OBJECTIVES:

• Determine the maximum tolerated dose of irinotecan, oxaliplatin, and capecitabine in patients with unresectable solid tumors.
• Determine the activity of this regimen in these patients.
• Determine the toxicity profile, especially pertaining to hematologic and gastrointestinal toxicity, of this regimen in these patients.

OUTLINE: This is a dose-escalation study. Patients are stratified according to UGT1A1 genotype (6/6 vs 6/7 [closed to accrual as of 8/24/06] vs 7/7).

Patients receive irinotecan IV over 90 minutes and oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 2-15. Courses repeat every 3 weeks.

Cohorts of 3-6 patients receive escalating doses of irinotecan, oxaliplatin, and capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 6-10 patients (for a total of 12 patients) receive treatment at that dose.

Patients are followed at 3 months.

PROJECTED ACCRUAL: A total of 54-84 patients (12-22 for stratum I, 18-28 for stratum II [closed to accrual as of 8/24/06] , and 24-34 for stratum III) will be accrued for this study within approximately 4.4 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor for which there is no known standard therapy that is potentially curative or capable of extending life expectancy

  • Unresectable disease
• Willing to provide biologic specimens to determine UGT1A1 genotype

• No CNS metastases

  • Prior CNS metastases allowed provided patient was treated with surgery and/or radiotherapy and is stable for more than 8 weeks

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.0 g/dL

Hepatic

• Bilirubin no greater than upper limit of normal (ULN) for patients with 6/6 UGT1A1 genotype (1.5 times ULN for patients with 6/7 [closed to accrual as of 8/24/06] or 7/7 UGT1A1 genotype)
• AST no greater than 3 times ULN (5 times ULN if there is liver involvement)

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No New York Heart Association class III or IV heart disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior allergy to platinum compounds, irinotecan, or to antiemetics or antidiarrheals appropriate for administration with study therapy
• No uncontrolled infection
• No seizure disorder
• No peripheral neuropathy grade 2 or greater

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 weeks since prior biologic therapy
• More than 4 weeks since prior immunotherapy
• No concurrent immunotherapy
• No concurrent prophylactic colony-stimulating factor therapy

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• More than 4 weeks since prior radiotherapy
• No prior radiotherapy to more than 25% of the bone marrow
• No concurrent radiotherapy

Surgery

• See Disease Characteristics

Other

• No other concurrent investigational therapy
• No concurrent sorivudine, brivudine, lamivudine, or stavudine
• No concurrent enrollment in any other study involving a pharmacologic agent for symptom control or therapeutic intent