Safety of AMG 706 Plus Panitumumab Plus Chemotherapy in the Treatment of Subjects With Metastatic Colorectal Cancer
Phase 1
Completed
- Conditions
- Rectal CancerColon Cancer
- Interventions
- Registration Number
- NCT00101894
- Lead Sponsor
- Amgen
- Brief Summary
The purpose of this study is to characterize the safety and tolerability of AMG 706 plus panitumumab when administered with either FOLFIRI or FOLFOX4 chemotherapy regimens. This is a Phase 1b clinical study.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 119
Inclusion Criteria
Not provided
Exclusion Criteria
- More than 1 prior chemotherapy regimen for metastatic CRC
- Central nervous system (CNS) metastases
- History of venous thrombosis
- Myocardial infarction, cerebrovascular accident, transient ischemic attack, grade 2 or greater peripheral vascular disease, congestive heart failure, ongoing arrhythmias requiring medication, or unstable angina within 1 year before study enrollment
- History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on screening chest computed tomograph (CT) scan
- Average systolic blood pressure > 150mm Hg or average diastolic blood pressure of > 90mm Hg
- Radiotherapy within 28 days of study enrollment or within 14 days of study enrollment for peripheral lesions
- Prior AMG 706, oral inhibitors of AMG706, panitumumab, or another anti-EGFr monoclonal antibody (mAb) (e.g., cetuximab [Erbitux®] or EMD 72000)
- Systemic chemotherapy within 28 days before study enrollment
- Major surgery within 28 days or minor surgery within 7days of study enrollment
- History of life threatening ventricular arrhythmia (eg, sustained ventricular tachycardia)
- Female and male subjects of childbearing potential not using adequate contraceptive precautions
- Participation in therapeutic clinical trials within 30 days before study enrollment
- Not recovered from all previous therapies
- Clinically significant open would, ulcer or fracture
- Any co-morbid medical condition that would increase the risk of toxicity
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 2 AMG 706 (MTD) + FOLFOX-4 AMG 706 Maximum Tolerated Dose of AMG 706 established in Part 1b + FOLFOX-4 125 mg QD AMG 706 + FOLFOX-4 FOLFOX-4 125 mg QD AMG 706 + FOLFOX-4 Part 2 AMG 706 (MTD) + FOLFOX-4 FOLFOX-4 Maximum Tolerated Dose of AMG 706 established in Part 1b + FOLFOX-4 125 mg QD AMG 706 + FOLFOX-4 AMG 706 125 mg QD AMG 706 + FOLFOX-4 50 mg QD AMG706 + panitumumab + FOLFIRI Panitumumab (Part 1a only) 50 mg QD AMG706 + panitumumab + FOLFIRI 50 mg QD AMG706 + panitumumab + FOLFIRI FOLFIRI 50 mg QD AMG706 + panitumumab + FOLFIRI Part 2 AMG 706 (MTD) + FOLFIRI FOLFIRI Maximum Tolerated Dose of AMG 706 established in Part 1b + FOLFIRI 100 mg QD AMG 706 + FOLFIRI AMG 706 100 mg AMG 706 + FOLFIRI 100 mg QD AMG 706 + FOLFIRI FOLFIRI 100 mg AMG 706 + FOLFIRI 75 mg QD AMG 706 + panitumumab + FOLFOX-4 FOLFOX-4 75 mg QD AMG 706 + panitumumab + FOLFOX-4 75 mg QD AMG 706 + panitumumab + FOLFOX-4 AMG 706 75 mg QD AMG 706 + panitumumab + FOLFOX-4 75 mg QD AMG 706 + panitumumab + FOLFOX-4 Panitumumab (Part 1a only) 75 mg QD AMG 706 + panitumumab + FOLFOX-4 75 mg BID AMG 706 + panitumumab + FOLFIRI AMG 706 75 mg BID AMG 706 + panitumumab + FOLFIRI 75 mg BID AMG 706 + panitumumab + FOLFIRI Panitumumab (Part 1a only) 75 mg BID AMG 706 + panitumumab + FOLFIRI 75 mg BID AMG 706 + panitumumab + FOLFIRI FOLFIRI 75 mg BID AMG 706 + panitumumab + FOLFIRI 125 mg QD AMG 706 + panitumumab + FOLFIRI AMG 706 125 mg QD AMG 706 + panitumumab + FOLFIRI 125 mg QD AMG 706 + panitumumab + FOLFIRI Panitumumab (Part 1a only) 125 mg QD AMG 706 + panitumumab + FOLFIRI 125 mg QD AMG 706 + panitumumab + FOLFIRI FOLFIRI 125 mg QD AMG 706 + panitumumab + FOLFIRI 125 mg QD AMG 706 + FOLFIRI AMG 706 125 mg QD AMG 706 + FOLFIRI 125 mg QD AMG 706 + FOLFIRI FOLFIRI 125 mg QD AMG 706 + FOLFIRI 100 mg QD AMG 706 + panitumumab + FOLFIRI FOLFIRI 100 mg QD AMG 706 + panitumumab + FOLFIRI 100 mg QD AMG 706 + panitumumab + FOLFIRI AMG 706 100 mg QD AMG 706 + panitumumab + FOLFIRI 100 mg QD AMG 706 + panitumumab + FOLFIRI Panitumumab (Part 1a only) 100 mg QD AMG 706 + panitumumab + FOLFIRI 75 mg QD AMG 706 + FOLFOX-4 FOLFOX-4 75 mg QD AMG 706 + FOLFOX-4 75 mg QD AMG 706 + FOLFOX-4 AMG 706 75 mg QD AMG 706 + FOLFOX-4 100 mg QD AMG 706 + FOLFOX-4 FOLFOX-4 100 mg QD AMG 706 + FOLFOX-4 100 mg QD AMG 706 + FOLFOX-4 AMG 706 100 mg QD AMG 706 + FOLFOX-4 50 mg QD AMG 706 + panitumumab + FOLFOX-4 FOLFOX-4 50 mg QD AMG 706 + panitumumab + FOLFOX-4 50 mg QD AMG 706 + panitumumab + FOLFOX-4 Panitumumab (Part 1a only) 50 mg QD AMG 706 + panitumumab + FOLFOX-4 75 mg QD AMG706 + panitumumab + FOLFIRI AMG 706 75 mg QD AMG706 + panitumumab + FOLFIRI 75 mg QD AMG706 + panitumumab + FOLFIRI Panitumumab (Part 1a only) 75 mg QD AMG706 + panitumumab + FOLFIRI 75 mg QD AMG706 + panitumumab + FOLFIRI FOLFIRI 75 mg QD AMG706 + panitumumab + FOLFIRI 50 mg QD AMG706 + panitumumab + FOLFIRI AMG 706 50 mg QD AMG706 + panitumumab + FOLFIRI Part 2 AMG 706 (MTD) + FOLFIRI AMG 706 Maximum Tolerated Dose of AMG 706 established in Part 1b + FOLFIRI 50 mg QD AMG 706 + panitumumab + FOLFOX-4 AMG 706 50 mg QD AMG 706 + panitumumab + FOLFOX-4
