A Randomized Phase II Study of Bevacizumab/mFOLFOX6 Versus Bevacizumab/Folfiri With Biomarker Stratification in Patients With Previously Untreated Metastatic Colorectal Cancer

Inclusion Criteria:

Inclusion criteria:

- Histologically or cytologically confirmed colorectal cancer (CRC) with at least one
measurable metastatic lesion by RECIST, v1.1

- Archival tumor tissue sample for ERCC-1 assessment (stratification) 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.

- Patients with treated brain metastases are eligible for study participation.
Patients 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 patients should not be pregnant or breast-feeding. Female patients 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 patients with an intact uterus (unless
amenorrhoeic for the last 24 months) must have a negative serum pregnancy test within
7 days prior to randomization into the study.

- Male patients 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 metastatic CRC

- 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 metastatic CRC 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