RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of tretinoin and/or fenretinide may be an effective way to prevent the recurrence or further development of dysplastic nevus syndrome.

PURPOSE: Randomized phase II trial to compare the effectiveness of tretinoin with or without fenretinide in treating patients with dysplastic nevus syndrome.

Condition	Treatment or Intervention	Phase
stage I melanoma stage II melanoma prevention of skin cancer	Drug: fenretinide  Drug: tretinoin	Phase II

Further Study Details: 

OBJECTIVES: I. Compare the efficacy (clinical and histologic evidence of regression) of topical tretinoin with or without systemic fenretinide in patients with dysplastic nevi with personal or family history of cutaneous melanoma.

PROTOCOL OUTLINE: This is a randomized, double blind study. Patients are stratified by personal history of cutaneous melanoma vs family history of cutaneous melanoma in at least 2 blood relatives vs both personal history of melanoma and family history of cutaneous melanoma in at least 2 blood relatives.

Patients are randomized to receive either topical tretinoin twice daily and oral fenretinide once a day for 12 months (arm I) or topical tretinoin twice daily and oral placebo once a day for 12 months (arm II). Tretinoin is applied to one half of the back with the untreated side of the back serving as a matched control.

Patients are followed every 3 months until year 2, every 6 months for years 2-5, and then annually thereafter.

PROJECTED ACCRUAL: There will be 78 patients accrued into this study over 1.5-2.3 years.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Clinically dysplastic nevi with a personal history of cutaneous melanoma and/or a family history of cutaneous melanoma in two or more blood relatives (blood relatives include first, second, or third degree relatives from the same blood line)
• Clinically dysplastic nevi defined as: At least 5 mm in diameter and flatness (either a component or throughout) with at least 1 of the following: Variable pigmentation; Irregular or asymmetrical outline; Indistinct border
• Must have at least 6 large (diameter at least 5 mm) clinically dysplastic nevi on each side of the back
• No stage III or IV melanoma; Patients with history of melanoma who received adjuvant therapy must be greater than 1 year from completion of therapy

--Prior/Concurrent Therapy--

• See Disease Characteristics
• Biologic therapy: Not specified
• Chemotherapy: Not specified
• Endocrine therapy: Not specified
• Radiotherapy: Not specified
• Surgery: No prior coronary bypass surgery
• Other: No prior systemic retinoids; At least 2 weeks since other mineral, herbal, or vitamin supplements except for patients who have been taking supplements prior to study and agree to continue the same supplement(s), on the same schedule for the entire duration of study; No concurrent systemic therapy for hyperlipidemia

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2
• Life expectancy: Not specified
• Hematopoietic: WBC greater than 3,500/mm3; Platelet count greater than 100,000/mm3
• Hepatic: Bilirubin less than 2.0 mg/dL; AST less than 2 times normal; Alkaline phosphatase less than 2 times normal
• Renal: Creatinine less than 2.0 mg/dL
• Cardiovascular: No symptomatic arteriosclerotic coronary artery disease; No history of coronary artery disease
• Other: Fasting triglyceride level less than 210 mg/dL; Fasting cholesterol level less than 350 mg/dL; No nonmalignant disease that would preclude administration of retinoids; No psychiatric conditions that would hinder compliance in this study; Not pregnant or nursing; Effective contraception required of all fertile patients during and for 6 months after study

Pennsylvania
      University of Pennsylvania Cancer Center, Philadelphia,  Pennsylvania,  19104,  United States

Study chairs or principal investigators

Lynn Mara Schuchter,  Study Chair,  Eastern Cooperative Oncology Group   

Study ID Numbers:  CDR0000066674; E-2695; NCI-P98-0134
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003601
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08