Metastatic Colorectal Cancer, Colon Cancer, Colorectal Cancer, Rectal Cancer
Conditions
Keywords
Colon Cancer, Colorectal Cancer, Rectal Cancer, AMG 655, Bevacizumab, Modified FOLFOX6, mFOLFOX6, FOLFOX
Brief summary
This phase 1/2, multi-center, randomized, double-blind, placebo-controlled trial is designed to evaluate the efficacy and safety of AMG 655 when combined with mFOLFOX6 and bevacizumab compared with mFOLFOX6 and bevacizumab alone in subjects with previously untreated metastatic colorectal cancer (CRC). The clinical benefit of AMG 655 in combination with mFOLFOX6 and bevacizumab will be measured by progression-free survival, objective response rate, time to response, duration of response, and overall survival. This study is also designed to evaluate the safety and tolerability of AMG 655 in combination with mFOLFOX6 and bevacizumab and to evaluate anti-AMG 655 antibody formation and the pharmacokinetics of AMG 655.
Interventions
DRUGPlacebo
Inactive dummy AMG 655 (to maintain blind)
DRUGAMG 655
AMG 655 is an investigational, fully human monoclonal agonist antibody that selectively binds to Death Receptor-5 (DR5).
DRUGModified FOLFOX6
Combination treatment comprising oxaliplatin (85 mg/m2), leucovorin (400 mg/m2) and bolus 5-FU (400 mg/m2) and continuous IV 5-FU (2400 mg/m2)\] administered by intravenous infusion once every 14 days (+3 days)
DRUGBevacizumab
Bevacizumab will be administered at a dose of 5 mg/kg by intravenous infusion on day 1 of each 14 day cycle (+3 days).
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum. * Subjects with measurable or unmeasurable disease * Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 * Men or women at least 18 years of age * Adequate hematologic, renal, hepatic and coagulation function
Exclusion criteria
* History or known presence of central nervous system (CNS) metastases * Prior chemotherapy or other systemic therapy for advanced or metastatic CRC * Any investigational agent or therapy for advanced or metastatic CRC * Clinically significant cardiac disease * Clinically significant peripheral neuropathy * Active inflammatory bowel disease * Recent gastrointestinal ulcer or hemorrhage * Recent arterial thrombotic event or pulmonary embolus * Recent history of clinically significant bleeding, bleeding diathesis, or coagulopathy * Recent major surgical procedure or not yet recovered from major surgery
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival | Length of study |
Secondary
| Measure | Time frame |
|---|---|
| Duration of response | Length of study |
| Time-to-response | Length of study |
| Objective response rate | Length of study |
| AMG 655 pharmacokinetic parameters | Length of study |
| The incidence of anti-AMG 655 antibody formation | Length of study |
| Overall survival | Length of study |
Countries
United States
Outcome results
None listed