A Phase III, Multicenter, Randomized, Active-Controlled Clinical Trial to Evaluate the Efficacy and Safety of rhuMAb VEGF (Bevacizumab) in Combination With Standard Chemotherapy in Subjects With Metastatic Colorectal Cancer

Inclusion Criteria:

- Written informed consent

- Age >=18 years

- Histologically confirmed colorectal carcinoma with evidence of metastases (i.e., by
radiographic imaging or biopsy)

- Ability to tolerate CT contrast dye

- Bi-dimensionally measurable disease (minimum of two lesions)

- ECOG performance status of 0 or 1

- Use of an effective means of contraception in women of childbearing potential

- Life expectancy of >3 months

- Willingness and capability to be accessible for follow-up until death or study
termination by Genentech

Exclusion Criteria:

- Prior chemotherapy other than adjuvant fluoropyrimidines in combination with
leucovorin and/or levamisole

- Administration of adjuvant fluoropyrimidines in combination with leucovorin and/or
levamisole completed <=12 months prior to Day 0

- Administration of fluoropyrimidines as a radiosensitizer during pelvic radiotherapy
for rectal cancer completed <=12 months prior to Day 0

- Prior radiotherapy to a measurable, metastatic lesion(s) to be used to measure
response

- Radiation therapy within 14 days prior to Day 0

- Prior biotherapy for colorectal cancer

- Evidence of clinically detectable ascites on Day 0

- Other invasive malignancies within 5 years prior to Day 0 (other than basal cell
carcinoma of the skin)

- History or evidence upon physical examination of CNS disease (e.g., primary brain
tumor, seizures not controlled with standard medical therapy, any brain metastases,
or history of stroke)

- Active infection requiring parenteral antibiotics on Day 0

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0, or anticipation of need for major surgical procedure during the
course of the study; fine needle aspirations within 7 days prior to Day 0

- Current or recent (within the 10 days prior to Day 0) use of full-dose oral or
parenteral anticoagulants (except as required to maintain patency of preexisting,
permanent indwelling IV catheters) or thrombolytic agent (for subjects receiving
warfarin, international normalized ratio [INR] of <1.5; appropriate use of heparin
should be discussed with the Medical Monitor)

- Chronic, daily treatment with aspirin (>325 mg/day) or nonsteroidal anti-inflammatory
medications (of the kind known to inhibit platelet function at doses used to treat
chronic inflammatory diseases)

- Pregnancy (positive pregnancy test) or lactation

- Proteinuria at baseline or clinically significant impairment of renal function

- Serious, nonhealing wound, ulcer, or bone fracture

- Evidence of bleeding diathesis or coagulopathy

- Current or recent (within the 28 days prior to Day 0) participation in another
experimental drug study

- Clinically significant cardiovascular disease (e.g., uncontrolled hypertension,
myocardial infarction, unstable angina), New York Heart Association (NYHA) Grade II
or greater congestive heart failure, serious cardiac arrhythmia requiring medication,
or Grade II or greater peripheral vascular disease within 1 year prior to Day 0

- Screening clinical laboratory values: *ANC of <1500/uL; *Platelet count of
<75,000/uL; *INR of >=1.5; *Total bilirubin of >1.6 mg/dL; *AST or ALT >=5 times
upper limit of normal for subjects with documented liver metastases (>2.5 times the
upper limit of normal for subjects without evidence of liver metastases); *Serum
creatinine of >2.0 mg/dL; *Hemoglobin of <9 gm/dL (may be transfused to maintain or
exceed this level)

- History of other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates use of an investigational drug or that might affect
interpretation of the results of the study or render the subject at high risk from
treatment complications