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
- 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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Modulation of intermediated biological endpoints at 6 weeks after treatment
Edward S. Kim
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|M.D. Anderson Cancer Center at University of Texas||Houston, Texas 77030|