Clinical trial NCT00000758: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Cervix, Dysplasia
Keywords: Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Fluorouracil
Cervix Dysplasia
Cervix Diseases
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Hoffmann-La Roche
First posted: 2001-08-31
Enrollment: 158
Sex: FEMALE
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Usc La Nichd Crs
state: California
city: Miami
country: United States
facility: Univ. of Miami AIDS CRS
state: Florida
city: Chicago
country: United States
facility: Northwestern University CRS
state: Illinois
city: Chicago
country: United States
facility: Cook County Hosp. CORE Ctr.
state: Illinois
city: Chicago
country: United States
facility: Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease
state: Illinois
city: New Orleans
country: United States
facility: Tulane/LSU Maternal/Child CRS
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Adult AIDS CRS
state: Maryland
city: Boston
country: United States
facility: Bmc Actg Crs
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Med. Ctr., ACTG CRS
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hospital of Michigan NICHD CRS
state: Michigan
city: Newark
country: United States
facility: NJ Med. School CRS
state: New Jersey
city: Bronx
country: United States
facility: Bronx-Lebanon Hosp. IMPAACT CRS
state: New York
city: Buffalo
country: United States
facility: SUNY - Buffalo, Erie County Medical Ctr.
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Ctr.
state: New York
city: Rochester
country: United States
facility: Univ. of Rochester ACTG CRS
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Med. Univ., Dept. of Peds.
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs
state: North Carolina
city: Cincinnati
country: United States
facility: Univ. of Cincinnati CRS
state: Ohio
city: Seattle
country: United States
facility: UW School of Medicine - CHRMC
state: Washington
city: San Juan
country: Puerto Rico
facility: Puerto Rico-AIDS CRS
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp. PR NICHD CRS
Study officials:
name: Maiman M
role: STUDY_CHAIR
name: Watts DH
role: STUDY_CHAIR
References:
citation: Robinson WR, Morris CB. Cervical neoplasia. Pathogenesis, diagnosis, and management. Hematol Oncol Clin North Am. 1996 Oct;10(5):1163-76. doi: 10.1016/s0889-8588(05)70391-9.
citation: 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)