma cisplatin-derived platinum levels is estimated both for subjects receiving cisplatin with panitumumab and for subjects receiving cisplatin without panitumumab.

Steady-state Plasma Concentrations (Css) for 5-FU With and Without the Presence of Panitumumab
24 to 96 hours following start of cycle 2 infusion with 5-FU

Steady-state plasma concentrations (Css) of 5-FU were estimated as the mean of two or more evaluable concentrations at 24, 72, and 96 hours after the start of 5-FU infusion. Css is estimated both for subjects receiving 5-FU with panitumumab and for subjects receiving 5-FU without panitumumab

Local Regional Control Rate at 2 Years
from study day 1 to 2 years

Kaplan-Meier estimate of Local regional control rate at 2 years. Local regional control rate will be measured according to the investigator's assessment of disease status based on all available data (ie, from clinical examination, radiologic assessments, pathology reports, and autopsy reports).

Progression Free Survival (PFS) During the First-line Treatment Phase
Every 6 weeks until disease progression or death, up to 67 months

The time from the date of randomization to the date of first disease progression determined by the investigators per modified RECIST v1.0, or death within 60 days after the last evaluable tumor assessment or randomization date (whichever is later) during the first-line treatment phase.

Objective Response Rate at Weeks 17 and 25
Week 17 and Week 25

Objective response rate is defined as the percentage of participants with a best response of complete response or partial response. Disease assessments were based on investigator review of scans using modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria. A complete or partial response was confirmed no less than 4 weeks after the criteria for response were first met. Participants with no radiographic tumor assessment(s) at Week 17 or 25 were considered non-responders. Complete Response (CR): disappearance of all target and non-target lesions and no new lesions. Partial Response (PR): At least a 30% decrease in the size of target lesions with no progression of non-target lesions (defined as a ≥ 25% increase in lesion size) and no new lesions, or, the disappearance of all target lesions but persistence of 1 or more non-target lesions not qualifying for either CR or progressive disease (PD) and no new lesions.

Best Response During Second-Line Treatment
Tumor response was assessed at Weeks 9, 17, 25, and 33, and once every 12 weeks thereafter until the end of second-line treatment; maximum time on treatment was 77 weeks.

Objective response rate is defined as the percentage of participants with a best response of complete response or partial response based on investigator review of scans using modified RECIST criteria. A complete or partial response was confirmed no less than 4 weeks after the criteria for response were first met. Participants with no post-baseline radiographic tumor assessment(s) were considered non-responders. CR: disappearance of all target and non-target lesions and no new lesions. PR: At least a 30% decrease in the size of target lesions with no progression of non-target lesions (defined as a ≥ 25% increase in lesion size) and no new lesions, or, the disappearance of all target lesions but persistence of 1 or more non-target lesions not qualifying for either CR or PD and no new lesions.

Progression-free Survival Rate at Weeks 17 and 25
Week 17 and Week 25

The progression-free survival rate is defined as the Kaplan-Meier (KM) estimator of progression-free survival at Week 17 and Week 25 reported as the probability of being event (disease progression or death)-free. Tumor assessments were evaluated by the investigator according to modified RECIST criteria. PD: At least a 20% increase in the size of target lesions since the treatment started or at least a 25% increase in the size of non-target lesions and the lesion(s) measure ≥ 10 mm, or the appearance of any new lesions. Participants who withdraw from the study prior to completion of Week 17 or 25 radiographic tumor assessments were censored at the last evaluable tumor assessment.

Disease Control Rate at Weeks 17 and 25
Week 17 and Week 25

The percentage of participants whose best response was either a complete or partial response or stable disease, based on modified RECIST criteria as assessed by the investigator. Stable diease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD of target lesions and no progression of existing non-target lesions and no new lesions, or, the persistence of 1 or more non-target lesions not qualifying for either CR or PD if no target lesions were identified at Baseline.

Duration of Response
Tumor response was assessed at Weeks 9, 17, 25, and 33, and once every 12 weeks thereafter until the end of second-line treatment; maximum time on treatment was 77 weeks.

Duration of response is defined as the time from the date of first response to the date of first progression of disease during second-line treatment (as evaluated by the investigator) or death (if the death was due to disease progression but not detected earlier) in the subset of participants who responded (CR or PR, as evaluated by the investigator). Duration of response was analyzed using Kaplan-Meier methods; participants who responded but did not progress while on study were censored at the date of last tumor assessment.

Time to Treatment Failure
Tumor response was assessed at Weeks 9, 17, 25, and 33, and once every 12 weeks thereafter until the end of second-line treatment; maximum time on treatment was 77 weeks.

Time to failure of second-line treatment is defined as the time from study Day 1 to the date of the earliest of the following events: end of second-line therapy due to any reason except for complete response and curative surgery; progressive disease; or death due to any cause. Time to treatment failure was analyzed using Kaplan-Meier methods; participants who did not discontinue second-line treatment or discontinue due to complete response or curative surgery, who were still alive, and who did not have disease progression were censored at the date of the last contact.

Time to Progression
From Study Day 1 until the data cut-off date of 2 January 2009; median follow-up time was 39 weeks, with a maximum of 93 weeks.

Time to progression is defined as the time from study Day 1 to the date of observed disease progression. Time to progression was analyzed using Kaplan-Meier methods; participants who did not have disease progression were censored at the date of last evaluable tumor assessment.

Time to Response
Tumor response was assessed at Weeks 9, 17, 25, and 33, and once every 12 weeks thereafter until the end of second-line treatment; maximum time on treatment was 77 weeks.

Time to response of second-line treatment is defined as the time from study Day 1 to the date of first documentation of CR or PR, calculated for those participants with an objective tumor response of CR or PR.

Percentage of Participants With Specific Grade 2 or Higher Skin Toxicities During the 6-week Skin Treatment Period
6 weeks

Skin toxicities were assessed by the study clinician and graded according to the modified Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0 Dermatology Toxicity Grading criteria, on a scale from Grade 1 (mild) to 4 (life-threatening). The specific skin toxicities of interest were pruritus, acneiform dermatitis, skin desquamation (also described as skin exfoliation), exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection.

