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

A Phase II Study of Oral Xeloda (Capecitabine) in Combination With Intravenous Irinotecan for Patients With Locally Advanced and/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.

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