Phase II Study of Oxaliplatin, Capecitabine and Bevacizumab as First Line Treatment for Patients With Advanced Colorectal Cancer
- Histologically or cytologically confirmed metastatic or recurrent colorectal tumors
with no previous treatment for advanced disease.
- Age greater than or equal to 18 years
- SWOG performance status 0-1.
- At least one measurable lesion according to the RECIST criteria which has not been
irradiated (i.e. newly arising lesions in previously irradiated areas are accepted).
Minimum indicator lesion size: > 10 mm measured by spiral CT or >20mm measured by
- Have a negative serum pregnancy test within 7 days prior to initiation of
chemotherapy (female patients of childbearing potential).
- Availability of tumor biopsy (paraffin embedded or fresh frozen) at the time of
diagnosis and/or prior to study entry is required.
- Patients must agree to have a 20 cc blood sample drawn in addition to routine labs
with each cycle of chemotherapy.
- Pregnant or lactating woman.
- Life expectancy < 3 months.
- Serious, uncontrolled, concurrent infection(s) or illness(es)
- Any prior oxaliplatin treatment, with the exception of adjuvant therapy given > 12
months prior to the beginning of study therapy
- Prior unanticipated severe reaction to fluoropyrimidine therapy, known
hypersensitivity to 5-fluorouracil, or known DPD deficiency
- Prior unanticipated severe reaction or hypersensitivity to platinum based compounds.
- Treatment for other carcinomas within the last five years, except cured non-melanoma
skin and treated in-situ cervical cancer.
- Current, recent (within 4 weeks of first infusion on this study) or planned
participation in an investigational drug study.
- Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic
coronary artery disease and cardiac arrhythmias not well controlled with medication)
within the last 6 months.
- History of clinically significant interstitial lung disease and/or pulmonary
- History of persistent neurosensory disorder including but not limited to peripheral
- Presence of central nervous system or brain mets.
- Major surgery, 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
- Lack of physical integrity of the upper gastrointestinal tract or malabsorption
- Any of the following laboratory values:
- Abnormal hematologic values (neutrophils < 1.5 x 109/L, platelet count <
100 x 109/L)
- Urine protein: creatinine ratio >/= 1.0 Impaired renal function with estimated
creatinine clearance < 30 ml/min as calculated with Cockroft et Gault equation:
- Serum bilirubin > 1.5 x upper normal limit. ALT, AST > 2.5 x upper normal limit
(or > 5 x upper normal limit in the case of liver metastases)
- Alkaline phosphatase > 2.5 x upper normal limit (or > 5 x upper normal limit in
the case of liver metastases or > 10 x upper normal limit in the case of bone
- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
prior to Day 0
- Blood pressure > 150/100 mmHg
- Unstable angina
- New York Heart Association (NYHA) Grade II or greater congestive heart failure
- History of myocardial infarction or stroke within 6 months
- Clinically significant peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy
- History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess
within 28 days prior to Day 0.
- Serious, non-healing wound, ulcer or bone fracture
- Carcinoma of any histology in close proximity to a major vessel, cavitation or
history of hemoptysis.
- Completion of previous adjuvant chemotherapy regimen < four weeks prior to the start
of study treatment (within six weeks of study treatment for mitomycin C and
nitroureas), or with related toxicities unresolved prior to the start of study