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

NCT01399684 | Completed Phase 2

• 3 other identifiers: MEF4982gGO278122011-001867-28
• Study Type: interventional
• Target: 127
• Locations: 5 countries
• Sites: 40

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

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version (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)

Secondary Outcomes (12)

• 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)

• 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

• 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)

Study Arms (2)

MEGF0444A + mFOLFOX-6 + Bevacizumab

EXPERIMENTAL

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.

Drug: 5-Fluorouracil; Drug: Bevacizumab; Drug: Folinic acid; Drug: MEGF0444A; Drug: Oxaliplatin

Placebo + mFOLFOX-6 + Bevacizumab

PLACEBO COMPARATOR

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.

Drug: 5-Fluorouracil; Drug: Bevacizumab; Drug: Folinic acid; Drug: Oxaliplatin; Drug: Placebo

Interventions

5-Fluorouracil 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.

MEGF0444A + mFOLFOX-6 + Bevacizumab; Placebo + mFOLFOX-6 + Bevacizumab

Bevacizumab 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.

MEGF0444A + mFOLFOX-6 + Bevacizumab; Placebo + mFOLFOX-6 + Bevacizumab

Folinic acid 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 + mFOLFOX-6 + Bevacizumab; Placebo + mFOLFOX-6 + Bevacizumab

MEGF0444A 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.

MEGF0444A + mFOLFOX-6 + Bevacizumab

Oxaliplatin 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.

MEGF0444A + mFOLFOX-6 + Bevacizumab; Placebo + mFOLFOX-6 + Bevacizumab

Placebo 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.

Placebo + mFOLFOX-6 + Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (40)

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Birmingham, Alabama, 35205, United States

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Scottsdale, Arizona, 85259, United States

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Bakersfield, California, 93309, United States

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Fullerton, California, 92835, United States

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Los Angeles, California, 90095-1772, United States

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Los Angeles, California, 90095, United States

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Pasadena, California, 91107, United States

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San Luis Obispo, California, 93454, United States

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Aurora, Colorado, 80045, United States

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Washington D.C., District of Columbia, 20007, United States

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Jacksonville, Florida, 32224, United States

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Ocala, Florida, 34471, United States

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Port Saint Lucie, Florida, 34952, United States

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Lawrenceville, Georgia, 30045, United States

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Marietta, Georgia, 30060, United States

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Harvey, Illinois, 60426, United States

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Indianapolis, Indiana, 46202, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02115, United States

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Rochester, Minnesota, 55905, United States

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Las Vegas, Nevada, 89148, United States

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Durham, North Carolina, 27710, United States

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Philadelphia, Pennsylvania, 19104, United States

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South Brisbane, Queensland, 4101, Australia

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Woodville South, South Australia, 5011, Australia

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Footscray, Victoria, 3011, Australia

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Heidelberg, Victoria, 3084, Australia

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Melbourne, Victoria, 3168, Australia

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Brussels, 1070, Belgium

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Brussels, 1200, Belgium

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Leuven, 3000, Belgium

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Gdansk, 80-952, Poland

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Krakow, 31-531, Poland

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Poznan, 61-878, Poland

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Warsaw, 02-781, Poland

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Barcelona, Barcelona, 08035, Spain

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Barcelona, Barcelona, 08907, Spain

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Santander, Cantabria, 39008, Spain

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Seville, Sevilla, 41013, Spain

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Valencia, Valencia, 46010, Spain

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Related Publications (1)

• 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.

  PMID: 28275117 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Fluorouracil; Bevacizumab; Leucovorin; parsatuzumab; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Ina Rhee, M.D., Ph.D.

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2011
• First Posted: July 22, 2011
• Study Start: November 1, 2011
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: August 26, 2016

Record last verified: 2016-08

Locations

US (23); PL (4); BE (3); AU (5); ES (5)