Capecitabine, Irinotecan, and Oxaliplatin in Treating Patients With Metastatic Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as capecitabine, irinotecan, and oxaliplatin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of capecitabine when given together with irinotecan and oxaliplatin in treating patients with metastatic cancer.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose and dose-limiting toxicities of capecitabine. Secondary Determine the recommended phase II dose of capecitabine. Define the toxicity profile. Evaluate potential antitumor activity in terms of objective response, duration of response, and time to disease progression. Evaluate the pharmacokinetic profile of capecitabine and irinotecan hydrochloride. OUTLINE: This is a dose-escalation study of capecitabine conducted in two parts. Part I: Patients receive irinotecan hydrochloride IV over 90 minutes on day 1 and oral capecitabine twice daily on days 1-7. Treatment repeats every 2 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity. Cohorts of up to 6 patients receive escalating doses (up to 5 dosages) of capecitabine. The maximum tolerated dose (MTD) is defined as the dose at which 50% of patients experience toxicity during the first 2 courses of therapy. Part II: Patients receive oxaliplatin IV over 2 hours and irinotecan hydrochloride IV over 90 minutes on day 1 and oral capecitabine on days 1-7. Treatment repeats every 2 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity. Cohorts of up to 6 patients receive escalating doses (up to 7 dosages) of capecitabine. The MTD is defined as in part I.

Official Title
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Phase I Study Evaluating the Feasibility of Chemotherapy With Capecitabine, Irinotecan, and Oxaliplatin in Patients With Metastatic Carcinoma

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Inclusion criteria: Histologically confirmed metastatic carcinoma Primary tumor may be present No curative therapy available or the patient achieved no response to prior standard therapy Nonresectable metastatic disease Measurable, evaluable, or nonevaluable disease Exclusion criteria: Symptomatic brain metastases or carcinomatous meningitis PATIENT CHARACTERISTICS: Inclusion criteria: WHO performance status 0-2 Life expectancy ≥ 12 weeks ANC ≥ 2,000/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10 g/dL Bilirubin < 1.25 times upper limit of normal (ULN) (1.5 times ULN if due to liver metastases) Transaminases < 3 times ULN (5 times ULN if due to liver metastases) Alkaline phosphatase ≤ 3 times ULN Creatinine ≤ 1.5 times ULN Creatinine clearance > 30 mL/min Not pregnant or nursing Fertile patients must use effective contraception Exclusion criteria: Severe concurrent infection or major organ failure, including any of the following: Cardiac disease Diabetic decompensation Clinically active infection Prior severe toxicity from fluorouracil Intestinal obstruction or subobstruction Malabsorption syndrome Peripheral neuropathy Uncontrolled epilepsy PRIOR CONCURRENT THERAPY: Inclusion criteria: At least 4-6 weeks since prior anticancer chemotherapy Exclusions criteria: Prior chemotherapy with any of the study drugs Prior major intestinal resection Concurrent participation in another clinical study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Non-Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: irinotecan hydrochloride|nan|
|Drug: oxaliplatin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of capecitabine |  |  | 
| Dose-limiting toxicities |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended phase II dose of capecitabine |  |  | 
| Toxicity profile |  |  | 
| Objective response |  |  | 
| Duration of response |  |  | 
| Time to disease progression |  |  | 
| Pharmacokinetic profile of capecitabine and irinotecan hydrochloride |  |  | 

 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