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CP-751, 871+ carboplatin+ paclitaxel

Phase 2

Colorectal Neoplasm | Monoclonal antibody | Oncology |Pfizer, Inc.|Last Updated: Oct 28, 2015

Target and mechanism

ModalityMonoclonal antibody

Also known as CP-751,871, CP-751, 871

Success Probability

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Market & Valuation

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Trial Design

UNCONTROLLED
Total Trials1
Total Enrollment168

FDA Designations

No designations recorded

Clinical trial landscape

CP-751, 871+ carboplatin+ paclitaxel · 9 trials · 7 indications

Phase 2 2Phase 1 7
NCT00560560Study Using CP-751,871 In Patients With Stage IV Colorectal Cancer That Has Not Responded To Previous Anti-Cancer TreatmentsColorectal Neoplasm
COMPLETED168 Analytics
NCT00313781Study of CP-751,871 in Combination With Docetaxel and Prednisone in Patients With Hormone Insensitive Prostate Cancer (HRPC)Prostatic Neoplasms
COMPLETED204 Analytics
PHASE2COMPLETED
Study Using CP-751,871 In Patients With Stage IV Colorectal Cancer That Has Not Responded To Previous Anti-Cancer Treatments
Colorectal NeoplasmUnlock trial analytics
PHASE2COMPLETED
Study of CP-751,871 in Combination With Docetaxel and Prednisone in Patients With Hormone Insensitive Prostate Cancer (HRPC)
Prostatic NeoplasmsUnlock trial analytics

Study Endpoints

Primary Endpoints

Estimate of the 6 Month Survival Probability
Baseline up to Month 6

The 6 month survival probability was defined as the probability of survival at 6 months based on the Kaplan-Meier estimate. The time was from date of enrollment to date of death due to any cause. For participants who were last known to be alive, overall survival was censored at the last contact date.

Percentage of Participants With Prostate Specific Antigen (PSA) Best Response
Baseline, Day 1 and Day 15 of each cycle, end of treatment (up to 28 days post last dose) and follow-up (monthly, up to 150 days post last dose)

Percentage of participants with PSA best response of either PSA normalization (PN) or partial PSA response (PR) relative to the total number of participants evaluable for response. PN was defined as PSA =\< 0.2 nanogram/milliliter (ng/ml) on 2 successive evaluations at least 3 weeks apart and no imaging or clinical evidence of disease progression. PP was defined as \>= 50% decrease in PSA from baseline on 2 successive evaluations at least 3 weeks apart and no imaging or clinical evidence of disease progression.

Objective Response Rate (ORR)
Baseline and every cycle (4 weeks), for up to 6 cycles

Percentage of participants with objective response based on assessment of confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as complete disappearance of all target and non-target disease and no new lesions. PR was defined as ≥30% decrease under baseline of the sum of diameters of all target lesions.

Number of Participants With Dose Limiting Toxicities (DLT)
Cycle 1

A DLT was defined as any one of the following adverse events observed in Cycle 1 which was considered as related to CP-751,871 combination therapy; 1) \>=Grade 3 gastrointestinal toxicity, hyperglycemia and/or fatigue despite the use of adequate/optimal medical intervention, 2) Any other \>=Grade 3 toxicity not classified under CTCAE blood/bone marrow, or 3) Grade 4 neutropenia that persisted for \>=7 consecutive days or was complicated by fever (defined as a body temperature \>38.0 Celsius degree), 4) Grade 3 thrombocytopenia which needed blood transfusion or Grade 4 thrombocytopenia.

Number of Participants With Dose-limiting Toxicities (DLT)
Start of treatment up to end of Cycle 1, Day 21

Cycle 1 figitumumab attributed: Grade (Gr) 4 neutropenia (absolute neutrophil count \<500 cells/cubic millimeter \[mm\^3\]) \>=7 days, febrile neutropenia (Gr 3, fever \>=38.5 degrees Celsius), neutropenic infection (Gr 3 neutropenia, infection); Gr 4 thrombocytopenia (platelet \<25,000 cells/mm\^3), Gr 3 thrombocytopenia \>=7 days/bleeding; other Gr 3 not blood/bone marrow Common Terminology Criteria for Adverse Events bar gastrointestinal toxicity, treatment-managed hyperglycemia/fatigue, hypersensitivity; Gr 3-4 hyperglycemia despite treatment; fail to adequately recover to continue study treatment

Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Baseline up to 150 days after the last administration of study drug

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 150 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Maximum Tolerated Dose (MTD)
Cycle 1 Day 1 through Cycle 1 Day 21
Recommended Phase 2 Dose (RP2D)
Cycle 1 Day 1 through Cycle 1 Day 21
Area Under the Curve From Time Zero to 25 Hours Postdose (AUC25) of Docetaxel in Cycle 1
30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion

Area under the plasma concentration versus time curve (AUC) from time zero to 25 hours post dose, the nominal time of the last sample (24 hours after end of infusion)

Area Under the Curve From Time Zero to 25 Hours Postdose (AUC25) of Docetaxel in Cycle 4
30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion

Area under the plasma concentration versus time curve (AUC) from time zero to 25 hours post dose, the nominal time of the last sample (24 hours after end of infusion)

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Docetaxel in Cycle 1
30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Docetaxel in Cycle 4
30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn)) of Docetaxel in Cycle 1
30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) divided by dose

Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn)) of Docetaxel in Cycle 4
30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) divided by dose

Maximum Observed Plasma Concentration (Cmax) of Docetaxel in Cycle 1
30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Maximum Observed Plasma Concentration (Cmax) of Docetaxel in Cycle 4
30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Dose Normalized Maximum Observed Plasma Concentration (Cmax(dn)) of Docetaxel in Cycle 1
30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion

Maximum Observed Plasma Concentration (Cmax) divided by dose

Dose Normalized Maximum Observed Plasma Concentration (Cmax(dn)) of Docetaxel in Cycle 4
30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion

Maximum Observed Plasma Concentration (Cmax) divided by dose

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Docetaxel in Cycle 1
30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Docetaxel in Cycle 4
30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
Maximum Tolerated Dose (MTD)of CP-751,871 in Combination With Paclitaxel and Carboplatin: Phase 1b
Start of treatment (baseline) up to the end of Cycle 1 (Day 21)

The maximum tolerated dose of CP-751,871 in combination with paclitaxel and carboplatin is the highest dose level below the Maximum Administered Dose (the dose level at which 2 or more out of 3 to 6 patients experience a Dose Limiting Toxicity at a dose level in Cycle 1) at which none or one out of 6 patients experience a Cycle 1 Dose Limiting Toxicity.

Recommended Phase 2 Dose (RP2D): Phase 1b
Start of treatment (baseline) up to the end of Cycle 1 (Day 21)
Objective Response Rate: Phase 2
Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization

Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.

Objective Response Rate in Non-Adenocarcinoma Participants: Phase 2
Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization

Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.

Secondary Endpoints

Overall Survival
From date of enrollment until death or censorship, up to 33 months
Progression-Free Survival (PFS)
Baseline until tumor progression or censorship, up to 33 months. The frequency of tumor assessments was screening, every cycle, end of treatment (within 28 days of last dose of study drug), and follow-up.
Percentage of Participants With Objective Response
Baseline, every cycle (Day 15-21 or according to local standard), end of treatment (within 28 days of last dose of study drug) and follow-up (150 days after last dose of study drug), up to 33 months
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
1EXPERIMENTALSingle arm study
AEXPERIMENTALFor patients treated with docetaxel and prednisone only, who progress during treatment, CP-751,871 will be added to the regimen to test reversibility of chemoresistance.
BACTIVE_COMPARATOR -
CP-751,871EXPERIMENTAL -
CP-751,871 combined with docetaxelEXPERIMENTAL -
Phase 2 (Arms A & B)EXPERIMENTALCP-751,871 + paclitaxel + carboplatin
Phase 1bEXPERIMENTAL1. Phase 1b Dose Escalation /Expansion: CP-751,871 + paclitaxel + carboplatin 2. Phase 1b Erlotinib Extension: CP-751,871 + paclitaxel + carboplatin + erlotinib
Single agent CP-751,871EXPERIMENTALdose escalation design

