Clinical trial NCT00101894: Safety of AMG 706 Plus Panitumumab Plus Chemotherapy in the Treatment of Subjects With Metastatic Colorectal Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rectal Cancer
Colon Cancer
Keywords: AMG 706
Panitumumab
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2005-01-19
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Exclusion Criteria:

1. More than 1 prior chemotherapy regimen for metastatic CRC
2. Central nervous system (CNS) metastases
3. History of venous thrombosis
4. 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
5. History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on screening chest computed tomograph (CT) scan
6. Average systolic blood pressure \> 150mm Hg or average diastolic blood pressure of \> 90mm Hg
7. Radiotherapy within 28 days of study enrollment or within 14 days of study enrollment for peripheral lesions
8. Prior AMG 706, oral inhibitors of AMG706, panitumumab, or another anti-EGFr monoclonal antibody (mAb) (e.g., cetuximab \[Erbitux®\] or EMD 72000)
9. Systemic chemotherapy within 28 days before study enrollment
10. Major surgery within 28 days or minor surgery within 7days of study enrollment
11. History of life threatening ventricular arrhythmia (eg, sustained ventricular tachycardia)
12. Female and male subjects of childbearing potential not using adequate contraceptive precautions
13. Participation in therapeutic clinical trials within 30 days before study enrollment
14. Not recovered from all previous therapies
15. Clinically significant open would, ulcer or fracture
16. Any co-morbid medical condition that would increase the risk of toxicity

Primary outcomes:
measure: Part 1a - The incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities
timeFrame: First 2 cycles
measure: Part 1b - The incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities
timeFrame: First 2 cycles
measure: 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
timeFrame: Every 8 weeks (+/- 7 days)
Secondary outcomes:
measure: 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
timeFrame: Cycle 1 and 2 (Days 1, 2, 3)
measure: Part 1a - The PK of oxaliplatin when administered as a part of the FOLFOX-4 regimen with panitumumab and AMG 706
timeFrame: Cycle 1 and 2 (Day 1)
measure: Part 1a - The objective tumor response rate (complete and partial response) throughout the study
timeFrame: Every 6 to 8 weeks
measure: Part 1b - The incidence of adverse events and clinical laboratory abnormalities not defined as dose-limiting toxicities
timeFrame: Every visit
measure: Part 1b - The PK of AMG 706 when administered with either the FOLFIRI or FOLFOX-4 chemotherapy regimen
timeFrame: Cycle 2 (Day 1-2), Cycle 3 (Day 1)
measure: Part 1b - The PK of 5-FU when administered as a part of the FOLFIRI or FOLFOX-4 regimen with AMG 706
timeFrame: Cycle 1 and 2 (Day 3)
measure: Part 2 - Duration of response: (Calculated for only those subjects who respond)
timeFrame: Time from first objective tumor response (subsequently confirmed at least 4 weeks later) to objective disease progression or death.
measure: Part 2 - Time-to-progression
timeFrame: Time from first dose of investigational product to objective disease progression or death due to disease progression.
measure: Part 1b - The PK of irinotecan (and its active metabolite SN38) when administered as a part of the FOLFIRI regimen with AMG 706
timeFrame: Cycle 1 and 2 (Days 1, 2, 3)
measure: Part 1b- The PK of oxaliplatin when administered as a part of the FOLFOX-4 regimen with AMG 706
timeFrame: Cycle 1 and 2 (Day 1)
measure: Part 1b - The objective tumor response rate (complete and partial response) throughout the study
timeFrame: Every 8 weeks (+/- 7 days)
measure: Part 2 - Overall survival
timeFrame: 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)
measure: Part 2 - The incidence of adverse events and clinical laboratory abnormalities
timeFrame: Every visit
measure: 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)
timeFrame: Cycles 2, 4, 7, and every 3 subsequent cycles (Day 1)
measure: 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
timeFrame: Day 1 of cycles 1 and 2, and within 7 days of a radiographic assessment
measure: 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)
timeFrame: Day 1 of cycles 1 and 2, and within 7 days of a radiographic assessment
measure: Part 2 - Progression-free survival time
timeFrame: 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.
measure: Part 2 - Incidence of subjects undergoing resection of metastases for curative intent
timeFrame: As needed
measure: Part 1a - The incidence of adverse events and clinical laboratory abnormalities not defined as dose-limiting toxicities
timeFrame: Every visit
measure: Part 1a - The PK of AMG 706 when administered with panitumumab and either the FOLFIRI or FOLFOX-4 chemotherapy regimen
timeFrame: Cycle 2 (Day 1-2), Cycle 3 (Day 1)
measure: Part 1a - The serum concentration of panitumumab when administered with AMG 706 and either the FOLFIRI or FOLFOX-4 chemotherapy regimen
timeFrame: Cycle 1 (Day 1), Cycle 2 (Day 1), Cycle 4 (Day 1)
measure: Part 1a - The incidence of HAPA response following panitumumab administration
timeFrame: Cycle 1 (Day 1), Cycle 4 (Day 1), End of Study
measure: Part 1a - The PK of 5-FU when administered as a part of the FOLFIRI or FOLFOX-4 regimen with panitumumab and AMG 706
timeFrame: Cycle 1 and 2 (Day 3)
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Tebbutt N, Kotasek D, Burris HA, Schwartzberg LS, Hurwitz H, Stephenson J, Warner DJ, Chen L, Hsu CP, Goldstein D. Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer. Cancer Chemother Pharmacol. 2015 May;75(5):993-1004. doi: 10.1007/s00280-015-2694-y. Epub 2015 Mar 15.