Combination Chemotherapy in Treating Patients With Solid Tumors

The Ohio State University

Status and phase: Unknown; Phase 1

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00009932

CDR0000068425 (Registry Identifier)

OSU-00H0186

NCI-2530

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: Phase I trial to study the effectiveness of combining fenretinide, paclitaxel, and cisplatin in treating patients who have solid tumors that have not responded to previous therapy.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose, clinical toxicity, and recommended phase II dose of fenretinide when combined with paclitaxel and cisplatin in patients with refractory solid tumors.
• Determine the pharmacokinetics of this regimen in these patients.
• Determine the therapeutic response to this regimen in these patients.

OUTLINE: This is a dose escalation, multicenter study of fenretinide.

Patients receive oral fenretinide twice daily on days 1-7 and paclitaxel IV over 3 hours followed by cisplatin IV over 2 hours on day 2. On day 8 of course 1, patients also receive fenretinide once in the morning. Treatment repeats every 3 weeks for a maximum of 8 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response receive 2 additional courses.

Cohorts of 3-6 patients receive escalating doses of fenretinide 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: A total of 3-24 patients will be accrued for this study within 1 year.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically proven refractory solid tumor for which paclitaxel and cisplatin are reasonable therapeutic options

• No active CNS disease

  • CNS metastasis allowed if measurable disease outside of the CNS and patient completed and recovered from 1 prior course of CNS radiotherapy (if clinically indicated)

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2 OR
• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Platelet count at least 100,000/mm3
• Absolute neutrophil count at least 1,500/mm3

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• ALT and AST no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if related to liver metastases)

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No severe symptomatic cardiac disease

Other:

• No clinically significant/evident retinopathy
• No other malignancy within the past 5 years except localized nonmelanoma skin cancer or carcinoma in situ of the cervix
• No uncontrolled infection
• No other significant medical or psychiatric condition that would increase risk
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception for 1 month before, during, and for at least 2 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• No prior paclitaxel, cisplatin, or fenretinide
• At least 4 weeks since other prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy to only site of measurable/evaluable disease
• No prior radiotherapy to more than 25% of bone marrow

Surgery:

• At least 2 weeks since prior therapeutic surgery and recovered

Other:

• At least 4 weeks since prior routine vitamin A of at least 10,000 IU/ day or beta carotene of at least 10 mg/day