Combination Chemotherapy in Treating Patients With Advanced Solid Tumors

Case Comprehensive Cancer Center (Case CCC)

Status and phase: Completed; Phase 1

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Treatments: Drug: paclitaxel; Drug: fenretinide; Drug: cisplatin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00005819

U01CA062502 (U.S. NIH Grant/Contract)

CWRU3Y99

CWRU-3Y99 (Other Identifier)

P30CA043703 (U.S. NIH Grant/Contract)

NCI-T99-0098

CASE-3Y99 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 21 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)