Objective Tumor Response Through Week 16
From enrollment through Week 16

Confirmed objective tumor response was defined as a complete response or partial response from enrollment through Week 16. Tumor response was monitored, beginning at Week 8, per a modified version of the World Health Organization (WHO) criteria for tumor response and progression by an independent review committee central assessment. Complete response was defined per modified WHO criteria as disappearance of all lesions (index and non-index). Partial response was defined as ≥ 50% decrease from Baseline in the sum of the products of the longest diameters (SPD) of index lesions. Scans were required to confirm a complete or partial response no earlier than 4 weeks from the time a response of complete or partial response was first documented.

To provide continued, extended panitumumab treatment to subjects who appeared to have benefited from and tolerated previous panitumumab treatment in Studies 20020374 Part 2 or 20030138 and its extension study, 20040116
Until disease progression, an AE or withdrawn consent
Number of Participants With Objective Tumor Response Through Week 16
16 weeks

Confirmed objective tumor response (complete or partial response) based on modified World Health Organization (WHO) criteria, through week 16. Tumor response was assessed by a central Independent Review Committee (IRC) and confirmation 4 weeks after initial assessment was required. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the sum of the product of the longest diameters (SPD) of index lesions taking as reference the Baseline SPD, and no new non-index lesions and no "unequivocal progression" of non-index lesions, or, the disappearance of all index lesions and persistence of one or more non-index lesions not qualifying for either CR or Progressive Disease.

Part 2, Cohort 1: Efficacy: Tumor response rate (CR or PR) measured at 8 weeks
Part 2, Cohort 1: Safety: Incidence and severity of AEs
Part 2, Cohort 2: Time to disease progression
Number of Participants With Grade 3 or Grade 4 Diarrhea (Part 2)
Until disease progression (median 47 weeks)

The number of participants with grade 3 or grade 4 diarrhea in Part 2 of the study. Grading of diarrhea followed the grading scale in Version 2.0 of the National Cancer Institute Common Toxicity Criteria (NCI CTC).

Number of Participants With Grade 3 or Grade 4 Diarrhea (Part 1)
Until disease progression (median 35 weeks) or 48 weeks, whichever occurred first

The number of participants with grade 3 or grade 4 diarrhea in Part 1 of the study. Grading of diarrhea followed the grading scale in Version 2.0 of the National Cancer Institute Common Toxicity Criteria (NCI CTC).

Maximum Observed Plasma Concentration (Cmax) of Irinotecan
Predose and at 10 minutes, and 0.5, 1, 2, 4, 8, 24, 48, and 72 hours after the end of the irinotecan infusion at cycle 1 (irinotecan alone, week 1 day 1) and cycle 2 (irinotecan with panitumumab, week 3, day 1).

To analyze the effect, if any, that panitumumab had on the pharmacokinetics of irinotecan, the Cmax of irinotecan administered alone (Cycle 1) and with concomitant panitumumab (Cycle 2) was measured. Plasma samples were assayed by a validated high performance liquid chromatography (HPLC)-fluorescence method for the measurement of irinotecan. The lower limit of quantitation (LLOQ) was 2 ng/mL.

Area Under the Plasma Concentration-time Curve From the Time of Dosing to Infinity (AUCinf) for Irinotecan
Predose and at 10 minutes, and 0.5, 1, 2, 4, 8, 24, 48, and 72 hours after the end of the irinotecan infusion at cycle 1 (irinotecan alone, week 1 day 1) and cycle 2 (irinotecan with panitumumab, week 3, day 1).

To analyze the effect, if any, that panitumumab had on the pharmacokinetics of irinotecan, the AUCinf of irinotecan administered alone (Cycle 1) and with concomitant panitumumab (Cycle 2) was measured.

Area Under the Plasma Concentration-time Curve From the Time of the Last Quantifiable Concentration (AUClast) for Irinotecan
Predose and at 10 minutes, and 0.5, 1, 2, 4, 8, 24, 48, and 72 hours after the end of the irinotecan infusion at cycle 1 (irinotecan alone, week 1 day 1) and cycle 2 (irinotecan with panitumumab, week 3, day 1).

To analyze the effect, if any, that panitumumab had on the pharmacokinetics of irinotecan, the AUClast of irinotecan administered alone (Cycle 1) and with concomitant panitumumab (Cycle 2) was measured.

Number of Participants With Clinically Significant Adverse Events (AEs)
The reporting time frame for Adverse Events is from first dose date to 30 days since the last dose date, until the data cut-off date of 16 July 2009. The median time frame is 5.7 months.

Adverse events of special interest include infusion reactions, integument toxicities, diarrhea, stomatitis, hypomagnesemia, and pulmonary, vascular, and cardiac toxicities. Infusion reactions were defined as 1. Prespecified signs and symptoms indicating a possible infusion reaction (derived from Common Terminology Criteria for Adverse Events (CTCAE) definitions of allergic reaction/hypersensitivity and cytokine release syndrome/acute infusion reaction) with onset day coincident with any study drug infusion and which resolved the day of, or the day after, onset; 2. incidence of AE with terms consistent with the panitumumab US package insert (USPI) (any event within 24 hours of an infusion during the clinical study described as allergic reaction or anaphylactoid reaction, or any event occurring on the first day of dosing described as allergic reaction, anaphylactoid reaction, fever, chills, or dyspnea). Data are summarized overall and by treatment phase.

Number of Participants With Dose-limiting Toxicities (DLTs)
28 days from initial administration of panitumumab for the 2.5 and 6 mg/kg cohorts and 21 days from first administration for the 9 mg/kg cohort.

Any panitumumab related grade 3 or 4 hematologic or non-hematologic toxicity (graded according to the modified Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria) was considered a DLT with the exception of alopecia and fatigue. Hypomagnesemia, nausea, diarrhea, vomiting, and skin or nail toxicities constituted a DLT only of the following occured: • Grade 3 or 4 hypomagnesemia that persisted for at least 5 days despite maximal magnesium replacement; • Grade 3 or 4 diarrhea, nausea, or vomiting that persisted for at least 5 days despite maximum supportive therapy; • Grade 4 skin or nail toxicity.

Number of Participants With Adverse Events (AEs)
From first dose date to end of study date. The median duration of study was 47 days.

