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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


Phase 1
N/A
N/A
Not Enrolling
Both
Head and Neck Cancer

Thank you

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Modulation of intermediated biological endpoints at 6 weeks after treatment

Outcome Time Frame:

6 weeks

Safety Issue:

No

Principal Investigator

Edward S. Kim

Investigator Role:

Study Chair

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000411938

NCT ID:

NCT00103090

Start Date:

January 2005

Completion Date:

November 2006

Related Keywords:

  • Head and Neck Cancer
  • 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
  • Head and Neck Neoplasms

Name

Location

M.D. Anderson Cancer Center at University of TexasHouston, Texas  77030