An Open-Label, Dose-Finding Study to Evaluate the Safety of AMG 706 Plus Panitumumab Plus Chemotherapy in the Treatment of Subjects With Metastatic Colorectal Cancer

简要总结

主要结局

次要结局

• Part 1a - The objective tumor response rate (complete and partial response) throughout the study(Every 6 to 8 weeks)
• 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 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))