Fenretinide and Lonafarnib in Treating Patients With Advanced or Recurrent Head and Neck Cancer
RATIONALE: Drugs, such as fenretinide and lonafarnib, may stop the growth of head and neck cancer by blocking blood flow to the tumor. Fenretinide may also help tumor cells become normal cells. Lonafarnib may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving fenretinide together with lonafarnib may kill more tumor cells.
PURPOSE: This randomized phase I trial is studying the side effects and best dose of fenretinide and lonafarnib in treating patients with advanced or recurrent head and neck cancer.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase IB Randomized Translational Study of Fenretinide (4-HPR) in Combination With SCH66336, a Farnesyl Transferase Inhibitor, in Patients With Advanced or Recurrent Head and Neck Cancer|
- Modulation of intermediated biological endpoints at 6 weeks after treatment [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
- Maximum tolerated dose (MTD) [ Time Frame: 21 day course ] [ Designated as safety issue: Yes ]MTD derived from lack of dose limiting toxicities (DLT) in 4 differing dose levels.
|Study Start Date:||January 2005|
|Study Completion Date:||November 2006|
|Primary Completion Date:||January 2006 (Final data collection date for primary outcome measure)|
Experimental: Fenretinide + Lonafarnib
Lonafarnib daily for 21 days each cycle and with Fenretinide daily on days 1-7 only. On day 1 of cycle 1, Fenretinide only then beginning Lonafarnib on day 2 of cycle 1.
Oral 100 mg capsules in two divided doses at least 8 hours apart for 7 days each cycle.
Other Name: 4-HPRDrug: Lonafarnib
Oral capsules with 50 mg, 75 mg, or 100 mg formulation in two divided doses at least 8 hours apart for 21 days each cycle.
- Determine the biological activity and tolerability of fenretinide and lonafarnib in patients with advanced or recurrent squamous cell carcinoma of the head and neck.
- Determine the toxicity profile of this regimen in these patients.
- Determine the maximum tolerated dose of this regimen in these patients.
- Determine the dose-limiting toxicity of this regimen in these patients.
- Determine a recommended phase II dose of this regimen in these patients.
OUTLINE: This is a dose-escalation study followed by a randomized study.
- Dose-escalation portion: Patients receive oral fenretinide twice daily on days 1-7 and oral lonafarnib twice daily on days 1*-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of fenretinide and lonafarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
- Randomized portion: After the dose-escalation portion of this study is completed, additional patients (including patients who participate in the dose-escalation portion of this study) are accrued and randomized to 1 of 4 dose levels. All patients receive fenretinide and lonafarnib as in the dose-escalation portion of this study.
NOTE: *Lonafarnib is not administered on day 1 of course 1.
After completion of study treatment, patients are followed every 3 months for 2 years.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00103090
|United States, Texas|
|M.D. Anderson Cancer Center at University of Texas|
|Houston, Texas, United States, 77030-4009|
|Study Chair:||Edward S. Kim||M.D. Anderson Cancer Center|