Colon Cancer, Rectal Cancer
Conditions
Keywords
AMG 706, Panitumumab
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.
Interventions
DRUGFOLFOX-4
The FOLFOX-4 regimen will be administered every 2 weeks as follows: Day 1: oxaliplatin (ELOXATIN™) 85 mg/m2 IV infusion and leucovorin racemate 200 mg/m2 (or 100 mg/m2 l-LV) IV infusion given over 120 ± 10 minutes at the same time in separate bags using a Y-line, followed by 5-FU 400 mg/m2 IV bolus given over 2 to 4 minutes, followed by 5-FU 600 mg/m2 IV infusion as a 22-hour ± 2 hours continuous infusion Day 2: leucovorin racemate 200 mg/m2 (or 100 mg/m2 l-LV) IV infusion over 120 ± 10 minutes, followed by 5-FU 400 mg/m2 IV bolus given over 2 to 4 minutes, followed
DRUGAMG 706
AMG 706 is a small organic molecule that has been shown in preclinical pharmacology studies to be a potent, oral, multi-kinase inhibitor with anti-angiogenic and anti-tumor activity achieved by selectively inhibiting all known VEGF receptors, PDGF receptor, and Kit.
BIOLOGICALPanitumumab (Part 1a only)
Panitumumab will be administered by IV infusion at a dose of 6 mg/kg on day 1 of each 2-week cycle.
DRUGFOLFIRI
Irinotecan will be administered over 90 minutes ± 15 minutes on day 1 of each 2-week cycle. Leucovorin will be administered over 2 hours ± 15 minutes during the irinotecan infusion but without mixing, immediately followed by a 5-FU bolus and a 5-FU 46-hour ± 2-hour continuous intravenous infusion.
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For complete inclusion and
Exclusion criteria
, please refer to the investigator. Inclusion Criteria 1. Competent to comprehend, sign, and date an Institutional Review Board (IRB) approved informed consent form 2. Diagnosis of metastatic colorectal adenocarcinoma (may have received 1 prior chemotherapy regimen for metastatic CRC) 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 4. Adequate hematological function 5. Adequate renal function 6. Adequate hepatic function 7. Life expectancy of greater than or equal to 3 months as documented by the investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 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) |
| 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) |
| 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) |
| 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 |
Outcome results
None listed