Study of Bevacizumab + mFOLFOX6 Versus Bevacizumab + FOLFIRI With Biomarker Stratification in Participants With Previously Untreated Metastatic Colorectal Cancer (mCRC)

NCT ID: NCT01374425

Last Updated: 2016-08-11

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

376 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-08-31

Study Completion Date

2015-07-31

Brief Summary

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This will be a randomized, open-label, multicenter, Phase II study with primary objectives to assess whether expression of select chemotherapy markers is associated with progression-free survival (PFS) in participants treated with bevacizumab plus leucovorin, 5-fluorouracil, and oxaliplatin (mFOLFOX6) or bevacizumab plus leucovorin, 5-fluorouracil, and irinotecan (FOLFIRI). The study population will consist of participants with first-line mCRC.

Detailed Description

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Conditions

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Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Bevacizumab + mFOLFOX6

Participants will receive bevacizumab plus mFOLFOX6 by intravenous (IV) infusion on Day 1 of each 2-week cycle until disease progression or unacceptable toxicity. Participants may be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin, with bevacizumab continued in 3-week cycles.

Group Type EXPERIMENTAL

5-Fluorouracil

Intervention Type DRUG

5-Fluorouracil 400 milligrams per meter-squared (mg/m\^2) by IV bolus and subsequent 2400 mg/m\^2 by IV infusion over 46 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.

Bevacizumab

Intervention Type DRUG

Bevacizumab 5 milligrams per kilogram (mg/kg) of body weight via IV infusion will be administered every 2 weeks until disease progression or unacceptable toxicity. If participants are discontinued from oxaliplatin or irinotecan due to unacceptable toxicity, bevacizumab may be given in 3-week cycles with capecitabine.

Leucovorin

Intervention Type DRUG

Leucovorin 400 mg/m\^2 or dose deemed appropriate by Investigator via IV infusion over 2 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.

Oxaliplatin

Intervention Type DRUG

Oxaliplatin 85 mg/m\^2 via IV infusion over 2 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.

Capecitabine

Intervention Type DRUG

Capecitabine 850 or 1000 mg/m\^2 may be offered in the event of unacceptable toxicity to oxaliplatin or irinotecan, to be given orally twice a day on Days 1 to 14 in 3-week cycles.

Bevacizumab + FOLFIRI

Participants will receive bevacizumab plus FOLFIRI by IV infusion on Day 1 of each 2-week cycle until disease progression or unacceptable toxicity. Participants may be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan, with bevacizumab continued in 3-week cycles.

Group Type EXPERIMENTAL

5-Fluorouracil

Intervention Type DRUG

5-Fluorouracil 400 milligrams per meter-squared (mg/m\^2) by IV bolus and subsequent 2400 mg/m\^2 by IV infusion over 46 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.

Bevacizumab

Intervention Type DRUG

Bevacizumab 5 milligrams per kilogram (mg/kg) of body weight via IV infusion will be administered every 2 weeks until disease progression or unacceptable toxicity. If participants are discontinued from oxaliplatin or irinotecan due to unacceptable toxicity, bevacizumab may be given in 3-week cycles with capecitabine.

Irinotecan

Intervention Type DRUG

Irinotecan 180 mg/m\^2 via IV infusion over 2 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.

Leucovorin

Intervention Type DRUG

Leucovorin 400 mg/m\^2 or dose deemed appropriate by Investigator via IV infusion over 2 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.

Capecitabine

Intervention Type DRUG

Capecitabine 850 or 1000 mg/m\^2 may be offered in the event of unacceptable toxicity to oxaliplatin or irinotecan, to be given orally twice a day on Days 1 to 14 in 3-week cycles.

Interventions

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5-Fluorouracil

5-Fluorouracil 400 milligrams per meter-squared (mg/m\^2) by IV bolus and subsequent 2400 mg/m\^2 by IV infusion over 46 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.

Intervention Type DRUG

Bevacizumab

Bevacizumab 5 milligrams per kilogram (mg/kg) of body weight via IV infusion will be administered every 2 weeks until disease progression or unacceptable toxicity. If participants are discontinued from oxaliplatin or irinotecan due to unacceptable toxicity, bevacizumab may be given in 3-week cycles with capecitabine.

Intervention Type DRUG

Irinotecan

Irinotecan 180 mg/m\^2 via IV infusion over 2 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.

Intervention Type DRUG

Leucovorin

Leucovorin 400 mg/m\^2 or dose deemed appropriate by Investigator via IV infusion over 2 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.

Intervention Type DRUG

Oxaliplatin

Oxaliplatin 85 mg/m\^2 via IV infusion over 2 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.

Intervention Type DRUG

Capecitabine

Capecitabine 850 or 1000 mg/m\^2 may be offered in the event of unacceptable toxicity to oxaliplatin or irinotecan, to be given orally twice a day on Days 1 to 14 in 3-week cycles.

