Capecitabine and Irinotecan in Treating Patients With Locally Advanced, Recurrent, or Metastatic Colorectal Cancer

PURPOSE: Phase II trial to study the effectiveness of combining capecitabine and irinotecan in treating patients who have locally advanced, recurrent, or metastatic colorectal cancer.

OBJECTIVES:

Primary:

* Determine the overall objective response rate in patients with locally advanced, locally recurrent, or metastatic colorectal cancer treated with capecitabine and irinotecan.

Secondary:

* Determine the time to treatment failure, time to overall response, duration of overall response, duration of overall complete response, and time to progression in patients treated with this regimen.
* Determine the 1-year survival and overall survival of patients treated with this regimen.
* Determine the toxicity and safety profile of this regimen in these patients.
* Determine the feasibility of predicting responses to this regimen by the molecular profile of tumor tissue in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral capecitabine twice daily on days 2-15 and irinotecan IV over 90 minutes on days 1 and 8. Treatment repeats every 3 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients maintaining a response or stable disease after 12 courses may continue treatment at the discretion of the investigator.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 65 patients will be accrued for this study within 9 months.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed locally advanced, locally recurrent, or metastatic colorectal adenocarcinoma
* At least 1 measurable lesion

  * At least 10 mm by spiral CT scan
  * At least 20 mm by conventional techniques
  * Bone metastases, ascites, or pleural effusions are not considered measurable disease
* No evidence of CNS metastases

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Karnofsky 80-100%

Life expectancy:

* Not specified

Hematopoietic:

* Neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin no greater than 1.25 times upper limit of normal (ULN)
* ALT and AST no greater than 2.5 times ULN (5 times ULN if liver metastases present)
* Alkaline phosphatase no greater than 2.5 times ULN (5 times ULN if liver metastases present or 10 times ULN if bone metastases present)
* No known Gilbert's disease

Renal:

* Creatinine no greater than 1.5 times ULN
* Creatinine clearance at least 50 mL/min

Cardiovascular:

* No clinically significant cardiac disease
* No congestive heart failure
* No symptomatic coronary artery disease
* No cardiac arrhythmias uncontrolled with medication
* No myocardial infarction within the past 12 months

Gastrointestinal:

* Able to swallow tablets
* No lack of physical integrity of the upper gastrointestinal tract
* No malabsorption syndrome

Other:

* No prior unanticipated severe reaction to fluoropyrimidine therapy
* No hypersensitivity to fluorouracil
* No history of uncontrolled seizures or CNS disorders
* No psychological illness or condition that would preclude study entry
* No other malignancy within the past 5 years except curatively treated basal cell skin cancer or carcinoma in situ of the cervix
* No serious infection
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 12 months since prior neoadjuvant or adjuvant, active or passive immunotherapy
* No concurrent active or passive immunotherapy (e.g., 17-1A antibody) for colon cancer
* No concurrent prophylactic hematopoietic growth factors

Chemotherapy:

* At least 12 months since prior neoadjuvant or adjuvant cytotoxic chemotherapy
* No prior chemotherapy for metastatic colorectal cancer
* No prior therapy with irinotecan or capecitabine
* No other concurrent cytotoxic agents

Endocrine therapy:

* Not specified

Radiotherapy:

* At least 4 weeks since prior radiotherapy
* No prior radiotherapy to measurable lesion (newly arising lesions in a previously irradiated area allowed)
* No concurrent radiotherapy

Surgery:

* At least 4 weeks since prior major surgery and recovered
* No prior organ allograft

Other:

* At least 4 weeks since prior participation in an investigational drug study
* No other concurrent investigational drugs