Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as regorafenib tablet, Regorafenib (Stivarga, BAY73-4506)
Regorafenib · 39 trials · 28 indications
The PFS is defined as the time from date of treatment assignment (i.e., date of first treatment) to date of first observed disease progression or death due to any cause, if death occurs while the subject is in the study (that is, by the last visit including during the safety follow-up visit date), and before progression is observed.
Overall Survival (OS) was defined as the time from date of randomization (Day 1) to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
Progression-free Survival (PFS) was defined as the time from date of randomization to radiological disease progression or death due to any cause, whichever occurs first. PFS was based on central radiological assessment using modified RECIST (Response Evaluation Criteria in Solid Tumors) v.1.1. Progression is defined as at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study; or unequivocal progression of existing non-target lesions; or appearance of new lesions. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation. Results are based on central evaluation.
Overall survival (OS) was defined as the time (days) from randomization to death due to any cause. Patients alive at the time of analysis were censored at the last date known to be alive. If a patient was lost to follow-up and there was no contact after randomization, this patient was censored at Day 1.
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Death is also considered as progression in the analysis.
To assess the efficacy of this regimen in term of overall objective response rate (complete response rate) at 12 weeks as assessed by the Investigator, per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). The number of participants that reach a complete response (CR) defined as normalization of tumor markers, tumor nodes \<10 mm.
To assess the efficacy of this regimen in term of overall objective response rate (partial response rate) at 12 weeks as assessed by the Investigator, per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). The number of participants that reach a partial response (PR)defined as at least a 30% decrease in the sum of diameters of target lesions.
The objective response rate (ORR) will be defined by RECIST v1.1 criteria as the best disease response observed during the treatment period (assessed to 4 months). ORR rate is defined as the proportion of patients whose tumor regresses or does not progress under treatment.
ORR was defined as the percentage of participants with overall response of complete response (CR) or partial response (PR). CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have decreased in size to have a short axis of \< 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.
Progression free survival will be calculated for all patients from the date of randomization until the date PD or death is first reported.
The trial will measure the toxicities of HFSR in participants receiving both perindopril and regorafenib using the CTCAE v4.03 criteria. The toxicity of HFSR will be expressed based on the number of participants in the study (N=10) who are experiencing HFSR of all grades.
10-month PFS Rate is the proportion of participants ramaing alive and progression free at 10 months. Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (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. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
The response rate is the proportion of participants achieving XX based on RECIST 1.1 criteria defined per protocol section 11.1.4 for target lesions.
the sum of complete responses (CR) + partial responses (PR) + stable disease (SD).
PFS according to the RECIST 1.1 criteria, based on the investigator's assessment.
16-week progression free survival was determined for each subject as a binary variable indicating whether or not the subject is alive and progression free at 16 weeks after treatment start, with progression defined radiographically using RECIST v1.1 or clinically based upon investigator assessment.
OR was defined as the best tumor response (confirmed complete response \[CR\] or partial response \[PR\]) observed by MRI or CT scan assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1. CR and PR were confirmed not earlier than 4 weeks following the initial detection of response. CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). Any pathological lymph nodes (whether target or non target) must have a reduction in short axis to \< 10 mm. PR = At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing nontarget lesions and no appearance of new lesions.
Objective tumor response of a participant was defined as the best tumor response (confirmed Complete Response \[CR, tumor disappears\] or Partial Response \[PR, sum of lesion sizes decreased at least 30% from baseline\]) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) committee.
Tumor response of a participant was defined as the best tumor response (confirmed Complete Response \[CR, tumor disappears\], Partial Response \[PR, sum of lesion sizes decreased at least 30% from baseline\], Stable Disease \[SD, steady state of disease\], or Progressive Disease \[PD, sum of lesion sizes increased at least 20% from smallest sum on study or new lesions\]) observed during trial period assessed according to the RECIST committee.