Interventions

NameTypeDescription
CP-751, 871BIOLOGICALHuman IgG2 Monoclonal Antibody. 20mg/kg or 30 mg/kg every 3 weeks for 17 cycles, until progression or unacceptable toxicity develops.
CP-751,871DRUGCP-750,871 is administered intravenously at a dose of 20 mg/kg on day 1 of each 21-day cycle (for patient convenience and logistical management, the dose of CP-751,871 may be deferred up to 7 days).
docetaxelDRUGDocetaxel is administered IV on day 1 of each 21-day cycle, at a dose of 75 mg/m2.
prednisoneDRUGPrednisone is administered at a dose of 5 mg twice daily.
CP-751,871 + carboplatin + paclitaxelDRUGChemotherapy (carboplatin and paclitaxel) and CP-751,871 (6, 10 or 20mg/kg) will be administered by intravenous infusion every three weeks.
CisplatinDRUGCisplatin 75\* mg/m2 or 80\* mg/m2, IV on Day 1 of each 21-day cycle up to 6 cycles. \* 75 mg/m2 when in combination with pemetrexed, 80 mg/m2 when in combination with gemcitabine
GemcitabineDRUGGemcitabine 1250 mg/m2, IV on Days 1 and 8 of each 21-day cycle up to 6 cycles
PemetrexedDRUGPemetrexed 500 mg/m2, IV on Day 1 of each 21-day cycle up to 6 cycle
paclitaxelDRUGPhase 2 Arm A: Paclitaxel 200 mg/m2, IV over 3 hours up to 6 cycles Phase 2 Arm B: Paclitaxel 200 mg/m2, IV over 3 hours up to 6 cycles
carboplatinDRUGPhase 2 Arm A: Carboplatin AUC 6, IV over 15-60 minutes up to 6 cycles Phase 2 Arm B: Carboplatin AUC 6, IV over 15-60 minutes up to 6 cycles
erlotinibDRUGPhase 1b Erlotinib Extension: erlotinib 150 mg/day orally every day (up to 17 cycles)
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites12

Inclusion Criteria: * Patients who have stage IV colorectal cancer * Patients whose disease has worsened despite prior anti-cancer therapy * Patients who have satisfactory bonemarrow, kidney and liver function Exclusion Criteria: * Patients who are being simultaneously treated with another anti-c...

Countries:United StatesSpainUnited KingdomCanadaGermanySwitzerlandAustraliaBrazilChileFranceIsraelItalyJapanBelgiumIreland
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Frequently asked questions about CP-751, 871+ carboplatin+ paclitaxel

What is CP-751,871 used for?

CP-751,871 is an investigational small molecule studied in combination with carboplatin and paclitaxel for advanced non-small cell lung cancer. It has also been evaluated in advanced non-hematologic malignancies, multiple myeloma, colorectal neoplasm, Ewing's sarcoma family of tumors, and prostatic neoplasms. It is not an approved therapy and remains in clinical development.

Who is developing CP-751,871?

Pfizer, Inc. is the developer of CP-751,871. Pfizer trades on the New York Stock Exchange under the ticker PFE. The company has sponsored Phase 1 studies of the agent in advanced solid tumors and hematologic cancers, including lung cancer and multiple myeloma.

What phase is CP-751,871 in?

CP-751,871 is in Phase 1 clinical development. Three Phase 1 trials have been completed, with no active trials ongoing. The studies together enrolled 347 participants. The program has not advanced beyond early-stage testing, and the drug is investigational rather than approved.

What clinical trials has CP-751,871 been studied in?

CP-751,871 has been studied in three completed Phase 1 trials. NCT00603538 tested it with carboplatin and paclitaxel in advanced lung cancer in Japan. NCT00560573 combined it with cisplatin and gemcitabine in chemotherapy-naive advanced non-small cell lung cancer. NCT01536145 evaluated it in multiple myeloma, and NCT01653158 studied it with docetaxel in advanced non-hematologic malignancies.

Is CP-751,871 the same as CP-751, 871?

Yes. CP-751,871, CP-751, 871, and CP-751,871 plus carboplatin plus paclitaxel all refer to the same Pfizer compound and its combination regimen. The variations are formatting differences in how the agent and its chemotherapy partners are written in study records and publications.

How was CP-751,871 administered in its lung cancer studies?

In the lung cancer trials, CP-751,871 was given in combination with platinum-based chemotherapy. NCT00603538 paired it with carboplatin and paclitaxel in Japanese patients with advanced non-small cell lung cancer, while NCT00560573 paired it with cisplatin and gemcitabine in chemotherapy-naive patients with advanced non-small cell lung cancer.