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

This study has been terminated.
(Slow Accrual.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00103090
First received: February 7, 2005
Last updated: November 12, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Drug: Fenretinide
Drug: Lonafarnib
Phase 1

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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Modulation of intermediated biological endpoints at 6 weeks after treatment [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Maximum tolerated dose (MTD) [ Time Frame: 21 day course ] [ Designated as safety issue: Yes ]
    MTD derived from lack of dose limiting toxicities (DLT) in 4 differing dose levels.


Enrollment: 1
Study Start Date: January 2005
Study Completion Date: November 2006
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fenretinide + Lonafarnib
Lonafarnib daily for 21 days each cycle and with Fenretinide daily on days 1-7 only. On day 1 of cycle 1, Fenretinide only then beginning Lonafarnib on day 2 of cycle 1.
Drug: Fenretinide
Oral 100 mg capsules in two divided doses at least 8 hours apart for 7 days each cycle.
Other Name: 4-HPR
Drug: 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.
Other Names:
  • SCH66336
  • SCH 66336
  • Sarasar

Detailed 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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00103090

Locations
United States, Texas
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: Edward S. Kim M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00103090     History of Changes
Other Study ID Numbers: CDR0000411938, MDA-ID-01455, NCI-5709, SPRI-P03546, CDR0000411938, ID01-455
Study First Received: February 7, 2005
Last Updated: November 12, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
recurrent squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the larynx
stage III squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
recurrent squamous cell carcinoma of the lip and oral cavity
stage III squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
recurrent squamous cell carcinoma of the nasopharynx
stage III squamous cell carcinoma of the nasopharynx
stage IV squamous cell carcinoma of the nasopharynx
recurrent squamous cell carcinoma of the oropharynx
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity
stage III squamous cell carcinoma of the paranasal sinus and nasal cavity
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
recurrent salivary gland cancer
salivary gland squamous cell carcinoma
stage III salivary gland cancer
stage IV salivary gland cancer
recurrent metastatic squamous neck cancer with occult primary
metastatic squamous neck cancer with occult primary squamous cell carcinoma

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms

ClinicalTrials.gov processed this record on October 19, 2014