The dose-finding escalation will be driven by the occurrence of Dose-Limiting Toxicities (DLT), assessed over the first 28-day cycle (cycle 1), and defined as any of the following haematological and non-haematological events that occur during the DLT period (4 weeks after the start of treatment = cycle 1) and are at least possibly related (possibly, probably, or definitely) attributable to VDC/IE + regorafenib: * Any cardiac toxicity grade ≥ 3 * Any grade 3 or 4 (hematological or non-hematological) toxicity leading to delay of start of next course by \> 7 days (i.e: starting \> day 21). * Any dose interruption or reduction due to toxicity which results in administration of less than 80% of the planned dosage of regorafenib or 75% of the planned dosage of chemotherapy. * Any grade 3 or 4 toxicity resulting in discontinuation of the new combination * Any grade 5 toxicity related to study treatment (death)
* Grade 3 diarrhea, nausea, vomiting, and loss of appetite if lasting for ≥ 7 consecutive days; * Grade 3 electrolyte imbalance if lasting for ≥ 7 consecutive days; * Grade 3 dermal toxicity if lasting for ≥ 7 consecutive days; * Grade 3 fatigue for ≥ 7 consecutive days; * Grade 4 T-Bil, AST (GOT) and/or ALT (GPT) elevations,
The incidence of treatment-emergent adverse events and treatment-emergent drug-related adverse events summarized in frequency tables using worst CTCAE v4.03 grade.
The procedure for DLT assessment was as follows: 1. When DLT is observed in 1 out of 3 cases, 3 additional cases are added to the administration level. 2. When DLT is observed in more than 2 of 3 cases, it is judged that the administration level exceeds Maximum Tolerated Dose (MTD). 3. If the number of DLT is 1 case or less in 6 cases, shift to the next level. 4. If MTD is exceeded, shift to the next lower level. At the relevant dose, if only 3 people are evaluating DLT, add 3 cases. When the number of DLT is 1 or less out of 6, the dose is defined as MTD and RD. If it is judged that Level 1 exceeds the MTD, review the dose or consider stopping the trial. 5. MTD should be the highest dose level of DLT expression less than 1 in 6 cases. - After the RD was determined and the patient moved to the expansion cohort, G3 skin toxicity occurred, so based on the recommendation of the Data and Safety Monitoring Committee, the RD was reduced by one level and the trial was resumed.
Dose-escalation cohort is to determine the frequency and characteristics of DLTs of alternation of sunitinib and regorafenib at each dose level during the first cycle of therapy. Toxicity will be graded accordingly with NCI CTCAE version 4.0
MTD is defined as the dose level at which none or 1 of 6 participants experiences dose-limiting toxicity (DLT), when at least 2 of 3-6 participants experience a DLT at the next highest dose
In order to establish a RP2D, the MTD cohort will be expanded to have at least 12 evaluable subjects to confirm the RP2D. It is expected that at least 15 subjects evaluable for DLTs will be necessary to establish the RP2D of the combination"
Individual listings of adverse events will be provided. The incidence of treatment-emergent adverse events and drug-related adverse events, respectively, will be summarized by worst NCI-CTCAE v 4.0 grade and by dose level
Dose escalation phase has been completed
MTD is defined as the maximum dose at which the incidence of dose-limiting toxicities (DLTs) during Cycle 1 is below 20 %, or as the maximum dose administered, whichever is achieved first during dose escalation
Based on non-compartmental PK evaluation. The AUC(0-tlast) \[Area Under the Concentration-time Curve After Single (First) Dose From Time Zero to the Last Data Point \>LLOQ (Lower Limit of Quantification)\] is a measure of systemic drug exposure from time 0 up to the time point at which the last measurable drug could be detectable, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Amount of drug excreted into urine during the collection interval 0-24 hours post dose was expressed as percentage of administered dose.
