RATIONALE: Tretinoin may help cervical neoplasia cells develop into normal cervical cells. It is not yet known whether tretinoin is more effective than a placebo in preventing cervical cancer in patients with cervical neoplasia. PURPOSE: Randomized clinical trial to study the effectiveness of tretinoin in preventing cervical neoplasia from developing into cervical cancer.

Condition	Treatment or Intervention
Cervical Cancer	Drug: chemoprevention of cancer  Procedure: cancer prevention intervention  Drug: tretinoin

Further Study Details: 

OBJECTIVES: I. Determine whether topical tretinoin reduces the number of viral genome copies of human papilloma virus (HPV) per cell and inhibits HPV E6/E7 gene expression in patients with cervical dysplasia. II. Determine the dose of tretinoin for use in a definitive trial that produces the best overall modulation of these biomarkers.

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are stratified according to cervical intraepithelial neoplasia classification (II vs III). Patients are randomized to 1 of 4 arms. Arm I: Patients receive low-dose tretinoin topically via cervical cap and polyurethane ether foam sponge changed daily for 4 days. Arm II: Patients receive intermediate-dose tretinoin as in arm I. Arm III: Patients receive high-dose tretinoin as in arm I. Arm IV: Patients receive placebo topically as in arm I therapy. Patients are followed for 6 months.

PROJECTED ACCRUAL: A total of 180 patients (45 per arm) will be accrued for this study.

Ages Eligible for Study:  14 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven cervical dysplasia (cervical intraepithelial neoplasia II or III); Lesions must be delineated after colposcopic biopsy
• No pap smears suspicious for invasive carcinoma
• No positive endocervical curettage

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: At least 1 week since prior tretinoin; No prior retinoids (greater than 25,000 IU vitamin A or equivalent for at least 3 months); No other tretinoin during or for 3 months after study
• Endocrine therapy: No concurrent regular steroids
• Radiotherapy: Not specified
• Surgery: See Disease Characteristics
• Other: No concurrent regular anticoagulant medication; No concurrent nutritional supplements other than 2 multivitamins per day

--Patient Characteristics--

• Age: Over 14
• Performance status: Karnofsky 80-100%
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Not specified
• Renal: Not specified
• Immunologic: No proliferative skin disorder (e.g., psoriasis); No diagnosed autoimmune disorders; No allergy to tretinoin or latex
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception (except intrauterine device) during and for 3 months after study; Normal diet with adequate protein and carbohydrate intake; No in-utero exposure to diethylstilbesterol; No prior malignancy; No prior toxic shock syndrome

Michigan
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0752,  United States

Study chairs or principal investigators

Mack T. Ruffin, IV,  Study Chair,  University of Michigan Comprehensive Cancer Center   

Study ID Numbers:  CDR0000066670; CCUM-9609; NCI-P98-0131
Record last reviewed:  December 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003598
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08