Study of Tumor Tissue Testing in Selecting Treatment for Patients With Metastatic or Locally Advanced Colorectal Cancer

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal adenocarcinoma meeting 1 of the following criteria:

  • Prior or recurrent primary adenocarcinoma of the colon or rectum with clinical or radiological evidence of locally advanced or metastatic disease
  • Metastatic adenocarcinoma with clinical and/or radiological evidence of colorectal primary tumor

• Inoperable metastatic or locoregional disease

  • Patients suitable for surgical resection of metastatic disease after response to first-line or adjuvant chemotherapy not allowed and should be considered for the New-EPOC trial study
• Unidimensionally measurable disease (according to RECIST criteria)

• Must have completed adjuvant chemotherapy with fluorouracil +/- leucovorin calcium (FU +/- LC), capecitabine, or oxaliplatin combinations in the past 6 months

  • QUASAR 2 patients who have continued bevacizumab for 6 months following completion of chemotherapy are allowed immediately after completion of bevacizumab
• Rectal chemotherapy with FU +/- LC or capecitabine for allowed if completed ≥ 1 month ago
• Single tumor block available
• No brain metastasis

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Alkaline phosphatase ≤ 5 times upper limit of normal (ULN)
• Serum bilirubin ≤ 1.25 times ULN
• AST or ALT ≤ 2.5 times ULN
• Creatinine clearance ≥ 30 mL/min OR GFR ≥ 30 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

• Considered fit to undergo combination chemotherapy, with none of the following conditions:

  • Severe uncontrolled concurrent medical illness likely to interfere with protocol treatments, including any of the following:

    • Poorly controlled angina
    • Uncontrolled hypertension
    • Myocardial infarction within the past 3 months
  • History of severe peptic ulcer disease
  • Any psychiatric or neurological condition that is likely to compromise the patient's ability to give informed consent or to comply with oral medication
  • Nephrotic syndrome
  • Known coagulopathy
• No prior or current malignant disease that, in the judgement of the treating investigator, is likely to interfere with FOCUS 3 treatment or assessment of response
• No known hypersensitivity reactions to any of the components of the study treatments
• No personal or family history suggestive of dihydropyrimidine dehydrogenase (DPD) deficiency or with known DPD deficiency
• No history of uncontrolled seizures, central nervous system disorders, or psychiatric disability judged by the investigator to be clinically significant precluding informed consent
• Not able to attend or comply with treatment or follow-up scheduling

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 4 weeks since prior surgery
• No prior systemic chemotherapy for metastatic disease
• No ongoing therapy with cyclosporin-A
• No ongoing treatment with a contraindicated concomitant medication