A serious adverse event is defined as an AE that: • is fatal; • is life threatening; • requires in-patient hospitalization or prolongation of existing hospitalization; • results in persistent or significant disability/incapacity; • is a congenital anomaly/birth defect; • other significant medical hazard. The investigator assessed whether adverse events were related to panitumumab. The severity of adverse events was based on CTCAE version 3 (with the exception of skin- or nail-related toxicities which were graded using the CTCAE version 3.0 with modifications), according to the following: Grade 1 = Mild (aware of sign or symptom, but easily tolerated); Grade 2 = Moderate (discomfort enough to cause interference with usual activity); Grade 3 = Severe (incapacitating with inability to work or do usual activity); Grade 4 = Life-threatening or disabling; Grade 5 = Fatal.

Maximum Observed Concentration (Cmax) of Panitumumab
First dose (Day 1) and third dose (Day 15/29/43 for the QW, Q2W and Q3W cohorts respectively). Samples were collected over the dosing interval for each treatment cohort (7, 14 or 21 days for QW, Q2W and Q3W cohorts respectively).

Panitumumab serum concentration was measured using an enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) of the assay was 400 pg/mL. Concentrations below the LLOQ were set to zero.

Minimum Observed Concentration (Cmin) of Panitumumab
First dose (Day 1) and third dose (Day 15/29/43 for the QW, Q2W and Q3W cohorts respectively). Samples were collected over the dosing interval for each treatment cohort (7, 14 or 21 days for QW, Q2W and Q3W cohorts respectively).
Area Under the Concentration-time Curve During the Dosing Interval (AUC0-tau) for Panitumumab
First dose (Day 1) and third dose (Day 15/29/43 for the QW, Q2W and Q3W cohorts respectively). Samples were collected over the dosing interval for each treatment cohort (7, 14 or 21 days for QW, Q2W and Q3W cohorts respectively).

The area under the serum concentration-time curve from time zero to the end of the dosing interval (AUCtau), estimated using the linear trapezoidal method.

Half-life (t1/2) for the Terminal Phase (First Dose) or Dosing Interval (Third Dose) of Panitumumab
First dose (Day 1) and third dose (Day 15/29/43 for the QW, Q2W and Q3W cohorts respectively). Samples were collected over the dosing interval for each treatment cohort (7, 14 or 21 days for QW, Q2W and Q3W cohorts respectively).
Serum Clearance (CL) of Panitumumab
First dose (Day 1) and third dose (Day 15/29/43 for the QW, Q2W and Q3W cohorts respectively). Samples were collected over the dosing interval for each treatment cohort (7, 14 or 21 days for QW, Q2W and Q3W cohorts respectively).
Part 1: Number of Participants With Dose-limiting Toxicities
4 weeks

A dose-limiting toxicity (DLT) was defined as any grade 3 or 4 conatumumab-related or combination (panitumumab and conatumumab)-related adverse event, or grade 3 or 4 laboratory abnormality that occurred during the first 4 weeks (28 days) of treatment with panitumumab and conatumumab. Anemia and lymphopenia were not considered DLTs. Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used to grade all adverse events and toxicities.

Number of Participants With an Objective Response
Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).

An overall objective response of either a confirmed complete response or partial response, where the overall objective response was equivalent to the best overall response recorded for each participant from enrollment until disease progression or recurrence. Tumor response was assessed by the investigator according to the modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Responses were confirmed no less than 4 weeks after the criteria for response were first met. Complete response defined as the disappearance of all target and non-target lesions and no new lesions. Partial response defined as either the disappearance of all target lesions with the persistence of one or more non-target lesion(s), or, at least a 30% decrease in the sum of the longest diameter (SLD) of target lesions, taking as reference the Baseline SLD and the disappearance of all or the persistence of 1 or more non-target lesions.

Time to Maximum Plasma Concentration of Motesanib (Tmax) for Cycle 1
Cycle 1, Day 3 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

The time after dosing that the maximal plasma concentration of motesanib was observed in Cycle 1. For the 75 mg BID cohorts, Tmax is reported for the first daily dose.

Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 1
Cycle 1, Day 3 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

The maximal observed plasma concentration of motesanib after a single dose dose in Cycle 1. For the 75 mg BID cohorts, Cmax is reported for the first daily dose.

Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 1
Cycle 1, Day 3 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours postdose.

The terminal-phase elimination half-life (t1/2,z) of motesanib was calculated as ln(2)/λz. The terminal elimination rate constant (λz) was determined by linear regression of the natural logarithms of at least the last 3 measurable concentrations during the terminal phase. For the 75 mg BID cohorts, t1/2,z is reported for the first daily dose.

Area Under the Plasma Concentration-time Curve for Motesanib in Cycle 1
Cycle 1, Day 3 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

Area under the plasma concentration-time curve for motesanib in Cycle 1 calculated using the using the linear/log trapezoidal method. AUC from time zero to infinity (AUC0-inf) is reported for the 50 and 125 mg QD cohorts and AUC from time 0 to 24 hours post-dose (AUC0-24) is reported for the 75 mg BID cohort, where AUC0-24 is the sum of AUC0-12 for the first and second daily dose.

Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 1
Cycle 1, Day 3, 24 hours post-dose

The trough plasma concentration for motesanib at 24 hours postdose in Cycle 1. For the 75 BID cohort, C24 is the observed concentration at 24 hours (ie, after the second daily dose).

Time to Maximum Plasma Concentration of Motesanib (Tmax) in Cycle 2
Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

The time after dosing that the maximal plasma concentration of motesanib was observed in Cycle 2. For the 75 mg BID cohorts, Tmax is reported for the first daily dose.

Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 2
Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

The maximal observed plasma concentration of motesanib in Cycle 2, after multiple doses. For the 75 mg BID cohorts, Cmax is reported for the first daily dose.

Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 2
Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

The terminal-phase elimination half-life (t1/2,z) of motesanib was calculated as ln(2)/λz. The terminal elimination rate constant (λz) was determined by linear regression of the natural logarithms of at least the last 3 measurable concentrations during the terminal phase. For the 75 mg BID cohorts, t1/2,z is reported for the first daily dose.

Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for Motesanib in Cycle 2
Cycle 2, Day 1 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) for motesanib in Cycle 2 calculated using the using the linear/log trapezoidal method. For the 75 mg BID cohort AUC0-24 is the sum of AUC0-12 for the first and second daily dose.

Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 2
Cycle 2, Day 1, 24 hours post-dose

The trough plasma concentration for motesanib at 24 hours postdose in Cycle 2. For the 75 BID cohort, C24 is the observed concentration at 24 hours (ie, after the second daily dose).

