Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Prevention	Closed	over 18		NCOG-CC7H871J RTOG-8910, NCI-C88-0001

Objectives

I.  Determine, in a Phase III setting, the efficacy of isotretinoin in 
preventing dysplastic changes and second malignancies in patients with 
squamous cell carcinoma of the head and neck who have a high probability of 
cure from their primary cancer.
II.  Compare the time to diagnosis of a second primary and survival time 
between patients treated with isotretinoin and those treated with a placebo.
III.  Determine the cost-benefit ratio for isotretinoin by assessing the 
toxicities experienced in patients treated with isotretinoin vs. those treated 
with placebo.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Patients over 18 years of age with 
histologically confirmed squamous cell carcinoma of the head and neck region 
who have been rendered disease-free following primary surgery and/or 
radiotherapy.  AJCC stages T1-2 N0 of the oral cavity, oropharnynx, larynx, 
nasopharynx, and paranasal sinus and T1 N0 of the hypopharynx are eligible; 
distant metastases exclude.  The extent of surgical resection will have been 
dictated by the extent of tumor at the time of initial evaluation; the primary 
lesion must have been widely excised using accepted criteria for adequate 
excision depending on the region involved, and the margins must have been 
negative.  Patients who were to undergo neck dissection may have had a radical 
or a modified radical dissection, at the discretion of the surgeon.  
Radiotherapy may have consisted of either external beam irradiation and/or 
brachytherapy, as specified in the protocol.  Any other prior therapy renders 
the patient ineligible.  Patients must be randomized within 35 days of 
completion of treatment of the primary.  Women of childbearing potential are 
excluded.  A Karnofsky performance status of 60 or better is required, as are 
the following laboratory parameters indicating adequate hematologic, hepatic, 
and renal function:  WBC at least 3,500 and platelets at least 125,000; 
bilirubin less than 2 mg/dl, serum SGOT and alkaline phosphatase each less 
than twice normal, fasting serum triglyceride less than 210 mg/dl, and fasting 
cholesterol less than 350 mg/dl; and serum creatinine less than 2.5 mg/dl.  
All chest x-rays and scans must have been done within 35 days after definitive 
treatment prior to randomization and all hematology and chemistries within 2 
weeks prior to randomization.  The following conditions exclude:  current 
systemic therapy for hyperlipidemia, symptomatic arteriosclerotic coronary 
artery disease or a New York Heart Association classification III-IV, prior 
coronary bypass surgery, and prior or concurrent malignancy other than basal 
cell skin cancer.

Expected Enrollment

It is estimated that 125-210 patients will be entered annually.  Accrual will 
be stopped in the third, fourth, or fifth year if efficacy is highly 
significant (0.5% level) or at any time for unexpected toxicity or any other 
serious contingency.

Outline

Randomized double-blind study.  Patients must be randomized within 35 days of 
definitive surgery and/or radiotherapy.
Arm I:  Single-agent Chemoprevention.  13-cis-Retinoic Acid, Isotretinoin, 
13-cRA, NSC-329481.
Arm II:  Control.  Placebo.

Trial Contact Information

Trial Lead Organizations

Clinical Research Program - Northern California Cancer Center

Charlotte Jacobs, MD, Protocol chair		Ph: 650-725-8738; 800-756-9000 Email: cjacobs@stanford.edu

Radiation Therapy Oncology Group

Philip Rubin, MD, Protocol chair		Ph: 716-275-2229 Email: lkoprowski@radonc.medinfo.rochester.edu