Fenretinide and Lonafarnib in Treating Patients With Advanced or Recurrent Head and Neck Cancer

Head and Neck Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00103090
• Other study ID #: CDR0000411938
• Secondary ID: MDA-ID-01455NCI-
• Status: Terminated
• Phase: Phase 1
• First received: February 7, 2005
• Last updated: November 12, 2012
• Start date: January 2005
• Est. completion date: November 2006

Study information

• Verified date: November 2012
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs, such as fenretinide and lonafarnib, may stop the growth of head and neck cancer by blocking blood flow to the tumor. Fenretinide may also help tumor cells become normal cells. Lonafarnib may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving fenretinide together with lonafarnib may kill more tumor cells.

PURPOSE: This randomized phase I trial is studying the side effects and best dose of fenretinide and lonafarnib in treating patients with advanced or recurrent head and neck cancer.

Description:

OBJECTIVES:

Primary

• 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.

Secondary

• 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: November 2006
• Est. primary completion date: January 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the head and neck

• Advanced or recurrent disease

• Considered incurable by standard measures

• Tumor tissue accessible for biopsy

PATIENT CHARACTERISTICS:

Age

• Any age

Performance status

• stern Cooperative Oncology Group (ECOG) 0-1

Life expectancy

• Not specified

Hematopoietic

• White Blood Count (WBC) = 3,000/mm^3

• Absolute neutrophil count = 1,500/mm^3

• Platelet count = 100,000/mm^3

• Hemoglobin = 9.0 g/dL

Hepatic

• Bilirubin = 2.0 mg/dL

• Albumin = 2.5 g/dL

• Aspartate aminotransferase (AST or SGOT) and/or alanine aminotransferase (ALT or SGPT) = 2.5 times upper limit of normal (ULN) AND alkaline phosphatase normal OR

• Alkaline phosphatase = 4 times Upper Limit of Normal (ULN) AND Aspartate aminotransferase (AST or SGOT) and/or alanine aminotransferase (ALT or SGPT) normal

Renal

• Creatinine < 2 mg/dL

Cardiovascular

• No history of uncontrolled heart disease

• No arrhythmia

• No angina

• No congestive heart failure

• No other heart condition that cannot be controlled with regular ongoing medication

Gastrointestinal

• Able to swallow oral medication

• No requirement for total parenteral nutrition with lipids

Neurological

• No significant neuropathy

• No neurotoxicity = grade 3 from prior anticancer treatment

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective double-method contraception during and for at least 1 month after study participation

• No signs or symptoms of acute infection requiring systemic therapy

• No confusion, disorientation, or major psychiatric illness that would preclude giving informed consent

• No serious infection requiring immediate therapy

• No other illness requiring immediate therapy

• No pre-existing retinopathy

• No other medical or social factor that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Chemotherapy

Chemotherapy

• No more than 2 prior chemotherapeutic regimens for recurrent or metastatic disease

• Prior biologic therapy not considered a chemotherapeutic regimen

Endocrine therapy

• More than 2 days since prior and no concurrent high-dose chronic steroids

• More than 2 days since prior and no concurrent ethinylestradiol

• No concurrent anticancer hormonal therapy

Radiotherapy

• More than 6 months since prior radiotherapy

• No concurrent radiotherapy

Surgery

• No prior surgery that may affect the ability to swallow study drugs

Other

• More than 2 days since prior and no concurrent cytochrome P450 3A4 (CYP3A4) inducers or inhibitors, including any of the following:

• Gestodene

• Itraconazole

• Ketoconazole

• Cimetidine

• Erythromycin

• Carbamazepine

• Phenobarbital

• Phenytoin

• Rifampin

• Sulfinpyrazone

• Grapefruit juice

• More than 30 days since prior high-dose vitamin A

• No concurrent high-dose synthetic or natural vitamin A derivatives (> 10,000 IU/day)

• No concurrent antioxidants (e.g., vitamin E or vitamin C)

• No other concurrent investigational agents

• No other concurrent antineoplastic agents

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• Fenretinide
Oral 100 mg capsules in two divided doses at least 8 hours apart for 7 days each cycle.
• Lonafarnib
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.

Locations

Country	Name	City	State
United States	M.D. Anderson Cancer Center at University of Texas	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Modulation of intermediated biological endpoints at 6 weeks after treatment		6 weeks	No
Primary	Maximum tolerated dose (MTD)	MTD derived from lack of dose limiting toxicities (DLT) in 4 differing dose levels.	21 day course	Yes