- Primary Outcome Measures
Name Time Method Part 1a - The incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities First 2 cycles Part 1b - The incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities First 2 cycles Part 2 - The overall objective tumor response rate (complete and partial response) in subjects treated with AMG 706 (at the dose determined in Part 1b), with either the FOLFIRI or FOLFOX-4 chemotherapy regimen Every 8 weeks (+/- 7 days)
- Secondary Outcome Measures
Name Time Method Part 1a - The PK of irinotecan (and its active metabolite SN38) when administered as a part of the FOLFIRI regimen with panitumumab and AMG 706 Cycle 1 and 2 (Days 1, 2, 3) Part 1a - The PK of oxaliplatin when administered as a part of the FOLFOX-4 regimen with panitumumab and AMG 706 Cycle 1 and 2 (Day 1) Part 1a - The objective tumor response rate (complete and partial response) throughout the study Every 6 to 8 weeks Part 1b - The incidence of adverse events and clinical laboratory abnormalities not defined as dose-limiting toxicities Every visit Part 1b - The PK of AMG 706 when administered with either the FOLFIRI or FOLFOX-4 chemotherapy regimen Cycle 2 (Day 1-2), Cycle 3 (Day 1) Part 1b - The PK of 5-FU when administered as a part of the FOLFIRI or FOLFOX-4 regimen with AMG 706 Cycle 1 and 2 (Day 3) Part 2 - Duration of response: (Calculated for only those subjects who respond) Time from first objective tumor response (subsequently confirmed at least 4 weeks later) to objective disease progression or death. Part 2 - Time-to-progression Time from first dose of investigational product to objective disease progression or death due to disease progression. Part 1b - The PK of irinotecan (and its active metabolite SN38) when administered as a part of the FOLFIRI regimen with AMG 706 Cycle 1 and 2 (Days 1, 2, 3) Part 1b- The PK of oxaliplatin when administered as a part of the FOLFOX-4 regimen with AMG 706 Cycle 1 and 2 (Day 1) Part 1b - The objective tumor response rate (complete and partial response) throughout the study Every 8 weeks (+/- 7 days) Part 2 - Overall survival Time from first dose of investigational product to death. Subjects who have not died while on study or are lost to follow-up will be censored at their last contact date. (Time on study plus 36 months of long term follow-up) Part 2 - The incidence of adverse events and clinical laboratory abnormalities Every visit Part 2 - The PK of AMG 706 when administered with either the FOLFIRI or FOLFOX-4 chemotherapy regimen (at a subset of the study centers with the capabilities to draw, ship and process PK samples) Cycles 2, 4, 7, and every 3 subsequent cycles (Day 1) Exploratory - Potential biomarker development based on assessment of blood cells, tumor cells, and urine and the proposed mechanism of action of study drugs, and response Day 1 of cycles 1 and 2, and within 7 days of a radiographic assessment Exploratory - The effects of genetic variation in drug metabolism genes, cancer genes, and drug target genes on subject response to investigational products (separate informed consent) Day 1 of cycles 1 and 2, and within 7 days of a radiographic assessment Part 2 - Progression-free survival time Time from first dose of investigational product to objective disease progression or death, subjects who have not progressed or died while on study will be censored at their last evaluable assessment date. Part 2 - Incidence of subjects undergoing resection of metastases for curative intent As needed Part 1a - The incidence of adverse events and clinical laboratory abnormalities not defined as dose-limiting toxicities Every visit Part 1a - The PK of AMG 706 when administered with panitumumab and either the FOLFIRI or FOLFOX-4 chemotherapy regimen Cycle 2 (Day 1-2), Cycle 3 (Day 1) Part 1a - The serum concentration of panitumumab when administered with AMG 706 and either the FOLFIRI or FOLFOX-4 chemotherapy regimen Cycle 1 (Day 1), Cycle 2 (Day 1), Cycle 4 (Day 1) Part 1a - The incidence of HAPA response following panitumumab administration Cycle 1 (Day 1), Cycle 4 (Day 1), End of Study Part 1a - The PK of 5-FU when administered as a part of the FOLFIRI or FOLFOX-4 regimen with panitumumab and AMG 706 Cycle 1 and 2 (Day 3)