A Study Evaluating the Efficacy and Safety of MEGF0444A Dosed to Progression in Combination With Bevacizumab and mFOLFOX-6 in Participants With Previously Untreated Metastatic Colorectal Cancer

NCT ID: NCT01399684

Last Updated: 2016-08-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 127 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2014-02-28

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).

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

5-Fluorouracil

Intervention Type: DRUG

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.

Bevacizumab

Intervention Type: DRUG

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.

Folinic acid

Intervention Type: DRUG

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.

MEGF0444A

Intervention Type: DRUG

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.

Oxaliplatin

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

5-Fluorouracil

Intervention Type: DRUG

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.

Bevacizumab

Intervention Type: DRUG

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.

Folinic acid

Intervention Type: DRUG

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.

Oxaliplatin

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

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.

Interventions

5-Fluorouracil

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.

Intervention Type: DRUG

Bevacizumab

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.

Intervention Type: DRUG

Folinic acid

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.

Intervention Type: DRUG

MEGF0444A

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.

Intervention Type: DRUG

Oxaliplatin

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

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
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, or cirrhosis
• Sensory peripheral neuropathy greater than or equal to (>/=) Grade 2 Bevacizumab-Specific Exclusions
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of bevacizumab or an investigational drug or that may affect the interpretation of the results or render the participant at high risk for treatment complications
• Inadequately controlled hypertension
• Prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Class II or greater congestive heart failure (CHF)
• History of myocardial infarction or unstable angina within 6 months prior to Day 1
• History of stroke or transient ischemic attack (TIA) within 6 months prior to Day 1
• Significant vascular disease within 6 months prior to Day 1
• Evidence of bleeding diathesis or significant coagulopathy
• Current or recent (within 10 days of first dose of study treatment) use of aspirin or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol
• Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purpose
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
• History of abdominal or tracheo-oesophageal fistula or gastrointestinal (GI) perforation within 6 months prior to Day 1
• Clinical signs or symptoms of GI obstruction or a requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
• Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
• Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture 5-Fluorouracil-Specific Exclusion
• Known dihydropyrimidine dehydrogenase deficiency or thymidylate synthase gene polymorphism predisposing the participant for 5-fluorouracil toxicity

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ina Rhee, M.D., Ph.D.

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

Birmingham, Alabama, United States

Scottsdale, Arizona, United States

Bakersfield, California, United States

Fullerton, California, United States

Los Angeles, California, United States

Los Angeles, California, United States

Pasadena, California, United States

San Luis Obispo, California, United States

Aurora, Colorado, United States

Washington D.C., District of Columbia, United States

Jacksonville, Florida, United States

Ocala, Florida, United States

Port Saint Lucie, Florida, United States

Lawrenceville, Georgia, United States

Marietta, Georgia, United States

Harvey, Illinois, United States

Indianapolis, Indiana, United States

Boston, Massachusetts, United States

Boston, Massachusetts, United States

Rochester, Minnesota, United States

Las Vegas, Nevada, United States

Durham, North Carolina, United States

Philadelphia, Pennsylvania, United States

South Brisbane, Queensland, Australia

Woodville South, South Australia, Australia

Footscray, Victoria, Australia

Heidelberg, Victoria, Australia

Melbourne, Victoria, Australia

Brussels, , Belgium

Brussels, , Belgium

Leuven, , Belgium

Gdansk, , Poland

Krakow, , Poland

Poznan, , Poland

Warsaw, , Poland

Barcelona, Barcelona, Spain

Barcelona, Barcelona, Spain

Santander, Cantabria, Spain

Seville, Sevilla, Spain

Valencia, Valencia, Spain

Countries

United States; Australia; Belgium; Poland; Spain

References

Garcia-Carbonero R, van Cutsem E, Rivera F, Jassem J, Gore I Jr, Tebbutt N, Braiteh F, Argiles G, Wainberg ZA, Funke R, Anderson M, McCall B, Stroh M, Wakshull E, Hegde P, Ye W, Chen D, Chang I, Rhee I, Hurwitz H. Randomized Phase II Trial of Parsatuzumab (Anti-EGFL7) or Placebo in Combination with FOLFOX and Bevacizumab for First-Line Metastatic Colorectal Cancer. Oncologist. 2017 Apr;22(4):375-e30. doi: 10.1634/theoncologist.2016-0133. Epub 2017 Mar 8.

Reference Type: DERIVED

PMID: 28275117 (View on PubMed)

Other Identifiers

GO27812

Identifier Type: OTHER

Identifier Source: secondary_id

2011-001867-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MEF4982g

Identifier Type: -

Identifier Source: org_study_id