A Phase III Randomized Trial of Topical Vaginal Fluorouracil (5-Fluorouracil, 5-FU) Maintenance Therapy Versus Observation After Standard Treatment for High-Grade Cervical Dysplasia in HIV-Infected Women

HIV Infections Clinical Trial

Official title:

A Phase III Randomized Trial of Topical Vaginal Fluorouracil (5-Fluorouracil, 5-FU) Maintenance Therapy Versus Observation After Standard Treatment for High-Grade Cervical Dysplasia in HIV-Infected Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000758
• Other study ID #: ACTG 200
• Secondary ID: 11176
• Status: Completed
• Phase: Phase 3
• Est. completion date: April 1998

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To determine the efficacy and safety of intravaginal fluorouracil administered as prophylaxis in HIV-infected women who have received standard ablative therapy (surgery) for high-grade cervical dysplasia (pre-cancer of the cervix; cervical intraepithelial neoplasia). To correlate time to recurrence of cervical dysplasia with T-cell function.

Women with HIV infection are at greater risk for cervical dysplasia. Because of the likelihood that untreated or recurrent cervical dysplasia may progress to invasive cancer, there is an urgent need to develop appropriate therapies.

Description:

Women with HIV infection are at greater risk for cervical dysplasia. Because of the likelihood that untreated or recurrent cervical dysplasia may progress to invasive cancer, there is an urgent need to develop appropriate therapies.

Patients are randomized to receive either intravaginal fluorouracil or no treatment (observation only). Fluorouracil cream is self-administered via applicator at biweekly intervals for 6 months. Patients are evaluated for recurrent cervical dysplasia by cytology and colposcopy with or without biopsy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 158
• Est. completion date: April 1998
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 13 Years and older

Eligibility

Inclusion Criteria

Concurrent Medication:

Allowed:

• Antiretrovirals (AZT, ddI, ddC) and immunomodulators (interferon and interleukin).

• Prophylaxis or treatment for opportunistic infections.

• Vaginal antifungal agents or other indicated vaginal medications (although not permitted on day of fluorouracil application).

• Contraceptives.

• Acyclovir (prophylaxis or treatment) in patients with a history of primary or recurrent genital herpes.

Patients must have:

• HIV infection.

• Prior cervical dysplasia (grade II or III cervical intraepithelial neoplasia) successfully treated with an ablative procedure within the past 12 weeks.

• Patients less than 18 years of age must have consent of parent or guardian.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

• Untreated or persistent vaginal or vulvar dysplasia.

• Colposcopy or biopsy inconclusive or positive for dysplasia.

• Active genital ulcerative disease such as syphilitic chancre or herpes ulcer.

• Adenocarcinoma in situ.

Concurrent Medication:

Excluded:

• Cytotoxic chemotherapy for malignancy.

• High-dose steroids (> 10 mg/day prednisone or its steroid equivalent).

Patients with the following prior conditions are excluded:

• Malignancy requiring cytotoxic chemotherapy within the 3 months prior to study entry.

• Prior hysterectomy.

• History of allergic reaction or severe hypersensitivity to fluorouracil.

Prior Medication:

Excluded:

• Fluorouracil (systemic or topical) within 3 months prior to study entry.

Related Conditions & MeSH terms

• Cervical Intraepithelial Neoplasia
• Cervix, Dysplasia
• HIV Infections
• Hyperplasia
• Uterine Cervical Dysplasia

Intervention

Drug:
• Fluorouracil

Locations

Country	Name	City	State
Puerto Rico	Puerto Rico-AIDS CRS	San Juan
Puerto Rico	San Juan City Hosp. PR NICHD CRS	San Juan
United States	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland
United States	Beth Israel Deaconess Med. Ctr., ACTG CRS	Boston	Massachusetts
United States	Bmc Actg Crs	Boston	Massachusetts
United States	Bronx-Lebanon Hosp. IMPAACT CRS	Bronx	New York
United States	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York
United States	Unc Aids Crs	Chapel Hill	North Carolina
United States	Cook County Hosp. CORE Ctr.	Chicago	Illinois
United States	Northwestern University CRS	Chicago	Illinois
United States	Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease	Chicago	Illinois
United States	Univ. of Cincinnati CRS	Cincinnati	Ohio
United States	Children's Hospital of Michigan NICHD CRS	Detroit	Michigan
United States	Usc La Nichd Crs	Los Angeles	California
United States	Univ. of Miami AIDS CRS	Miami	Florida
United States	Tulane/LSU Maternal/Child CRS	New Orleans	Louisiana
United States	Memorial Sloan-Kettering Cancer Ctr.	New York	New York
United States	NJ Med. School CRS	Newark	New Jersey
United States	Univ. of Rochester ACTG CRS	Rochester	New York
United States	UW School of Medicine - CHRMC	Seattle	Washington
United States	SUNY Upstate Med. Univ., Dept. of Peds.	Syracuse	New York

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (2)

Maiman M, Watts DH, Andersen J. A phase three randomized trial of topical vaginal 5-fluorouracil maintenance therapy versus observation after standard treatment for high grade cervical dysplasia in HIV-infected women: ACTG 200. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:155 (abstract no 466)

Robinson WR, Morris CB. Cervical neoplasia. Pathogenesis, diagnosis, and management. Hematol Oncol Clin North Am. 1996 Oct;10(5):1163-76. Review. — View Citation