| Arm | Type | Description |
|---|---|---|
| Regorafenib | EXPERIMENTAL | Regorafenib, 40 mg tablets |
| Placebo | PLACEBO_COMPARATOR | 4 matching placebo tablets for 3 weeks of every 4 week cycle (i.e. 3 weeks on, 1 week off) plus BSC |
| Arm 1 | EXPERIMENTAL | - |
| Arm 2 | PLACEBO_COMPARATOR | - |
| Regorafenib (Stivarga, BAY73-4506) | EXPERIMENTAL | Participants received Regorafenib (Stivarga) 160 mg (4 x 40 mg tablets) per os once daily, 3 weeks on therapy followed by 1 week off therapy to comprise a cycle of 4 weeks |
| Regorafenib (Stivarga, BAY73-4506)+BSC | EXPERIMENTAL | Participants received Regorafenib 160 mg per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus Best Supportive Care(BSC). |
| Placebo+BSC | PLACEBO_COMPARATOR | Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus Best Supportive Care (BSC). |
| Oral Regorafenib combined with intra-muscular injection of Fulvestrant | EXPERIMENTAL | Oral regorafenib in a ReDOS plan (80 mg week#1, 120 mg week#2, 160 mg week#3 for cycle #1 then adjust final dose for subsequent cycles based on tolerance during cycle #1) \[3 weeks on/1 week off\] combined with intramuscular injection of fulvestrant 500 mg day #1 (day #15 will be planned only in cycle #1) in a 28-day cycle till disease progression or unacceptable toxicities |
| Experimental | EXPERIMENTAL | REGORAFENIB: * For the first cycle: regorafenib will be administered according to the "REDOS" schedule (80 mg daily for week 1, 120 mg daily for week 2 and 160 mg daily for the third week of the first cycle). * For the following cycles: regorafenib will be administered at a 80, 120 or 160 mg daily dose according to toxicity observed with the last dose used in the first cycle. METRONOMIC CHEMOTHERAPIES: * Capecitabine: 625mg/m²/orally twice daily continuously for 6 months * Cyclophosphamide: 50 mg per os, daily, for 6 months ASPIRIN: 75 mg orally and daily until progression |
| Regorafenib + Nivolumab | EXPERIMENTAL | - |
| Regorafenib and Perindopril | EXPERIMENTAL | Phase II, open label, single arm trial of patient with refractory mCRC treated with regorafenib (10 mg/day) and perindopril (4 mg/day). There will be no stratification in this study. |
| ARM A - Regorafenib | EXPERIMENTAL | Patients receive REGORAFENIB 40 mg tablets once daily (160 mg/die), 3 weeks on, 1 week off, until disease progression or unacceptable toxicity. |
| ARM B - Lomustine | ACTIVE_COMPARATOR | Patients receive LOMUSTINE 110 mg/m2 orally on day 1, every 6 weeks (q6w), until disease progression or unacceptable toxicity. |
| Unique arm | OTHER | Regorafenib 160mg once a day, frequency: 3 weeks on/1 week off in cycles of 28 days |
| A-Tamoxifen | ACTIVE_COMPARATOR | Tamoxifen 40mg/day 2 film-coated tablet containing 20 mg of Tamoxifen/day until progression |
| B-Regorafenib | EXPERIMENTAL | Regorafenib 120mg/day 3 film-coated tablet containing 40 mg of Regorafenib/day, 3 weeks/4 until progression |
| Regorafenib (BAY73-4506) | EXPERIMENTAL | Regorafenib 160 mg orally once a day for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off). |
| Single Arm | EXPERIMENTAL | Oral Regorafenib |
| Regorafenib + oxaliplatin/folinic acid/5-FU (mFOLFOX6) | EXPERIMENTAL | On Day 1, participants received 85 mg/m\^2 oxaliplatin as a 2-hour intravenous (IV) infusion and folinic acid (either 400 mg/m\^2 D/L-folinic acid or 200 mg/m\^2 L-folinic acid) as a 2-hour IV infusion. Once the initial infusion was completed, participants received 5-FU 400 mg/m\^2 IV bolus injection immediately followed by a 5-FU 2400 mg/m\^2 IV infusion for 46 hours. The next cycle of mFOLFOX6 was administered on Day 15 to 17. Participants received Regorafenib (Stivarga, BAY73-4506) 160 mg orally (po) once daily (qd) on Days 4 to 10 and Days 18 to 24. One cycle comprised 28 days. |
| Induction chemotherapy (VDC/IE) and local treatment /consolidation chemotherapy | EXPERIMENTAL | Standard ES treatment consists of: induction chemotherapy (VDC/IE) and local treatment (surgery/radiotherapy), followed by consolidation chemotherapy (VC/IE)/ Bu-Mel (according to physician and patient choice). Regorafenib will be administered during induction chemotherapy (VDC/IE) and during consolidation chemotherapy with conventional chemotherapy (VC/IE) but not Bu-Mel therapy Conventional chemotherapy will be administered at the recommended dose (100%) and only regorafenib will be escalated/de-escalated. Regorafenib will only be given concomitant to radiotherapy in case the primary tumor is located in the extremities. In case of primary tumors located in the pelvis, abdomen, thorax, spine, brain, head or neck, regorafenib will be stopped at least 1 week before start of radiotherapy. |
