Study of Bevacizumab + mFOLFOX6 Versus Bevacizumab + FOLFIRI With Biomarker Stratification in Participants With Previously Untreated Metastatic Colorectal Cancer (mCRC)
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: 5-Fluorouracil; Bevacizumab; Irinotecan; Leucovorin; Oxaliplatin; Capecitabine
Intervention description: 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 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 180 mg/m^2 via IV infusion over 2 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.; 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 85 mg/m^2 via IV infusion over 2 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.; 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 MeSH terms: Leucovorin; Bevacizumab; Capecitabine; Fluorouracil; Oxaliplatin; Irinotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 376.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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