To evaluate the safety and PK of 2 dose schedules of panitumumab in subjects with advanced solid tumors, refractory to or with no available standard therapy.
2 years
Secondary Endpoints
Progression-free Survival
From randomization to the last on-study or long-term follow-up visit, as of the data cut-off date of 10 June 2014. The median follow-up time was 34.9 weeks (panitumumab plus BSC: 41.0 weeks; BSC alone: 25.5 weeks).
Overall Survival in Participants With Wild-type RAS
From randomization to the last on-study or long-term follow-up visit, as of the data cut-off date of 10 June 2014. The median follow-up time was 36.1 weeks (panitumumab plus BSC: 43.7 weeks; BSC alone: 23.6 weeks).
Progression Free Survival (PFS) in Participants With Wild-type RAS
From randomization to the last on-study or long-term follow-up visit, as of the data cut-off date of 10 June 2014. The median follow-up time was 36.1 weeks (panitumumab plus BSC: 43.7 weeks; BSC alone: 23.6 weeks).
Unlock Study Endpoints
Study Design & Arms
AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Panitumumab + BSCEXPERIMENTALParticipants received panitumumab administered intravenously 6 mg/kg every 14 days plus BSC until disease progression, withdrawal of consent, death, or intolerance of study drug.
BSC AloneOTHERParticipants received best supportive care until disease progression, withdrawal of consent, or death.
CetuximabACTIVE_COMPARATORCetuximab 400 mg/m\^2 as an initial dose, followed by 250 mg/m\^2 intravenously (IV) every 7 days. Participants were treated until disease progression, intolerability, withdrawal of consent, or death.
PanitumumabEXPERIMENTALPanitumumab 6 mg/kg IV every 14 days. Participants were treated until disease progression, intolerability, withdrawal of consent, or death.
FOLFOX + PanitumumabEXPERIMENTALParticipants received panitumumab, 6 mg/kg on Day 1 and FOLFOX chemotherapy regimen on Days 1 and 2 of each 14-day cycle until disease progression or unacceptable toxicity.
FOLFOXACTIVE_COMPARATORParticipants received FOLFOX chemotherapy regimen on Days 1 and 2 of each 14-day cycle until disease progression or until unacceptable toxicity.
Panitumumab Plus FOLFIRIEXPERIMENTALParticipants received panitumumab as an intravenous (IV) infusion at a dose of 6 mg/kg plus a standard chemotherapy regimen (FOLFIRI) consisting of 5-fluorouracil (5-FU), leucovorin and irinotecan. Treatment was administered in cycles every two weeks.
FOLFIRI AloneACTIVE_COMPARATORParticipants received standard chemotherapy regimen (FOLFIRI) consisting of 5-FU, leucovorin and irinotecan. Treatment is administered in cycles every two weeks.
Oxaliplatin and bevacizumab without panitumumabACTIVE_COMPARATOROxaliplatin-based chemotherapy and Bevacizumab Q2W alone.
Irinotecan and bevacizumab plus panitumumabEXPERIMENTALIrinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6mg/kg Q2W
Irinotecan and bevacizumab without panitumumabACTIVE_COMPARATORIrinotecan-based chemotherapy and Bevacizumab Q2W alone
Oxaliplatin and bevacizumab plus panitumumabEXPERIMENTALOxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6mg/kg Q2W
Panitumumab plus best supportive careEXPERIMENTALPanitumumab will be administered by intravenous infusion at a dose of 6 mg/kg once every 2 weeks until participants develop progressive disease or are unable to tolerate study drug. Participants will also receive best supportive care (BSC) as judged appropriate by the investigator and according to institutional guidelines.
Best Supportive CareOTHERBest supportive care will be defined in this study as the best care available as judged appropriate by the investigator and according to institutional guidelines and will include antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any symptomatic therapy as clinically indicated. For the purpose of this study, best supportive care will not include anti-neoplastic chemotherapy.
RAS mutations frequency <= 7%OTHERPanitumumab 6 mg/kg BW as 60-min i.v. infusion\* D1 \*If the 1st infusion is well tolerated, all subsequent infusions can be applied over 30-60 minutes. Followed by FOLFIRI regimen * Irinotecan 180 mg/m² BSA i.v., 30 - 90 min D1 * Folinic acid (racemic) 400 mg/m²BSA i.v., 120 min D1 * 5-FU 400 mg/m² BSA, bolus, D1 * 5-FU 2400 mg/m² BSA i.v. infusion over a period of 46 h D1-2 q day 14
RAS mutation frequency >7% to <=14%OTHERPanitumumab 6 mg/kg BW as 60-min i.v. infusion\* D1 \*If the 1st infusion is well tolerated, all subsequent infusions can be applied over 30-60 minutes. Followed by FOLFIRI regimen * Irinotecan 180 mg/m² BSA i.v., 30 - 90 min D1 * Folinic acid (racemic) 400 mg/m²BSA i.v., 120 min D1 * 5-FU 400 mg/m² BSA, bolus, D1 * 5-FU 2400 mg/m² BSA i.v. infusion over a period of 46 h D1-2 q day 14
RAS mutation frequency >14% to <=20%OTHERPanitumumab 6 mg/kg BW as 60-min i.v. infusion\* D1 \*If the 1st infusion is well tolerated, all subsequent infusions can be applied over 30-60 minutes. Followed by FOLFIRI regimen * Irinotecan 180 mg/m² BSA i.v., 30 - 90 min D1 * Folinic acid (racemic) 400 mg/m²BSA i.v., 120 min D1 * 5-FU 400 mg/m² BSA, bolus, D1 * 5-FU 2400 mg/m² BSA i.v. infusion over a period of 46 h D1-2 q day 14
FOLFIRI + panitumumabEXPERIMENTALAll patients will receive panitumumab plus FOLFIRI for disease control in 14-day cycles until disease progression, unacceptable toxicity, investigator's decision or patient withdrawal of consent, at the following doses: * Panitumumab: 6 mg/kg administered by intravenous (IV) infusion over 60 min on days 1 and 14 of every cycle just before administration of chemotherapy * FOLFIRI * Irinotecan: 150 mg/m2 as IV infusion over 90 min on day 1of first treatment cycle. If tolerance of this first dose is good, it will be scaled to a full dose of 180 mg/m2 starting from the second treatment cycle. * Folinic acid: (leucovorin) 200-400 mg/m2 IV over 2 hours on day 1 * 5-FU: 400 mg/m2 bolus followed by 2400 mg/m2 IV continuous infusion over 46-48 hours on days 1 and 2
Panitumumab + FOLFOX (DP)EXPERIMENTALPanitumumab and FOLFOX will be administered to patients with DP (MMP7+/p-IGF-IR) once every 14 days until 6 months of treatment or until disease progression (PD) or unacceptable toxicity. If patients have not progressed after 6 months of treatment with panitumumab and FOLFOX they will continue with panitumumab monotherapy until disease progression.