| Cohort A (Adjuvant/Maintenance Phase) | EXPERIMENTAL | - |
| Cohort B (Concomitant Phase) | EXPERIMENTAL | - |
| Dose escalation | EXPERIMENTAL | The regorafenib starting dose will be 120 mg q.d.(once daily) 3 weeks on / 1 week off in combination with the recommended dose of pembrolizumab (200 mg Q3W). Pembrolizumab dose will not be escalated or de-escalated. |
| Dose expansion | EXPERIMENTAL | Dose expansion cohorts will continue to be expanded until the sample size of 30-35 patients per cohort is reached. |
| Level 1 | ACTIVE_COMPARATOR | Regorafenib: Oral administration at a dose of 80 mg given once per day for 21 consecutive days, with a 1-week washout period. Nivolumab: Given once every 2 weeks at a dose of 3.0 mg/kg via an intravenous infusion. When it is deemed that there is no problem with safety at the doses described above, tolerability will be verified at the level-2 dosages described below. |
| Level 2 | ACTIVE_COMPARATOR | Regorafenib: Oral administration at a dose of 120 mg/day for 21 consecutive days, with a 1-week washout period. Nivolumab: Given once every 2 weeks at a dose of 3.0 mg/kg. When it is deemed that there is no problem with safety at the doses described above, tolerability will be verified at the level-3 dosages described below. |
| Level 3 | ACTIVE_COMPARATOR | Regorafenib: Oral administration at a dose of 160 mg/day for 21 consecutive days, with a 1-week washout period. Nivolumab: Given once every 2 weeks at a dose of 3.0 mg/kg. After starting the trial, three cases are registered at level 1, and temporary case registration is suspended until safety evaluation of the first course is completed in all cases. If there are cases in which evaluation of DLT can not be performed properly, such as being canceled due to reasons other than safety during the course of the first course, the necessary number of cases is appropriately added to the administration level. |
| Expansion cohort | ACTIVE_COMPARATOR | After completion of the final DLT evaluation period of the subjects in the dose escalating cohort, the decision to move the subjects into the expansion cohort will be determined once it is decided, upon deliberation between the sponsor and the principal investigator, that there are no problems associated with moving on. Furthermore, the opinion of the Data and Safety Monitoring Committee (DSMC) can be sought as required . Regarding the review of RD in the expansion cohort, please refer to "Analysis Population Description" in Primary Outcome Measures. |
| Sunitinib alternated with Regorafenib | EXPERIMENTAL | The treatment cycle is defined as 28 days. Treatment consists of 3 days of once daily sunitinib alternating with 4 days of once daily regorafenib throughout each cycle. The starting dose level is sunitinib 37.5 mg/d and regorafenib 120 mg/d, and doses will be escalated in subsequent cohorts following a classical 3+3 design up to sunitinib 50 mg/d and regorafenib 160 mg/d or until maximum tolerable dosage and recommended phase II dose is determined. An alternative scheme of 4-week cycles of the same regimen but with 21 days of dosing followed by 7 days of rest will be studied in case of toxicities during d 22-28 of the starting 4-weeks continuous cycles. Tumor assessments performed at baseline and after every two dosing cycles to assess response. Toxicity monitored throughout the study. |
| P-gp probe substrate(digoxin)+regorafenib | EXPERIMENTAL | - |
| Group B: BCRP probe substrate (rosuvastatin) + regorafenib | EXPERIMENTAL | - |
| Sequential dosing schedule | EXPERIMENTAL | Expansion phase: Schedule B - Sequential dosing schedule: Of a 21-day cycle, regorafenib will be dosed sequentially, following administration of VI: Vincristine：intravenous bolus, 1.5 mg/m2 (0.05 mg/kg for subjects ≤ 10 kg), Day 1 and Day 8. Irinotecan: intravenously over 1 hour, 50mg/m2/day, Day 1 to Day 5. Regorafenib: orally, at a starting dose level of 72 mg/m2 (subjects 2 to less than 18 years old) or 60 mg/m2 (subjects 6 to less than 24 months old) once daily, Day 8 to Day 21. |
