Neoplasms

All Conditions

Symptoms and General Pathology

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Fenretinide

Lonafarnib

Protective Agents

Enzyme Inhibitors

SCH66336 daily for 21 days each cycle and with 4-HPR daily on days 1-7 only. On day 1 of cycle 1, 4-HPR only beginning SCH66336 on day 2 of cycle 1.

Oral 100 mg capsules in two divided doses at least 8 hours apart for 7 days each cycle.

Fenretinide (4-HPR)

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.

SCH66336

Edward S Kim, MD

The primary objective of this study is to estimate the modulation of intermediate biological endpoints of the combination of 4-HPR and SCH66336, a farnesyl transferase inhibitor (FTI), across 4 randomly assigned dose levels in patients with locally advanced or recurrent head and neck cancer. We will also assess the activity, safety, tolerability and side effects of 4-HPR/SCH66336 and hope to establish a phase II regimen.

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.

4-HPR and FTI in Head and Neck Squamous Cell Carcinoma (HNSCC)

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

MTD derived from lack of dose limiting toxicities (DLT) in 4 differing dose levels.

National Cancer Institute (NCI)

Schering-Plough

M.D. Anderson Cancer Center

Nervous System Diseases

Rare Diseases

Glioma

Glioblastoma

Brain Neoplasms

Astrocytoma

Oligodendroglioma

Gliosarcoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Oligoastrocytoma

Anaplastic Oligoastrocytoma

Neuroepithelioma

Channel Blockers

Anticonvulsants

Analgesics

Central Nervous System Depressants

Psychotropic Drugs

Central Nervous System Stimulants

Temozolomide

Phenytoin

Carbamazepine

Phenobarbital

Oxcarbazepine

Convulsants

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients receiving enzyme-inducing anti-epileptic drugs (EIAEDs)such as carbamazepine, phenobarbitol, phenytoin, phosphenytoin, oxcarbamazepine, primadone)

Patients on non CYP3A4-inducing anti-convulsants or patients not on any anti-convulsants.

2 separate strata accrued independently: Stratum 1-pts receiving CYP3A4-inducing anticonvulsants. Stratum 2-pts on non CYP3A4-inducing anticonvulsants or pts not on any anti-convulsants. Each strata treated \& escalated independent of each other. Temozolomide administered orally at dose of 150 mg/m2 daily for 5 days, at bedtime, for 1st cycle \& escalated to 200 mg/m2 daily for 5 days, at bedtime during subsequent cycles if tolerated. Treatment cycles repeated every 4wks following doses of Temozolomide from previous cycle. SCH 66336 administered orally twice daily, approximately every 12hrs. Except as specifically noted, pts advised to take capsules wh morning \& evening meals, with approximately 240ml of non-carbonated water. Initial doses will be 125mg BID for stratum 1 \& 75mg BID for stratum2. Treatment cycles repeated every 4 wks following dose of Temozolomide from previous cycle.

Temodar and SCH 66336

Annick Desjardins, MD

Objectives:

To determine maximum tolerated dose of farnesyl transferase inhibitor, SCH 66336, when administered w TEMODAR®.

To characterize any toxicity associated w combo of farnesyl transferase inhibitor, SCH 66336, \& TEMODAR®.

To observe patients for clinical antitumor response when treated with combination of farnesyl transferase inhibitor, SCH 66336, \& TEMODAR®.

To assess pharmacokinetics of SCH 66336 for patients on \& not on enzyme inducing antiepileptic drugs.

2 separate strata accrued independently of each other: Stratum1-Patients receiving Dilantin, Tegretol / phenobarbital. Stratum2-Patients on anti-convulsants other than Dilantin, Tegretol / phenobarbital / Patients not on any anti-convulsants. Each stratum treated \& escalated independent of each other. Temozolomide administered orally at dose of 150mg/m2 daily for 5 days, at bedtime, for 1st cycle \& escalated to 200mg/m2 daily for 5 days, at bedtime during subsequent cycles if tolerated. Treatment cycles may be repeated every 4 weeks following doses of Temozolomide from previous cycle. SCH 66336 administered orally twice day, approximately every 12hrs. Initial doses will be 125mg BID for stratum 1 \& 75mg for stratum 2. Treatment cycles may be repeated every 4 weeks following dose of Temozolomide from previous cycle.

Subjects are patients with malignant glioma histologically confirmed at diagnosis, who were treated previously with conventional external beam radiation (XRT) \& with or without chemo, \& have stable disease, recurrence/relapse at time of enrollment. Approximately 48 subjects will be enrolled.

Temozolomide has been well tolerated by both adults \& children with most common toxicity being mild myelosuppression. Other, less likely, potential toxicities include nausea \& vomiting, constipation, headache, alopecia, rash, burning sensation of skin, esophagitis, pain, diarrhea, lethargy, \& hepatotoxicity. Hypersensitivity reactions have not yet been noted with Temozolomide. As is case with many anti-cancer drugs, Temozolomide may be carcinogenic. Rats given Temozolomide have developed breast cancer. Significance of this finding for humans is not presently known.

Significant adverse events observed for SCH66336 have included vomiting, diarrhea, anorexia, headaches, reversible renal toxicities, \& hematological toxicities. SCH 66336, although not genotoxic, inhibits rapidly proliferating cells \& at high doses inhibits spermatogenesis in male rats. It is not clear that inhibition of spermatogenesis is reversible,\& patients should be advised of possibility of irreversible sterility.

PH I Addition of Farnesyl Transferase Inhibitor to Temozolomide for Pts w Gr 3 & 4 Malignant Gliomas

A Phase I Trial of the Addition of the Farnesyl Transferase Inhibitor, SCH 66336, to Temodar for Patients With Grade 3 and 4 Malignant Gliomas

Duke University

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
4-HPR and FTI in Head and Neck Squamous Cell Carcinoma (HNSCC)	NCT00102635	Head and Neck C...	Fenretinide (4-... SCH66336	-	M.D. Anderson Cancer Center
PH I Addition of Farnesyl Transferase Inhibitor to Temozolomide for Pts w Gr 3 & 4 Malignant Gliomas	NCT00612651	Gliosarcoma Glioblastoma Anaplastic Astr...	Temodar and SCH...	18 Years -	Duke University

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