Fenretinide in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

OBJECTIVES:

- Determine the response rate, time to progression, median survival, and percent of 1-year
survival in patients with recurrent or metastatic squamous cell carcinoma of the head
and neck treated with fenretinide.

- Determine the pharmacokinetics and safety of this drug in these patients.

OUTLINE: Patients receive oral fenretinide every 12 hours on days 1-7. Treatment repeats
every 3 weeks for at least 3 courses in the absence of disease progression or unacceptable
toxicity. Patients who achieve complete response continue treatment for 1 year.

PROJECTED ACCRUAL: A total of 16-35 patients will be accrued for this study.

Inclusion Criteria:

1. Biopsy-proven recurrent squamous cell carcinoma of the head and neck

2. Stage 4 disease, either at initial presentation or at recurrence. Patients with
metastatic disease at initial presentation must have received at least one prior
course of cytotoxic chemotherapy.

3. Patients who present with metastatic disease should have received no more than one
prior regimen of chemotherapy or biologic therapy to be eligible. Patients who
initially received adjuvant or induction chemotherapy and then recurred may have
received one additional cycle of chemotherapy or biologic therapy at the time of
recurrence. Patients may have received any number of cycles of a particular regimen of
chemotherapy.

4. Patients must have a life expectancy of at least 3 months

5. Biopsy of the recurrent lesion(s) is encouraged but not mandatory for enrollment.

6. Performance status grade 0-2.

7. Serum creatinine <= 1.5 mg/dL.

8. Serum transaminases and bilirubin <= 1.5 time normal.

9. Age >= 18 years.

10. White blood cell count >= 3,000; platelets >= 100,000; hemoglobin >= 9mg/dl.

11. Signed informed consent.

12. Women of childbearing potential must agree to utilize two methods of effective birth
control, one barrier, one hormonal, or should abstain from sexual intercourse that
could result in pregnancy. Contraceptive measures should be continued for at least one
month after fenretinide administration has been discontinued.

13. It is recommended that male patients with female partners of childbearing potential
use barrier contraception while on fenretinide.

Exclusion Criteria:

1. Pregnant women (women of childbearing potential must have a negative pregnancy test
within 24 hours prior to enrollment in the study); women who are currently
breast-feeding.

2. Grade 2 or greater peripheral neuropathy

3. Concurrent treatment with cytotoxic chemotherapy or radiation

4. Serious infection or other intercurrent illness requiring immediate therapy.

5. Inability to take oral medications, or other medical or social factors interfering
with compliance.

6. Patients on high dose synthetic or natural Vitamin A derivatives (>= 10,000 per day).

7. Patients should not take any anti-oxidants such as Vitamin C or E.