Trial Information

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

The drug fenretinide is a retinoid that is similar to vitamin A. It is believed that
fenretinide can cause cancer cells to die. SCH66336 is a drug that blocks farnesyl protein
transferase (a substance needed by cancer cells to grow). It is believed that SCH66336 may
selectively stop cancer cells from growing while not affecting normal cells.

Both SCH66336 and fenretinide are taken orally and must be swallowed whole (i.e., the drugs
may not be broken to make swallowing easier). Individuals who cannot take the study
medications whole by mouth cannot enroll in this study.

In this study participants will receive SCH66336 twice a day for each day of a 21-day cycle.
Participants will also take fenretinide twice a day on Days 1-7 of the same cycle. Before
beginning treatment, participants will have a complete physical exam, including measurement
of height, weight, and vital signs. Participants will have blood and urine tests, a chest
x-ray, and an ECG (heart function test). Females who are able to become pregnant must have
a negative blood pregnancy test. In addition, all participants will have a neurological
exam and will complete a questionnaire about their night vision. Some individuals may need
an eye exam.

Before beginning treatment, participants will have a biopsy of their tumor and will provide
a sample of their buccal mucosa (inner cheek). In the biopsy, a sample of tumor tissue will
be removed with a large needle. The buccal mucosa sample will be obtained by scraping the
inside of the cheek. Participants will also have an extra blood sample (about 2
tablespoons) drawn. The tumor, buccal mucosa, and blood samples are all being obtained for
research purposes only and will not directly benefit the participant.

During the study, a physician will examine participants at least once a week for the first
cycle of treatment. A treatment cycle is 3 weeks. Participants will also have weekly blood
tests. After the first cycle of treatment, participants will have exams every 3 weeks. In
addition, participants will have urine tests every 3 weeks, a neurological exam after the
first 3 weeks and then as needed, and a chest x-ray every 3 weeks. Every 3 months,
participants will complete a questionnaire about their night vision and will have an eye
exam, if needed.

While on this study, individuals will also participate in a pharmacokinetic study to measure
the levels of the drugs in the blood. On the first day of treatment, the participant will
have blood samples (about 1 teaspoon each) drawn before taking fenretinide and then 1, 2, 4,
6, 9, and 12 hours after taking fenretinide. The participant will not take the first dose
of SCH66336 until after these blood samples have been taken. Additional blood samples
(about 1 teaspoon each) will be taken at these same times on Day 7 of the first treatment
cycle and on Day 1 of the second treatment cycle. A single blood sample (about 1 teaspoon)
will be taken before taking the study drugs on Day 7 of treatment Cycles 3, 4, 5, and 6.

Participants will have biopsies of their tumors, extra blood tests and will provide buccal
mucosa samples on Days 7 and 21 of the first treatment cycle. These biopsies, cheek
scrapings, and extra blood tests are for research purposes only and will not directly
benefit the participant. Approximately two tablespoons of blood will be drawn during each
of these extra blood tests. This blood, buccal mucosa (cheek), and tumor tissue will be
studied to learn how the treatment drugs work in the body and what effects they have.
Participants may remain on the study as long as they are responding to the
SCH66336/fenretinide combination and as long as their physician feels it is of benefit.

After completing treatment, participants will be contacted about every 3 months to check on
the disease status. Participants will come to M.D. Anderson for clinical evaluations every
3 months for a period of 24 months.

Fenretinide is in the form of capsules and SCH66336 is in the form of tablets. Participants
will take the fenretinide capsules by mouth twice a day for seven days in a row at the start
of each treatment cycle. Participants will take the SCH66336 tablets twice a day for 21
days in a row in each cycle. Participants will be given a "pill diary" in which they should
record when they take the study medications and how many capsules and tablets they take.
Participants will bring this diary and any unused medication when they return to the clinic
for their check-ups. At the beginning of a treatment cycle, participants should take both
drugs together at least 8 hours apart with either a high-fat meal or a glass of whole milk.
Participants should continue taking the SCH66336 tablets at least 8 hours apart and with a
meal or a glass of whole milk during Days 8-21 of each treatment cycle. Participants will
not take fenretinide capsules during Days 8-21 of a treatment cycle.

While on this study, participants may not drink grapefruit juice.

This is an investigational study. The FDA has authorized the use of this drug combination
in research but has not approved it for widespread use. About 40 individuals will take part
in this study. All will be enrolled at M.D. Anderson Cancer Center.