This is a Phase II, multicenter, randomized, double-blind, placebo-controlled trial designed to estimate the efficacy of MEGF0444A treatment to disease progression, combined with oxaliplatin + folinic acid + 5-Fluorouracil (mFOLFOX-6) + bevacizumab therapy in participants with metastatic colorectal cancer (CRC).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
127
Participants will receive 5-fluorouracil 400 milligrams per squared meter (mg/m\^2) intravenous (IV) bolus and then 2400 mg/m\^2 as a continuous IV infusion over 46-48 hours on Day 1 of every cycle until disease progression, unacceptable toxicity or at the maximum of 52 cycles, whichever occurs first.
Participants will be administered bevacizumab at a dose of 5 milligrams per kilogram (mg/kg) every 14 days until disease progression or unacceptable toxicity, for a maximum of 52 cycles, whichever occurs first.
Participants will receive folinic acid 400 mg/m\^2 IV infusion over 2 hours on Day 1 of every cycle until disease progression, unacceptable toxicity or at the maximum of 52 cycles, whichever occurs first.
Progression-Free Survival Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 as Determined by the Investigator
Time frame: Screening up to disease progression or death due to any cause, whichever occurs first (assessed every 8-9 weeks after Cycle 1 Day 1 up to approximately 27 months overall)
Percentage of Participants with Objective Response (Complete Response [CR] or Partial Response [PR] Based on RECIST v 1.1 as Determined by the Investigator
Time frame: Screening up to disease progression or death due to any cause, whichever occurs first (assessed every 8 -9 weeks after Cycle 1 Day 1 up to approximately 27 months overall)
Duration of Response Based on RECIST v 1.1 as Determined by the Investigator
Time frame: Screening up to disease progression or death due to any cause, whichever occurs first (assessed every 8 -9 weeks after Cycle 1 Day 1 up to approximately 27 months overall)
Overall Survival (OS)
Time frame: Screening until death (up to approximately 27 months overall)
Percentage of Participants with Adverse Events
Time frame: Up to approximately 27 months overall
Maximum Serum Concentration (Cmax) of MEGF0444A
Time frame: Prior to the first infusion (first infusion being MEGF0444A administration), immediately after end of bevacizumab infusion on Day 1 of Cycles 1, 2; prior to first infusion on Day 1 of Cycles 3 and 8; at study drug discontinuation visit (up to 24 months)
Minimum Serum Concentration (Cmin) of MEGF0444A
Time frame: Prior to the first infusion (first infusion being MEGF0444A administration), immediately after end of bevacizumab infusion on Day 1 of Cycles 1, 2; prior to first infusion on Day 1 of Cycles 3 and 8; at study drug discontinuation visit (up to 24 months)
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Participants will be administered MEGF0444A at a fixed dose of 400 milligrams (mg) IV on Day 1 of Cycle 1, followed by subsequent doses of 400 mg every 14 days until disease progression or unacceptable toxicity, for a maximum of 52 cycles, whichever occurs first.
Participants will receive oxaliplatin 85 mg/m\^2 IV infusion over 90 minutes on Day 1 of every cycle for a maximum of 8 cycles.
Participants will be administered MEGF0444A matching placebo every 14 days until disease progression, unacceptable toxicity or at the maximum of 52 cycles, whichever occurs first.
Unnamed facility
Birmingham, Alabama, United States
Unnamed facility
Scottsdale, Arizona, United States
Unnamed facility
Bakersfield, California, United States
Unnamed facility
Fullerton, California, United States
Unnamed facility
Los Angeles, California, United States
Unnamed facility
Los Angeles, California, United States
Unnamed facility
Pasadena, California, United States
Unnamed facility
San Luis Obispo, California, United States
Unnamed facility
Aurora, Colorado, United States
Unnamed facility
Washington D.C., District of Columbia, United States
...and 30 more locations
Cmax of Bevacizumab
Time frame: Prior to the first infusion (first infusion being MEGF0444A administration), immediately after end of bevacizumab infusion on Day 1 of Cycles 1, 2
Cmin of Bevacizumab
Time frame: Prior to the first infusion (first infusion being MEGF0444A administration), immediately after end of bevacizumab infusion on Day 1 of Cycles 1, 2
Plasma Concentration of 5-Fluorouracil
Time frame: Prior to the first infusion (first infusion being MEGF0444A administration), immediately after end of 5-fluorouracil bolus, 2 hours after end of 5-fluorouracil bolus, 12-24 hours after end of 5-fluorouracil bolus on Day 1 of Cycles 1, 2
Plasma Concentration of Oxaliplatin
Time frame: Prior to the first infusion (first infusion being MEGF0444A administration), 5-10 minutes before end of oxaliplatin infusion, 2 hours after end of 5-fluorouracil bolus, 12-24 hours after end of 5-fluorouracil bolus on Day 1 of Cycles 1, 2
Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to MEGF0444A
Time frame: Pre-dose (within 1 hour before infusion start) on Day 1 of Cycles 1, 3 and 8, (cycle length = 14 days), at study drug discontinuation visit (up to 24 months)
Change From Baseline in ATAs Levels of MEGF0444A
Time frame: Pre-dose (within 1 hour before infusion start) on Day 1 of Cycles 1, 3 and 8, (cycle length = 14 days), at study drug discontinuation visit (up to 24 months)