Panitumumab + FOLFOX (no-DP)EXPERIMENTALPanitumumab and FOLFOX will be administered to patients with no-DP (MMP7+/p-IGF-IR-, MMP7-/p-IGF-IR+ or MMP7-/p-IGF-IR) once every 14 days until 6 months of treatment or until disease progression (PD) or unacceptable toxicity. If patients have not progressed after 6 months of treatment with panitumumab and FOLFOX they will continue with panitumumab monotherapy until disease progression.
Panitumumab/Gemcitabine/CarboplatinEXPERIMENTALSystemic therapy
Arm A: Erlotinib + Panitumumab + IrinotecanEXPERIMENTALPatients receive oral erlotinib hydrochloride once daily on days 1-14, panitumumab IV over 30-90 minutes on day 1, and irinotecan hydrochloride IV over 90 minutes on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
Arm B: Erlotinib + PanitumumabEXPERIMENTALPatients receive oral erlotinib hydrochloride once daily on days 1-14 and panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. Upon disease progression, patients receive irinotecan hydrochloride as in arm A.
Arm C: Erlotinib + PanitumumabEXPERIMENTALPatients receive erlotinib hydrochloride and panitumumab as in arm B.
Irinotecan plus panitumumabEXPERIMENTALIrinotecan 100 mg/m2 IV Day 1 and Day 8 \+ Panitumumab 9mg/kg IV Day 1 Cycle = 21 days
OlaparibEXPERIMENTALOlaparib for patients with a molecular tumor profile that can potentially be targeted by Olaparib.
DabrafenibEXPERIMENTALDabrafenib for patients with a molecular tumor profile that can potentially be targeted by Dabrafenib.
NilotinibEXPERIMENTALNilotinib for patients with a molecular tumor profile that can potentially be targeted by nilotinib.
TrametinibEXPERIMENTALTrametinib for patients with a molecular tumor profile that can potentially be targeted by trametinib.
ErlotinibEXPERIMENTALErlotinib for patients with a molecular tumor profile that can potentially be targeted by erlotinib.
Trastuzumab & Pertuzumab (combination)EXPERIMENTALTrastuzumab and Pertuzumab (combination treatment) for patients with a molecular tumor profile that can potentially be targeted by Trastuzumab and Pertuzumab.
Vemurafenib & Cobimetinib (combination)EXPERIMENTALVemurafenib and Cobimetinib (combination treatment) for patients with a molecular tumor profile that can potentially be targeted by Vemurafenib and Cobimetinib.
VismodegibEXPERIMENTALVismodegib for patients with a molecular tumor profile that can potentially be targeted by vismodegib.
RegorafenibEXPERIMENTALRegorafenib for patients with a molecular tumor profile that can potentially be targeted by regorafenib.
NivolumabEXPERIMENTALNivolumab for patients with a molecular tumor profile that can potentially be targeted by nivolumab.
AfatinibEXPERIMENTALAfatinib for patients with a molecular tumor profile that can potentially be targeted by Afatinib.
Dabrafenib & trametinib (combination)EXPERIMENTALDabrafenib and trametinib (combination treatment) for patients with a molecular tumor profile that can potentially be targeted by Dabrafenib and trametinib.
RibociclibEXPERIMENTALRibociclib for patients with a molecular tumor profile that can potentially be targeted by Ribociclib.
LenvatinibEXPERIMENTALLenvatinib for patients with a molecular tumor profile that can potentially be targeted by Lenvatinib.
PembrolizumabEXPERIMENTALPembrolizumab for patients with a molecular tumor profile that can potentially be targeted by Pembrolizumab.
DurvalumabEXPERIMENTALDurvalumab for patients with a molecular tumor profile that can potentially be targeted by Durvalumab.
RucaparibEXPERIMENTALRucaparib for patients with a molecular tumor profile that can potentially be targeted by Rucaparib.
AxitinibEXPERIMENTALAxitinib for patients with a molecular tumor profile that can potentially be targeted by Axitinib.
PalbociclibEXPERIMENTALPalbociclib for patients with a molecular tumor profile that can potentially be targeted by Palbociclib.
CrizotinibEXPERIMENTALCrizotinib for patients with a molecular tumor profile that can potentially be targeted by Crizotinib.
SunitinibEXPERIMENTALSunitinib for patients with a molecular tumor profile that can potentially be targeted by Sunitinib.
CabozantinibEXPERIMENTALCabozantinib for patients with a molecular tumor profile that can potentially be targeted by Cabozantinib.
AbemaciclibEXPERIMENTALAbemaciclib for patients with a molecular tumor profile that can potentially be targeted by Abemaciclib.
AlectinibEXPERIMENTALAlectinib for patients with a molecular tumor profile that can potentially be targeted by Alectinib.
Atezolizumab/bevacizumabEXPERIMENTALAtezolizumab and bevacizumab (combination treatment) for patients with a molecular tumor profile that can potentially be targeted by Atezolizumab and bevacizumab.
Ipilimumab/nivolumabEXPERIMENTALIpilimumab and nivolumab (combination treatment) for patients with a molecular tumor profile that can potentially be targeted by Ipilimumab and nivolumab.
EntrectinibEXPERIMENTALEntrectinib for patients with a molecular tumor profile that can potentially be targeted by entrectinib.
TalazoparibEXPERIMENTALTalazoparib for patients with a molecular tumor profile that can potentially be targeted by talazoparib.
dacomitinibEXPERIMENTALDacomitinib for patients with a molecular tumor profile that can potentially be targeted by dacomitinib.
LorlatinibEXPERIMENTALLorlatinib for patients with a molecular tumor profile that can potentially be targeted by lorlatinib.
ErdafitinibEXPERIMENTALErdafitinib for patients with a molecular tumor profile that can potentially be targeted by erdafitinib.
AlpelisibEXPERIMENTALAlpelisib for patients with a molecular tumor profile that can potentially be targeted by alpelisib.
NiraparibEXPERIMENTALNiraparib for patients with a molecular tumor profile that can potentially be targeted by niraparib.
PemigatinibEXPERIMENTALPemigatinib for patients with a molecular tumor profile that can potentially be targeted by pemigatinib.
SelpercatinibEXPERIMENTALSelpercatinib for patients with a molecular tumor profile that can potentially be targeted by selpercatinib.
TepotinibEXPERIMENTALTepotinib for patients with a molecular tumor profile that can potentially be targeted by tepotinib.
Treatment (panitumumab, combination chemotherapy)EXPERIMENTAL5-Fluorouracil, irinotecan, and panitumumab
Panitumumab + PaclitaxelEXPERIMENTALTreatment consisted of intravenous panitumumab 6 mg/kg q2w, administered in one hour the first day and in 30 minutes thereafter (if no infusional reaction was observed) plus intravenous paclitaxel 80 mg/m2 weekly administered one hour after panitumumab in one hour infusion, until progression or unacceptable toxicity. Panitumumab does not require prophylactic premedication from the first infusion. Paclitaxel was administered with: dexamethasone 10 mg, diphenhydramine 30 mg and antiH2 (cimetidine 300 mg or ranitidine 50 mg). Dose modifications of paclitaxel included 4.8 mg/kg (80% of the initial dose) and 3.6 mg/kg (60%) when recovered from a grade 3-4 skin toxicity to grade ≤2. Continuing paclitaxel on the day of the planned infusion required no grade ≥2 mucositis and hematologic recovery with an absolute neutrophil count ≥1,500/ml and a platelet count ≥75,000.
FOLFOXIRI+panitumumab regimenEXPERIMENTALAll patients will receive the FOLFOXIRI/panitumumab regimen, with drugs administered in the following order: * Panitumumab * Oxaliplatin * Irinotecan * Leucovorin * 5-Fluorouracil
Carboplatin/Pemetrexed/PanitumumabEXPERIMENTALSystemic Therapy
Panitumumab Plus mFOLFOX6EXPERIMENTALParticipants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and modified FOLFOX6 (mFOLFOX6) chemotherapy regimen consisting of oxaliplatin (85 mg/m\^2), leucovorin (400 mg/m\^2) and 5-fluorouracil (5-FU) (2400 mg/m\^2) administered on Day 1 of every 14-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death.
Bevacizumab Plus mFOLFOX6ACTIVE_COMPARATORParticipants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 regimen consisting of oxaliplatin (85 mg/m\^2), leucovorin (400 mg/m\^2), followed by 5-FU (2400 mg/m\^2) administered on Day 1 of every 14-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death.
Docetaxel + Cisplatin + Panitumumab + RTOTHERPatients received docetaxel (40 mg/m\^2), cisplatin (40 mg/m\^2) and panitumumab (6 mg/kg) on weeks 1, 3, 5, 7, and 9 with radiotherapy (RT) (5040 cGy, 180 cGy/day x 28 days) beginning week 5. Resection was planned after completing chemotherapy (CRT).
Panitumumab plus ChemotherapyACTIVE_COMPARATORSubjects receiving cisplatin and 5/FU and receiving Panitumumab who have with Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck
Chemotherapy AloneACTIVE_COMPARATORSubjects receiving cisplatin and 5/FU and not receiving Panitumumab who have with Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck
ARM 1 CRTACTIVE_COMPARATORCisplatin plus RT
ARM 2 PRTEXPERIMENTALPanitumumab plus RT
Panitumumab Plus ChemoradiationEXPERIMENTALParticipants received standard radiation therapy for 7 weeks and cisplatin 75 mg/m\^2 and panitumumab 9 mg/kg on Days 1, 22 and 43.
Chemoradiotherapy AloneACTIVE_COMPARATORParticipants received standard radiation therapy for 7 weeks and cisplatin 100 mg/m\^2 on Days 1, 22, and 43.
Arm 1EXPERIMENTALPanitumumab + Docetaxel + Cisplatin
Arm 2OTHERcontrol
Arm AEXPERIMENTALFOLFIRI + Panitumumab
Arm BEXPERIMENTALFOLFIRI + Bevacizumab
Pre-emptive Skin TreatmentEXPERIMENTALParticipants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy.
Reactive Skin TreatmentEXPERIMENTALParticipants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required.
Open LabelEXPERIMENTALDose received in previous studies will be rolled over to this study. These regimens include: 2.5 mg/kg weekly; 6.0 mg/kg every 2 weeks; and 9.0 mg/kg every 3 weeks.
Part 1: Panitumumab + IFLEXPERIMENTALPanitumumab (2.5 mg/kg once weekly for up to 48 weeks or until disease progression, intolerable adverse event or other reason for discontinuation) in combination with irinotecan, 5-fluorouracil (5-FU)and leucovorin (IFL chemotherapy regimen)
Part 2: Panitumumab + FOLFIRIEXPERIMENTALPanitumumab (2.5 mg/kg once weekly until disease progression, intolerable adverse event or other reason for discontinuation) in combination with irinotecan/5-FU/leucovorin chemotherapy (the FOLFIRI regimen)
Panitumumab + IrinotecanEXPERIMENTALParticipants received panitumumab 6 mg/kg and irinotecan 180 mg/m² administered by intravenous (IV) infusion every 2 weeks until disease progression or intolerance of panitumumab, irinotecan or both.
Panitumumab plus conatumumabEXPERIMENTALParticipants received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.
Paclitaxel + Carboplatin + MotesanibEXPERIMENTALChemotherapy naïve participants received paclitaxel 200 mg/m\^2 and carboplatin chemotherapy administered by intravenous (IV) infusion on Day 1 of each 21-day cycle, and motesanib, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. The initial dose of motesanib was 50 mg once daily administered in the initial cohort and up to 125 mg once daily was used in subsequent cohorts. A cycle was defined as the 3 weeks plus the time to recover from toxicity, if encountered.
Panitumumab + MotesanibEXPERIMENTALParticipants with no more than one prior chemotherapy regimen for NSCLC received panitumumab administered by IV at 9.0 mg/kg on Day 1 of each 21-day cycle, and motesanib, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. The initial dose of motesanib was 50 mg once daily administered in the initial cohort, up to 125 mg once daily was used in subsequent cohorts.
Panitumumab + Paclitaxel + Carboplatin + MotesanibEXPERIMENTALChemotherapy naïve participants received panitumumab administered by IV at 9.0 mg/kg on Day 1 of each 21-day cycle, paclitaxel 200 mg/m\^2 and carboplatin chemotherapy administered by IV infusion on Day 1 of each 21-day cycle, and motesanib, orally self-administered on Days 3-21 of Cycle 1 and then on Days 1 to 21 of Cycle 2 and all cycles thereafter. Participants were enrolled in this arm once a safe and tolerable dose of motesanib was established.
Cohort 1EXPERIMENTAL6mg/kg of panitumumab administered once every 2 weeks until subjects develop disease progression or are unable to tolerate the study drug
Cohort 2EXPERIMENTALPanitumumab 9 mg/kg administered once every 3 weeks until subjects develop disease progression or are unable to tolerate the study drug.
Interventions
NameTypeDescription
