Combination Chemotherapy in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy in treating patients who have advanced solid tumors.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose and dose-limiting toxicity of irinotecan and capecitabine when given in combination with a fixed dose of oxaliplatin in patients with advanced solid tumors. Determine the pharmacokinetic parameters of this regimen in these patients. Determine the antitumor response of these patients treated with this regimen. OUTLINE: This is a dose-escalation study of irinotecan and capecitabine. Patients receive oxaliplatin IV over 2 hours followed 1 hour later by irinotecan IV over 30 minutes once weekly for 4 weeks. Patients also receive oral capecitabine twice daily on days 1-5 weekly for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of irinotecan 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. PROJECTED ACCRUAL: Approximately 9-15 patients will be accrued for this study within 9-15 months.

Official Title
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Phase I Study of Oxaliplatin (NSC# 266046), Irinotecan, and Capecitabine in Patients With Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: capecitabine
* Drug: irinotecan hydrochloride
* Drug: oxaliplatin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of solid tumor not amenable to curative surgery, radiotherapy, or chemotherapy Bidimensionally measurable or evaluable disease No brain metastases or primary brain tumors PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 12 weeks Hematopoietic: WBC at least 4,000/mm^3 Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin greater than 10.0 g/dL Hepatic: Bilirubin no greater than 1.5 mg/dL AST and ALT less than 2 times normal Renal: Creatinine no greater than 1.5 mg/dL Creatinine clearance greater than 60 mL/min 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 during and for 6 months after study No known hypersensitivity to fluorouracil PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics At least 3 weeks since prior chemotherapy (6 weeks for mitomycin and carmustine) and recovered Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics At least 4 weeks since prior large-field radiotherapy and recovered Surgery: Not specified

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: capecitabine|Patients receive oral capecitabine twice daily on days 1-5 weekly for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of irinotecan and capecitabine until the maximum tolerated dose(MTD).|
|Drug: irinotecan hydrochloride|Patients receive irinotecan IV over 30 minutes once weekly for 4 weeks (one hour after oxaliplatin). Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of irinotecan and capecitabine until the maximum tolerated dose(MTD).|
|Drug: oxaliplatin|Patients receive oxaliplatin IV over 2 hours. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximum tolerated dose and dose-limiting toxicity of irinotecan and capecitabine when given in combination with a fixed dose of oxaliplatin in patients with advanced solid tumors. |  | Treatment cycle is four weeks, repeated every six weeks in the absence of disease progression or unacceptable toxicity. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific