A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of MEGF0444A Dosed to Progression in Combination With Bevacizumab and FOLFOX in Patients With Previously Untreated Metastatic Colorectal Cancer
Overview
- Phase
- Phase 2
- Intervention
- 5-Fluorouracil
- Conditions
- Metastatic Colorectal Cancer
- Sponsor
- Genentech, Inc.
- Enrollment
- 127
- Primary Endpoint
- Progression-Free Survival Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 as Determined by the Investigator
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed CRC not amenable to potentially curative resection with at least one measurable metastatic lesion, as defined by RECIST v1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate hematologic and end organ function
- •For female participants of childbearing potential and male participants with partners of childbearing potential, agreement to use a highly effective form of contraception and to continue its use for 6 months after the last dose of study treatment
- •Negative serum pregnancy test within 7 days prior to starting study treatment in premenopausal women and women less than (\<) 2 years after the onset of menopause
Exclusion Criteria
- •Disease-specific exclusions
- •Any prior systemic therapy (including chemotherapy, antibody therapy, tyrosine kinase inhibitors, radiotherapy, immunotherapy, hormonal therapy or investigational therapy) before Day 1 of Cycle 1 for treatment of CRC General Medical Exclusions
- •Malignancies other than CRC within 5 years prior to randomization, except for those with a negligible risk of metastasis or death
- •Radiotherapy to any site for any reason within 28 days prior to Day 1 of Cycle 1
- •Clinically detectable third-space fluid collections that cannot be controlled by drainage or other procedures prior to study entry
- •Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to Day 1 of Cycle 1
- •Lactating women
- •Clinically suspected or confirmed central nervous system (CNS) metastases or carcinomatous meningitis
- •Active infection requiring IV antibiotics
- •Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs, inhaled corticosteroids, or the equivalent of less than or equal to (\</=) 10 milligrams per day (mg/day) prednisone
Arms & Interventions
MEGF0444A + mFOLFOX-6 + Bevacizumab
Participants will receive MEGF0444A + mFOLFOX-6 (oxaliplatin, folinic acid, and 5-fluorouracil) regimen + bevacizumab. Participants will receive oxaliplatin for up to 8 cycles (Cycle = 14 days) and 5-fluorouracil, folinic acid, bevacizumab and MEGF0444A will be administered until disease progression or unacceptable toxicity for a maximum of up to 52 cycles.
Intervention: 5-Fluorouracil
MEGF0444A + mFOLFOX-6 + Bevacizumab
Participants will receive MEGF0444A + mFOLFOX-6 (oxaliplatin, folinic acid, and 5-fluorouracil) regimen + bevacizumab. Participants will receive oxaliplatin for up to 8 cycles (Cycle = 14 days) and 5-fluorouracil, folinic acid, bevacizumab and MEGF0444A will be administered until disease progression or unacceptable toxicity for a maximum of up to 52 cycles.
Intervention: Bevacizumab
MEGF0444A + mFOLFOX-6 + Bevacizumab
Participants will receive MEGF0444A + mFOLFOX-6 (oxaliplatin, folinic acid, and 5-fluorouracil) regimen + bevacizumab. Participants will receive oxaliplatin for up to 8 cycles (Cycle = 14 days) and 5-fluorouracil, folinic acid, bevacizumab and MEGF0444A will be administered until disease progression or unacceptable toxicity for a maximum of up to 52 cycles.
Intervention: Folinic acid
MEGF0444A + mFOLFOX-6 + Bevacizumab
Participants will receive MEGF0444A + mFOLFOX-6 (oxaliplatin, folinic acid, and 5-fluorouracil) regimen + bevacizumab. Participants will receive oxaliplatin for up to 8 cycles (Cycle = 14 days) and 5-fluorouracil, folinic acid, bevacizumab and MEGF0444A will be administered until disease progression or unacceptable toxicity for a maximum of up to 52 cycles.
Intervention: MEGF0444A
MEGF0444A + mFOLFOX-6 + Bevacizumab
Participants will receive MEGF0444A + mFOLFOX-6 (oxaliplatin, folinic acid, and 5-fluorouracil) regimen + bevacizumab. Participants will receive oxaliplatin for up to 8 cycles (Cycle = 14 days) and 5-fluorouracil, folinic acid, bevacizumab and MEGF0444A will be administered until disease progression or unacceptable toxicity for a maximum of up to 52 cycles.
Intervention: Oxaliplatin
Placebo + mFOLFOX-6 + Bevacizumab
Participants will receive MEGF0444A matching placebo + mFOLFOX-6 regimen + bevacizumab. Participants will receive oxaliplatin for up to 8 cycles and 5-fluorouracil, folinic acid, bevacizumab and placebo will be administered until disease progression or unacceptable toxicity for a maximum of up to 52 cycles.
Intervention: 5-Fluorouracil
Placebo + mFOLFOX-6 + Bevacizumab
Participants will receive MEGF0444A matching placebo + mFOLFOX-6 regimen + bevacizumab. Participants will receive oxaliplatin for up to 8 cycles and 5-fluorouracil, folinic acid, bevacizumab and placebo will be administered until disease progression or unacceptable toxicity for a maximum of up to 52 cycles.
Intervention: Bevacizumab
Placebo + mFOLFOX-6 + Bevacizumab
Participants will receive MEGF0444A matching placebo + mFOLFOX-6 regimen + bevacizumab. Participants will receive oxaliplatin for up to 8 cycles and 5-fluorouracil, folinic acid, bevacizumab and placebo will be administered until disease progression or unacceptable toxicity for a maximum of up to 52 cycles.
Intervention: Folinic acid
Placebo + mFOLFOX-6 + Bevacizumab
Participants will receive MEGF0444A matching placebo + mFOLFOX-6 regimen + bevacizumab. Participants will receive oxaliplatin for up to 8 cycles and 5-fluorouracil, folinic acid, bevacizumab and placebo will be administered until disease progression or unacceptable toxicity for a maximum of up to 52 cycles.
Intervention: Oxaliplatin
Placebo + mFOLFOX-6 + Bevacizumab
Participants will receive MEGF0444A matching placebo + mFOLFOX-6 regimen + bevacizumab. Participants will receive oxaliplatin for up to 8 cycles and 5-fluorouracil, folinic acid, bevacizumab and placebo will be administered until disease progression or unacceptable toxicity for a maximum of up to 52 cycles.
Intervention: Placebo
Outcomes
Primary Outcomes
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)
Secondary Outcomes
- Percentage of Participants with Objective Response (Complete Response [CR] or Partial Response [PR] Based on RECIST v 1.1 as Determined by the Investigator(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))
- Maximum Serum Concentration (Cmax) of MEGF0444A(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(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))
- Cmax of Bevacizumab(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(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)
- Cmin of Bevacizumab(Prior to the first infusion (first infusion being MEGF0444A administration), immediately after end of bevacizumab infusion on Day 1 of Cycles 1, 2)
- Duration of Response Based on RECIST v 1.1 as Determined by the Investigator(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)(Screening until death (up to approximately 27 months overall))
- Percentage of Participants with Adverse Events(Up to approximately 27 months overall)
- Plasma Concentration of Oxaliplatin(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(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(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))