| Concomitant dosing schedule | EXPERIMENTAL | Expansion phase: Schedule A - Concomitant dosing schedule: Of a 21-day cycle, regorafenib will be concomitantly administered with vincristine and irinotecan (VI): Vincristine: intravenous bolus, 1.5 mg/m2 (0.05 mg/kg for subjects ≤ 10 kg), Day 1 and Day 8. Irinotecan: intravenously over 1 hour, 50 mg/m2/day, Day 1 to Day 5. Regorafenib: orally, at a starting dose level of 72 mg/m2 (subjects 2 to less than 18 years old) or 60 mg/m2 (subjects 6 to less than 24 months old) once daily, Day 1 to Day 14. |
| Neomycin | EXPERIMENTAL | - |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | EXPERIMENTAL | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Regorafenib (Stivarga, BAY73-4506)-Severe Renal Impairment | EXPERIMENTAL | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Arm 3 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Regorafenib (Stivarga, BAY73- 4506) | DRUG | 160 mg regorafenib per oral every day for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off) |
| Regorafenib (Stivarga, BAY73-4506) | DRUG | Regorafenib, 40 mg tablets |
| Placebo | DRUG | Placebo tablets matching in appearance |
| Regorafenib (BAY73-4506) | DRUG | Regorafenib BAY73-4506 will be given 3 weeks on/1 week off (160 mg od po.) |
| Best supportive care | DRUG | Best supportive care includes any method to preserve the comfort and dignity of the patients, and excludes any disease-specific anti-neoplastic therapy such as any kinase inhibitor, chemotherapy, radiation therapy, or surgical intervention. |
| Best Supportive Care (BSC) | OTHER | BSC includes any concomitant medications or treatments: antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any other symptomatic therapy necessary to provide BSC, except other investigational anti-tumor agents or anti-neoplastic chemo/hormonal/immuno-therapy. |
| Regorafenib | DRUG | Regorafenib will be packaged as 40 mg tablets in a bottle. Patients will be instructed to maintain a daily medication calendar. |
| Fulvestrant | DRUG | 500 mg day #1 (day #15 will be planned only in cycle #1) in a 28-day cycle till disease progression or unacceptable toxicities |
| Cyclophosphamide | DRUG | 50 mg per os, daily, for 6 months |
| Capecitabine | DRUG | 625mg/m²/orally twice daily continuously for 6 months |
| Aspirin | DRUG | 75 mg orally and daily until progression |
| Nivolumab (Opdivo) | BIOLOGICAL | Administered on day 1 of every treatment cycle. |
| Perindopril | DRUG | COVERSYL® (perindopril erbumine) 4 mg will be administered daily for 21 days of a 28 day cycle. Perindopril will be administered orally, first thing in the morning on an empty stomach. |
| Lomustine | DRUG | Lomustine is formulated as tablets of 40mg for oral administration. |
| Tamoxifen | DRUG | Tamoxifen: 40 mg/day |
| Oxaliplatin | DRUG | On day 1 and day 15 of each cycle, participants will receive 85 mg/m\^2 oxaliplatin as a 2 hour i.v. infusion. |
| Folinic acid | DRUG | On day 1 and day 15 of each cycle, participants will receive folinic acid (either 400 mg/m\^2 D/L-folinic acid or 200 mg/m\^2 L-folinic acid) as a 2 hour i.v. infusion. |
| 5-FU (mFOLFOX6) | DRUG | Participants will receive a 400 mg/m\^2 5 FU i.v. bolus injection immediately followed by a 2400 mg/m\^2 5 FU 46 hour i.v. infusion. |
| regorafenib tablet | DRUG | Regorafenib will be escalated/de-escalated, starting at DL0: * DL1: 82 mg/m\^2 once daily for 21 days/28 days (max 160mg) (100% of the RP2D) * DL0 (starting dose): 66 mg/m\^2 once daily for 21 days/28 days (max 120mg) (80% of the RP2D) * DL-1: 50 mg/m\^2 once daily for 21 days/28 days (max 80mg) (60% of the RP2D) |
| Temozolomide | DRUG | Following a "3+3" design, in cohort A three patients will be administered temozolomide 150-200 mg/m2 for 5 consecutive days every 28 days until 6-12 cycles and regorafenib daily for 21 days, with a 1-week washout period at dose of 80 mg (level 1), 120 mg (level 2), or 160 mg (level 3) (regorafenib 40 mg- level -1). As a general rule, one cycle will last 28 days (day 1-28); however, in the event of treatment prolongation, the cycle period will be extended. In cohort B,During concomitant therapy phase: temozolomide 75 mg/m2/die for 42 (max 49 days) consecutive days (concomitant with radiation therapy). |
