• Overall response rate as assessed by RECIST criteria [ Designated as safety issue: No ]
  

• Progression-free survival [ Designated as safety issue: No ]
  
• Duration of response [ Designated as safety issue: No ]
  
• Time to treatment failure [ Designated as safety issue: No ]
  
• Overall survival [ Designated as safety issue: No ]
  
• Time to response [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Define the dose-limiting toxicity and maximum tolerated dose of gemcitabine hydrochloride when administered with capecitabine and oxaliplatin as second-line therapy in patients with advanced colorectal cancer previously treated with irinotecan hydrochloride. (Phase I)
• Determine the recommended phase II dose of gemcitabine hydrochloride in these patients. (Phase I)
• Assess overall response rate in patients treated with this regimen. (Phase II)

Secondary

• Assess the progression-free survival of patients treated with this regimen. (Phase II)
• Assess the time to treatment failure, duration of response, and time to response in patients treated with this regimen. (Phase II)
• Assess the overall survival of patients treated with this regimen. (Phase II)
• Assess the safety of this regimen in these patients. (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study of gemcitabine hydrochloride, followed by a phase II, open-label study.

• Phase I: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, oral capecitabine twice daily on days 1-14, and oxaliplatin IV over 2 hours on day 1. Courses repeat every 21 days.

Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride until the maximum tolerated dose (MTD) is determined.

• Phase II: Patients receive gemcitabine hydrochloride at the MTD determined in phase I and capecitabine and oxaliplatin as in phase I.

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced colorectal adenocarcinoma
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
• Must have received prior irinotecan hydrochloride with a progression-free interval of < 3 months
• No symptomatic brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 3 months
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 2 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN (5 times ULN if liver metastases are present)
• Creatinine ≤ 1.5 times ULN
• No significant cardiac abnormalities by ECG
• No known hypersensitivity to the study drugs or any of their components
• No myocardial infarction within the past 12 months
• No uncontrolled congestive heart failure
• No cardiovascular disorder ≥ grade 3 despite treatment
• No other malignancies or invasive carcinomas diagnosed within the past 5 years, except for adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix
• No significant disease, that in the opinion of the investigator, would preclude study treatment (e.g., active infections, interstitial lung disease, or peripheral neuropathy)
• No history of significant neurological or psychiatric disorder (e.g., dementia, seizures, or bipolar disorder)
• No legal incapacity or limited legal capacity that would preclude study participation

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from all prior therapy
• More than 30 days since prior participation in another clinical trial
• No concurrent warfarin, phenprocoumon, phenytoin, or sorivudine