Best Supportive Care (BSC)OTHERBSC was defined as the best palliative care available as judged appropriate by the investigator and according to institutional guidelines and could include antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any other symptomatic therapy as clinically indicated.
PanitumumabDRUGAdministered intravenously
CetuximabDRUGAdministered by intravenous infusion
FOLFOX regimenDRUGThe FOLFOX regimen consisted of oxaliplatin 85 mg/m\^2 intravenous (IV) infusion on Day 1, leucovorin, 200 mg/m\^2 (racemate) on Days 1 and 2 and 5-fluorouracil 400 mg/m\^2 IV bolus followed by 600 mg/m\^2 IV infusion over 22 hours on Days 1 and 2. Each cycle was 14 days.
FOLFIRIDRUGFOLFIRI chemotherapy was initiated on Day 1 of each treatment cycle at the following starting doses: irinotecan 180 mg/m\^2, leucovorin 400 mg/m\^2 racemate (or 200 mg/m\^2 I-leucovorin), 5-FU bolus 400 mg/m\^2, 5-FU infusion 2400 mg/m\^2.
Oxaliplatin Based ChemotherapyDRUGOxaliplatin-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) consisting of Oxaliplatin, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.
Irinotecan Based ChemotherapyDRUGIrinotecan-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) - Irinotecan, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.
BevacizumabDRUGBevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .
Best supportive careOTHERBest supportive care as site routine excluding: antineoplastic chemotherapy, investigational agents, anti-EGFr(Epidermal growth factor receptor) targeting agents other than ABX-EGF(Panitumumab), experimental or approved anti-tumor therapies (e.g. Avastin), chemotherapy, radiotherapy (with the exception of radiotherapy for pain control limited to bone metastases).
IrinotecanDRUGIrinotecan 180 mg/m² BSA i.v., 30 - 90 min D1
Folinic acidDRUGFolinic acid (racemic) 400 mg/m²BSA i.v., 120 min D1
5-FUDRUG5-FU 400 mg/m² BSA, bolus, D1 5-FU 2400 mg/m² BSA i.v. infusion over a period of 46 h D1-2
Panitumumab + FOLFOX (DP)DRUGPanitumumab and FOLFOX will be administered to patients with DP once every 14 days until 6 months of treatment or until disease progression (PD) or unacceptable toxicity. If patients have not progressed after 6 months of treatment with panitumumab and FOLFOX they will continue with panitumumab monotherapy until disease progression.
Panitumumab + FOLFOX (no-DP)DRUGPanitumumab and FOLFOX will be administered to patients with no-DP (MMP7+/p-IGF-IR-, MMP7-/p-IGF-IR+ or MMP7-/p-IGF-IR) once every 14 days until 6 months of treatment or until disease progression (PD) or unacceptable toxicity. If patients have not progressed after 6 months of treatment with panitumumab and FOLFOX they will continue with panitumumab monotherapy until disease progression.
CarboplatinDRUGAUC=2.5 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)
GemcitabineDRUG1500 mg/m2 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)
erlotinib hydrochlorideDRUGGiven orally 150mg daily
irinotecan hydrochlorideDRUGGiven intravenously 120mg/m2 for 6/6 genotype and 60mg/m2 for 6/7 genotype
OlaparibDRUGOlaparib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of olaparib might be expected based on their molecular tumor profile.
DabrafenibDRUGDabrafenib treatment for patients with an mutated advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of dabrafenib might be expected based on their molecular tumor profile.
NilotinibDRUGNilotinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of nilotinib might be expected based on their molecular tumor profile.
TrametinibDRUGTrametinib treatment for patients with an mutated advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of trametinib might be expected based on their molecular tumor profile.
ErlotinibDRUGErlotinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of erlotinib might be expected based on their molecular tumor profile.
Trastuzumab and Pertuzumab (combination treatment)DRUGTrastuzumab and Pertuzumab treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of trastuzumab + pertuzumab might be expected based on their molecular tumor profile.
Vemurafenib and Cobimetinib (combination treatment)DRUGVemurafenib + Cobimetinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Vemurafenib + Cobimetinib might be expected based on their molecular tumor profile.
VismodegibDRUGVismodegib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of vismodegib might be expected based on their molecular tumor profile.
RegorafenibDRUGRegorafenib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of vismodegib might be expected based on their molecular tumor profile.
NivolumabDRUGNivolumab treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of nivolumab might be expected based on their molecular tumor profile.
AfatinibDRUGAfatinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Afatinib might be expected based on their molecular tumor profile.
Dabrafenib and trametinibDRUGDabrafenib + trametinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Dabrafenib + Trametinib might be expected based on their molecular tumor profile.
RibociclibDRUGRibociclib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Ribociclib might be expected based on their molecular tumor profile.
LenvatinibDRUGLenvatinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Lenvatinib might be expected based on their molecular tumor profile.
PembrolizumabDRUGPembrolizumab treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Pembrolizumab might be expected based on their molecular tumor profile.
DurvalumabDRUGDurvalumab treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Durvalumab might be expected based on their molecular tumor profile.
RucaparibDRUGRucaparib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Rucaparib might be expected based on their molecular tumor profile.
AxitinibDRUGAxitinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Axitinib might be expected based on their molecular tumor profile.
PalbociclibDRUGPalbociclib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Palbociclib might be expected based on their molecular tumor profile.
CrizotinibDRUGCrizotinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Crizotinib might be expected based on their molecular tumor profile.
SunitinibDRUGSunitinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Sunitinib might be expected based on their molecular tumor profile.
CabozantinibDRUGCabozantinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Cabozantinib might be expected based on their molecular tumor profile.
AbemaciclibDRUGAbemaciclib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Abemaciclib might be expected based on their molecular tumor profile.
AlectinibDRUGAlectinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Alectinib might be expected based on their molecular tumor profile.
Atezolizumab and BevacizumabDRUGAtezolizumab + Bevacizumab treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Atezolizumab + Bevacizumab might be expected based on their molecular tumor profile.
Ipilimumab and nivolumabDRUGIpilimumab+nivolumab treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of ipilimimab + nivolumab might be expected based on their molecular tumor profile.
EntrectinibDRUGEntrectinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of entrectinib might be expected based on their molecular tumor profile.
TalazoparibDRUGTalazoparib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of talazoparib might be expected based on their molecular tumor profile.
DacomitinibDRUGDacomitinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of dacomitinib might be expected based on their molecular tumor profile.
LorlatinibDRUGLorlatinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of lorlatinib might be expected based on their molecular tumor profile.
ErdafitinibDRUGErdafitinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of erdafitinib might be expected based on their molecular tumor profile.
AlpelisibDRUGAlpelisib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of alpelisib might be expected based on their molecular tumor profile.
NiraparibDRUGNiraparib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of niraparib might be expected based on their molecular tumor profile.
PemigatinibDRUGPemigatinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of pemigatinib might be expected based on their molecular tumor profile.
SelpercatinibDRUGSelpercatinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of selpercatinib might be expected based on their molecular tumor profile.
TepotinibDRUGTepotinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of tepotinib might be expected based on their molecular tumor profile.
fluorouracilDRUGAdministered intravenously. A bolus of 400 mg/m2 to be followed by a continuous infusion over 46 hrs at a dose of 2400mg/m2.
leucovorin calciumDRUGLeucovorin will be administered at a dose of 200 mg/m2 over 120 minutes prior to the 5-FU bolus. Leucovorin may be run simultaneously with irinotecan infusion via y-site connection.
Panitumumab + paclitaxelDRUGPaclitaxel 80 mg/m2 may be infused, intravenously, over one hour every week. Panitumumab will be administered every 2 weeks at a dose of 6 mg/kg, using a non pyrogenic low protein binding filter with a 0.20-0.22-μm pore size intravenously over 1 hour ± 15 minutes. Panitumumab will be administered prior to paclitaxel.
OxaliplatinDRUG85 mg/m2, 2-hour IV infusion every 2 weeks
LeucovorinDRUG200 mg/m2, 2-hour IV infusion every 2 weeks
5-FluorouracilDRUG3200 mg/m2 IV, 48-hour continuous infusion every two weeks
PemetrexedDRUGPemetrexed 500mg/m² IV, Day 1 of Cycles 1-6 (Cycles are 3 weeks / 21 days in length)
mFOLFOX6DRUGmFOLFOX6 regimen is a combination therapy of oxaliplatin (85 mg/m\^2) administered as a 2-hour infusion on Day 1; leucovorin (400 mg/m\^2) administered as a 2-hour infusion on Day 1; followed by a loading dose of 5-fluorouracil (5-FU; 400 mg/m\^2) IV bolus administered over approximately 2 to 4 minutes on Day 1, then 5- FU (2400 mg/m\^2) via ambulatory pump administered for a period of 46 to 48 hours.
cisplatinDRUG -
docetaxelDRUG -
neoadjuvant therapyPROCEDURE -
therapeutic conventional surgeryPROCEDURE -
radiation therapyRADIATION -
5FUDRUGThis is a PK study comparing Panitumumab plus Chemotherapy to Chemotherapy alone
Standard Fractionation RadiotherapyRADIATION70 Gy administered in 2 Gy fractions daily for 5 days a week for 7 weeks (35 fractions)
Pre-emptive Skin TreatmentDRUGPre-emptive skin treatment included a skin moisturizer (eg, Lubriderm), sunscreen (free of paraaminobenzoic acid (PABA), skin protection factor (SPF) 15 or higher, ultraviolet-A (UV-A), and UV-B protection), topical steroid (1% hydrocortisone cream) and oral antibiotic (doxycycline, 100 mg twice daily).
Reactive Skin TreatmentDRUGTreatment was based on symptoms and severity and may have included an emollient (eg, Lubriderm, Vaseline), sunscreen (SPF ≥ 15), oral antibiotic (eg, doxycycline, ciprofloxacin, cefadroxil, amoxicillin/clavulanic acid), topical steroid (hydrocortisone cream), topical antibiotic (clindamycin), oral systemic steroid, topical medical treatment (eg, silver sulfadiazine, Silvadene), topical antihistamine or oral antihistamine (hydroxyzine)
Panitumumab (ABX-EGF)DRUGDose received in previous studies will be rolled over to this study. These regimens include: 2.5 mg/kg weekly; 6.0 mg/kg every 2 weeks; and 9.0 mg/kg every 3 weeks.
ConatumumabDRUGAdministered by intravenous infusion
Motesanib diphosphateDRUGDose-finding with an initial dose of 50 mg once daily and up to 125 mg once daily. 75 mg twice daily was also to be tested.
PaclitaxelDRUGPaclitaxel 200 mg/m\^2 administered by IV infusion over 3 hours.
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Eligibility Criteria
Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites78

Inclusion Criteria: * Diagnosis of metastatic colorectal cancer (CRC) * Wild-type (without mutation in codons 12 and 13) KRAS gene in tumor tissue confirmed by a central laboratory * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 * At least 1 measurable or non-measurable ...

Countries:BrazilCanadaChileChinaCroatiaEstoniaGreeceIndiaLatviaLithuaniaMalaysiaMexicoPhilippinesRomaniaSerbiaSouth KoreaUnited StatesAustraliaBelgiumBulgariaCzechiaFranceHong KongIsraelItalyNetherlandsPeruPolandRussiaSingaporeSlovakiaSouth AfricaSwedenTaiwanUnited KingdomGermanySpainAustriaPuerto Rico
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Recent Changes (Last 90 Days)
LOWMay 26, 2026NCT02925234primaryCompletionDate: changed
LOWMay 24, 2026NCT02925234studyFirstPostDate: changed
LOWMay 24, 2026NCT04034173studyFirstPostDate: changed