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: This phase I trial is studying the side effects and best dose of combination chemotherapy in treating patients with advanced solid tumors.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of the combination of fenretinide, paclitaxel, and cisplatin in patients with advanced solid tumors. Determine the effect of fenretinide on the pharmacokinetics of paclitaxel and cisplatin. Assess the relationship between dose or plasma levels of fenretinide and the safety and antitumor effects, in terms of overall response, response rate, and progression-free survival rate, in these patients. OUTLINE: This is a dose-escalation study of paclitaxel and cisplatin. Patients receive oral fenretinide twice daily for 7 days. Patients receive paclitaxel IV over 3 hours and cisplatin IV over 30 minutes on day 7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of paclitaxel and cisplatin 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, additional patients are accrued to receive paclitaxel and cisplatin at the recommended phase II dose. PROJECTED ACCRUAL: Approximately 15-24 patients will be accrued for this study within 12-24 months.

Official Title
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A Phase I Trial of Fenretinide in Combination With Paclitaxel and Cisplatin

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: cisplatin
* Drug: fenretinide
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed advanced solid tumor not amenable to conventional surgery, radiotherapy, or chemotherapy No brain metastases or primary brain tumors PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: At least 12 weeks Hematopoietic: WBC at least 3,500/mm^3 Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin greater than 9.0 g/dL Hepatic: Bilirubin less than 1.6 mg/dL AST and ALT less than 2 times upper limit of normal PT and PTT normal OR INR less than 1.1 Renal: Creatinine less than 1.5 mg/dL OR 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 No extensive signs of macular degeneration, including exudative or atrophic macular lesions reducing corrected vision to less than 20/40 PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics At least 3 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered Prior platinum-containing agents and taxane exposure allowed with no evidence of neurotoxicity Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics At least 4 weeks since prior radiotherapy and recovered Surgery: Not specified Other: No concurrent vitamin A supplements No concurrent supplemental antioxidants

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: cisplatin|Patients receive cisplatin IV over 30 minutes on day 7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.Cohorts of 3-6 patients receive escalating doses of paclitaxel and cisplatin until the maximum tolerated dose (MTD) is determined.|
|Drug: fenretinide|Patients receive oral fenretinide twice daily for 7 days. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.|
|Drug: paclitaxel|Patients receive paclitaxel IV over 3 hours. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.Cohorts of 3-6 patients receive escalating doses of paclitaxel and cisplatin until the maximum tolerated dose (MTD) is determined.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohorts of 3-6 patients receive escalating doses of paclitaxel and cisplatin until the maximum tolerated dose (MTD) is determined. |  | Courses (7 days) repeat every 21 days 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