| Regorafenib(Stivarga, BAY73-4506) | DRUG | Regorafenib 80mg/120mg/160mg q.d., 3 weeks on / 1 week off + pembrolizumab 200mg i.v. every 3 weeks |
| Pembrolizumab | DRUG | 200 mg i.v.(Intravenous(ly)) every 3 weeks (Q3W). This dose will not be escalated or deescalated and the dosing schedule will not be changed |
| Nivolumab | DRUG | One course will last 28 days. Given once every 2 weeks at a dose of 3.0 mg/kg. |
| Sunitinib | DRUG | Intervention Description: 3 days of once daily sunitinib alternating with 4 days of once daily regorafenib throughout each 28 day cycle. The starting dose level (level 1) is sunitinib 37.5 mg/d and regorafenib 120 mg/d, and doses will be escalated in subsequent cohorts following a classical 3+3 design up to sunitinib 50 mg/d and regorafenib 160 mg/d or until maximum tolerable dosage (MTD) and recommended phase II dose (RP2D) is determined. Number of Cycles: until progression or unacceptable toxicity develops. |
| Digoxin | DRUG | Single dose of digoxin 0.5 mg (2 tablets 0.25 mg) orally without and with regorafenib |
| Rosuvastatin | DRUG | Single dose of rosuvastatin 5mg (1 tablet 5 mg) without and with regorafenib 160 mg q.d. (4 tablets 40 mg) |
| Vincristine (Cellcristin®) | DRUG | Vincristine will be given at a dose of 1.5 mg/m2 (0.05 mg/kg for subjects ≤ 10 kg, maximum 2.0 mg) on Day 1 and Day 8 in 21-day cycles. |
| Irinotecan (Irinotecan Cell pharm®) | DRUG | Irinotecan will be administered at a starting dose of 50 mg/m2/day from Day 1 to Day 5, in 21 day cycles. |
| Neomycin | DRUG | 1 g tid (three times a day) regimen of Neomycin (oral) on five days in Period 2 starting 4 days before regorafenib intake on day 1 in period 2. |
| Cetuximab (ERBITUX) | DRUG | - |
| Warfarin | DRUG | CYP 2C9 (warfarin) at Cycle 1 |
| Omeprazole | DRUG | CYP 2C19 (omeprazole) at Cycle 1 |
| Midazolam | DRUG | CYP 3A4 (midazolam) at Cycle 1 |
| Rosiglitazone | DRUG | CYP2C8 (rosiglitazone) at Cycle 1 |
| Regorafenib (BAY73-4506) + rifampin | DRUG | Drug: BAY73-4506 A single 160-mg dose of BAY73-4506 will be administered in the fasted state on Day 1 as four 40 mg tablets. Drug: BAY73-4506 and rifampin 600 mg once a day doses of rifampin will be orally administered after overnight fasting from Day 15 to Day 23. A single 160-mg dose of BAY73-4506 will be administered in the fasted state on Day 21 as four 40 mg tablets. |
Inclusion Criteria: * Male or female subjects \>/= 18 years of age * Life expectancy of at least 3 months * Histological or cytological documentation of adenocarcinoma of the colon or rectum * Subjects with metastatic colorectal cancer (Stage IV) * Progression during or within 3 months following th...
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Regorafenib is an investigational small molecule being studied for use in oncology, including glioblastoma multiforme, solid malignant tumors, tumors, gastrointestinal stromal tumor, gastric cancer, and metastatic colorectal cancer. It is currently in Phase 1 clinical development and is not yet approved by the FDA.
Regorafenib is a kinase inhibitor that targets multiple proteins, including DDR2, EPHA2, FGFR2, MAPK11, PDGFRB, PDGFRA, BRAF, KIT, TEK, FGFR1, NTRK1, RAF1, ABL1, FRK, RET, FLT1, FLT4, and KDR. It works by inhibiting these molecular targets, which are involved in tumor growth and progression.
Regorafenib is being developed by Bayer AG, a company traded under the ticker BAYRY. The drug is also known as regorafenib tablet, Stivarga, and BAY73-4506.
Regorafenib is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. Clinical trials are ongoing to evaluate its safety and efficacy in various oncology indications.
Regorafenib has been studied in several clinical trials, including NCT00664326, a Phase 2 study in renal cell carcinoma; NCT00960258, a Phase 1 study in Japanese patients with solid tumors; NCT02584465, a Phase 2 study in ovarian carcinoma; and NCT03406871, a Phase 1 study combining regorafenib with nivolumab in advanced solid tumors.
Yes, Regorafenib is also known as Stivarga and BAY73-4506. It is marketed under the brand name Stivarga and is being developed by Bayer AG for multiple oncology indications.