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

• Status: Terminated
• Trial end date: 2006-11-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI); Schering-Plough
• Treatments: Fenretinide; Lonafarnib

Criteria

Inclusion Criteria:

• Patient has histologically proven squamous cell carcinoma of the head and neck which is biopsy accessible and is not considered curable by standard measures.

• Patient has a Karnofsky performance status >/= 70%

• Patient has adequate bone marrow function: *WBC >/= 3,000 cells/mm^3, *ANC >/= 1,500 cells/mm^3, *platelet count >/= 100,000 cells/mm^3, *Hgb >/= 9.0 g/dL.

• Patient has adequate liver function: *total bilirubin level>/= 2.5 g/dL.

• Transaminases (SGOT and/or SGPT) may be up to 2.5 x ULN if alkaline phosphatase isULN, or alkaline phosphatase may be up to 4 x ULN if transaminases are
• Patient has adequate renal function: a serum creatinine < 2 mg/dl

• Patient has signed a written informed consent.

• Patient has received no more than 2 prior chemotherapeutic regimens for recurrent or metastatic disease. Prior biologic therapy is not included.

Exclusion Criteria:

• Patient has received 3 or more prior chemotherapeutic regimens for recurrent/metastatic disease.

• No biopsy accessible tissue.

• Patient has received radiation therapy within the past 6 months.

• Prior radiation to the biopsy site.

• Patient has signs or symptoms of acute infection requiring systemic therapy.

• Patient exhibits confusion, disorientation, or has a history of major psychiatric illness which may impair patient's understanding of the informed consent.

• Patient has grade 3 or 4 neurotoxicity from previous anticancer treatment or significant neuropathy from any cause.

• Patient requires total parenteral nutrition with lipids.

• Surgery is anticipated to leave patient unable to swallow the SCH66336 or 4-HPR daily.

• Patient has a history of uncontrolled heart disease (including arrhythmia, angina, congestive heart failure, or any heart condition that cannot be controlled with regular ongoing medication)

• Because of the known teratogenic effect of retinoids, pregnant women and women who are currently breast-feeding may not participate in this study. All women of childbearing potential must have a negative pregnancy test within 24 hours prior to enrolling in the study.

• Serious infection or other intercurrent illness requiring immediate therapy.

• Inability to swallow oral medications, or other medical or social factors interfering with compliance.

• Patients may not take high dose synthetic or natural Vitamin A derivatives (>10,000 IU per day). Patients may not be taking high-dose vitamin A within 30 days of study entry.

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

• Patients with pre-existing retinopathy