Combination Chemotherapy in Treating Patients With Advanced Solid Tumors

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

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.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: cisplatin; Drug: fenretinide; Drug: paclitaxel

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106-5065
      • Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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.

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: April 1, 2000
• Primary Completion (Actual): May 1, 2005
• Study Completion (Actual): August 1, 2006

Study Registration Dates

• First Submitted: June 2, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): June 11, 2010
• Last Update Submitted That Met QC Criteria: June 9, 2010
• Last Verified: June 1, 2010

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antineoplastic Agents, Phytogenic; Anticarcinogenic Agents; Paclitaxel; Fenretinide
• Other Study ID Numbers: CWRU3Y99; U01CA062502 (U.S. NIH Grant/Contract); P30CA043703 (U.S. NIH Grant/Contract); CWRU-3Y99 (Other Identifier: Case Comprehensive Cancer Center); NCI-T99-0098; CASE-3Y99 (Other Identifier: Case Comprehensive Cancer Center)