Intervention Type DRUG

Other Intervention Names

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Avastin

Eligibility Criteria

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Inclusion Criteria

* Histologically or cytologically confirmed colorectal cancer (CRC) with at least one measurable metastatic lesion by RECIST Version 1.1
* Archival tumor tissue sample must be requested and available prior to study entry. If no archival tumor tissue sample is available, a fresh biopsy tissue sample must be obtained but should be discussed first with the medical monitor. A copy of the local pathology report must be submitted along with the specimens.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Participants with treated brain metastases are eligible for study participation. Participants may not receive ongoing treatment with steroids at Screening. Anticonvulsants (at stable dose) are allowed. Treatment for brain metastases may be whole-brain radiotherapy, radiosurgery, neurosurgery, or a combination as deemed appropriate by the treating physician. Radiotherapy and stereotactic radiosurgery must be completed at least 28 days prior to randomization.
* Female participants should not be pregnant or breastfeeding. Female participants with childbearing potential should agree to use effective, non-hormonal means of contraception during the study and for a period of at least 6 months following the last administration of study drugs. Female participants with an intact uterus (unless amenorrheic for the last 24 months) must have a negative serum pregnancy test within 7 days prior to randomization into the study.
* Male participants must agree to use effective contraception during the study and for a period of at least 6 months following the last administration of study drugs, even if they have been surgically sterilized.

Exclusion Criteria

* Any prior systemic treatment for mCRC
* Adjuvant chemotherapy for CRC completed \<12 months
* Evidence of Gilbert's syndrome or of homozygosity for the UGT1A1\*28 allele
* Known positivity for human immunodeficiency virus (HIV)
* Malignancies other than mCRC within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, and ductal carcinoma in situ treated surgically with curative intent
* Radiotherapy to any site for any reason within 28 days prior to randomization, except for palliative radiotherapy to bone lesions within 14 days prior to randomization
* 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 investigational drug trial within 28 days prior to randomization
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christiane Langer, M.D.

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

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Birmingham, Alabama, United States

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Little Rock, Arkansas, United States

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Bellflower, California, United States

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Duarte, California, United States

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Fountain Valley, California, United States

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Fresno, California, United States

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Hayward, California, United States

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Los Angeles, California, United States

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Oakland, California, United States

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Pleasant Hill, California, United States

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Roseville, California, United States

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Sacramento, California, United States

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Sacramento, California, United States

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San Francisco, California, United States

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San Jose, California, United States

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Santa Clara, California, United States

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South San Francisco, California, United States

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Vallejo, California, United States

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Walnut Creek, California, United States

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Denver, Colorado, United States

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Stamford, Connecticut, United States

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Trumbull, Connecticut, United States

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Hollywood, Florida, United States

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Jacksonville, Florida, United States

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Miami, Florida, United States

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Port Saint Lucie, Florida, United States

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Boise, Idaho, United States

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Joliet, Illinois, United States

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Maywood, Illinois, United States

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Peoria, Illinois, United States

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Goshen, Indiana, United States

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Indianapolis, Indiana, United States

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Terre Haute, Indiana, United States

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Fairway, Kansas, United States

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Elizabethtown, Kentucky, United States

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Scarborough, Maine, United States

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Burlington, Massachusetts, United States

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Billings, Montana, United States

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Lincoln, Nebraska, United States

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Cherry Hill, New Jersey, United States

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Manasquan, New Jersey, United States

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Albuquerque, New Mexico, United States

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Albuquerque, New Mexico, United States

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Albuquerque, New Mexico, United States

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Farmington, New Mexico, United States

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Las Cruces, New Mexico, United States

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Santa Fe, New Mexico, United States

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Rochester, New York, United States

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Durham, North Carolina, United States

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Greensboro, North Carolina, United States

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High Point, North Carolina, United States

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Washington, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Columbus, Ohio, United States

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Toledo, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Dunmore, Pennsylvania, United States

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Media, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Charleston, South Carolina, United States

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Corpus Christi, Texas, United States

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Houston, Texas, United States

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Madison, Wisconsin, United States

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Wauwatosa, Wisconsin, United States

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Edmonton, Alberta, Canada

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Tallinn, , Estonia

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Tartu, , Estonia

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Cork, , Ireland

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Dublin, , Ireland

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Galway, , Ireland

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Oslo, , Norway

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Coimbra, , Portugal

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Lisbon, , Portugal

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Porto, , Portugal

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Aarau, , Switzerland

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Basel, , Switzerland

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Lucerne, , Switzerland

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Zurich, , Switzerland

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Countries

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United States Canada Estonia Ireland Norway Portugal Switzerland

Other Identifiers

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2011-004755-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ML25710

Identifier Type: -

Identifier Source: org_study_id

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