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

Alternate Title

Isotretinoin Compared With Placebo in Preventing Second Primary Cancers in Patients Treated for Stage I or Stage II Head and Neck Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Prevention	Completed	over 18	NCI	EST-C-0590 MAYO-887451, NCCTG-887451, NCI-P92-0026

Objectives

I.  Determine, in a phase III setting, the efficacy of isotretinoin (13-CRA) 
in preventing dysplastic changes and second malignancies in patients with 
squamous cell carcinoma of the head and neck region who have a high 
probability of cure from their primary cancer.

II.  Compare the time to diagnosis of a second primary and survival between 
patients treated with 13-CRA vs. placebo.

III.  Determine the cost-benefit ratio for 13-CRA by assessing the toxic 
effects experienced in patients treated with 13-CRA vs. those treated with 
placebo.

Entry Criteria

Disease Characteristics:

Histologically confirmed squamous cell carcinoma of the head and neck rendered
disease-free following primary surgery and/or radiotherapy

The following AJCC sites and stages are eligible:
  Oral cavity, oropharynx, and larynx:  T1-2, N0, M0
  Hypopharynx:  T1, N0, M0

Wide surgical excision with negative margins required
  Radical or modified radical neck dissection or primary radiotherapy required
  of some lesions (see protocol for details)

Chest and cervical spine x-rays required within 30 days following primary
therapy

Prior/Concurrent Therapy:

Biologic therapy:
  No prior biologic therapy

Chemotherapy:
  No prior chemotherapy

Endocrine therapy:
  No prior endocrine therapy

Radiotherapy:
  Radiotherapy completed within 2 years prior to randomization
  External-beam radiotherapy or brachytherapy allowed

Surgery:
  Surgical resection completed within 2 years prior to randomization

Patient Characteristics:

Age:
  Over 18

Performance status:
  ECOG 0 or 1

Hematopoietic:
  (within 2 weeks prior to randomization)
  WBC at least 3,500
  Platelets at least 125,000

Hepatic:
  (within 2 weeks prior to randomization)
  Bilirubin less than 2.0 mg/dL
  AST less than 2 times normal
  Alkaline phosphatase less than 2 times normal
  Fasting triglycerides less than 210 mg/dL
  Fasting cholesterol less than 350 mg/dL
  No systemic therapy for hyperlipidemia

Renal:
  (within 2 weeks prior to randomization)
  Creatinine less than 2.5 mg/dL

Cardiovascular:
  No severe (NYHA class III/IV) or symptomatic CAD
  No history of coronary artery bypass surgery

Other:
  No fertile women
  No prior, synchronous, or concurrent malignancy except basal cell skin
     cancer

Expected Enrollment

Between 75 and 200 patients will be entered annually.  Accrual will be stopped 
in the third, fourth, or fifth year if efficacy is highly significant (0.5% 
level).

Outline

Randomized, double-blind study.

Arm I:  Chemoprevention.  Isotretinoin, 13-CRA, NSC-329481.

Arm II:  Control.  Placebo, PLCB.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Harlan Pinto, MD, Protocol chair		Ph: 650-725-9057

North Central Cancer Treatment Group

Charles Loprinzi, MD, Protocol chair		Ph: 507-284-8964 Email: cloprinzi@mayo.edu

Mayo Clinic Cancer Center

Charles Loprinzi, MD, Protocol chair		Ph: 507-284-8964 Email: cloprinzi@mayo.edu