RATIONALE: Drugs used in chemotherapy, such as irinotecan, oxaliplatin, and capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining irinotecan, oxaliplatin, and capecitabine in treating patients who have unresectable solid tumors.

Condition	Treatment or Intervention	Phase
unspecified adult solid tumor, protocol specific	Drug: capecitabine  Drug: irinotecan  Drug: oxaliplatin  Procedure: chemotherapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of irinotecan, oxaliplatin, and capecitabine in patients with unresectable solid tumors with or without the UGT1A1*28 genotype.
• 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 assigned to 1 of 2 groups according to UGT1A1*28 genotype.

• 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 receive irinotecan, oxaliplatin, and capecitabine at the MTD as in group I. Cohorts of 3-6 patients receive escalating doses of irinotecan (beginning at the MTD determined in group I) until the MTD is determined. The MTD is defined as in group I. 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 24-86 patients (12-46 for group I and 12-40 for group II) will be accrued for this study within approximately 6-23 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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*28 polymorphism status*
• No CNS metastases
• Prior CNS metastases allowed provided patient was treated with surgery and/or radiotherapy and is stable for more than 8 weeks NOTE: *Only for patients involved in determining the maximum tolerated dose

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 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

Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting

Study chairs or principal investigators

Mathew P. Goetz, MD,  Study Chair,  Mayo Clinic Cancer Center   
Matthew M. Ames, PhD,  Mayo Clinic Cancer Center   

Study ID Numbers:  CDR0000344367; MAYO-MC0311; NCI-6240; NCT00074321
Record last reviewed:  December 2004
Last Updated:  February 7, 2005
Record first received:  December 10, 2003
ClinicalTrials.gov Identifier:  NCT00074321
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08