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

OBJECTIVES:

Primary

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

Secondary

• Determine the time to progression in patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Determine the overall survival of patients treated with this regimen.
• Determine the time to treatment failure in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral celecoxib twice daily on days -7 to 21 during course 1 and on days 1-21 in all subsequent courses. Patients also receive oral capecitabine twice daily on days 1-14 and irinotecan IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete or partial response after 4 courses may temporarily discontinue treatment for no more than 4 weeks.

After completion of study treatment, patients are followed every 6 months for survival.

PROJECTED ACCRUAL: A total of 21-44 patients will be accrued for this study within 7-18 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the colon or rectum

• Locally recurrent or metastatic disease
• Measurable disease, defined as ≥ 1 measurable lesion ≥ 20 mm by conventional CT scan OR ≥ 10 mm by spiral CT scan

• Bone metastases, ascites, and pleural effusion are not considered measurable disease
• Measurable lesions must be located outside a previously irradiated field

PATIENT CHARACTERISTICS:

Performance status

• SWOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin normal
• No Gilbert's disease

Renal

• Creatinine clearance > 50 mL/min

Cardiovascular

• No clinically significant cardiac disease that is not well controlled by medication, including any of the following conditions:

• Congestive heart failure
• Symptomatic coronary artery disease
• Cardiac arrhythmias
• No myocardial infarction within the past year

Gastrointestinal

• Must have a physically intact upper gastrointestinal tract
• Able to swallow tablets
• No history of peptic ulcer disease or gastroesophageal reflux
• No malabsorption syndrome

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known HIV positivity
• No asthma, urticaria, or allergic-type reaction after prior treatment with aspirin or other nonsteroidal anti-inflammatory drugs
• No other malignancy except curatively treated cancer with no evidence of active disease
• No unresolved bacterial infection requiring antibiotics
• No other serious infection
• No known allergy to study drugs or sulfa drugs

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for colorectal cancer

• Patients relapsing > 6 months after completion of prior adjuvant chemotherapy allowed
• No other concurrent anticancer chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy
• No concurrent anticancer radiotherapy

Surgery

• Recovered from prior surgery
• No concurrent anticancer surgery

Other

• Prior celecoxib for nonmalignant disorders allowed
• No other concurrent cyclooxygenase-2 inhibitors or nonsteroidal anti-inflammatory drugs, including any of the following:

• Rofecoxib
• Ibuprofen
• Naproxen
• Etodolac
• Oxaprozin
• Diflunisal
• Nabumetone
• Tolmetin