Chemoprevention of Anal Neoplasia Arising Secondary to Anogenital Human Papillomavirus Infection in Persons With HIV Infection.


Phase 1
18 Years
N/A
Not Enrolling
Both
HIV Infections, Anus Neoplasms

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Trial Information

Chemoprevention of Anal Neoplasia Arising Secondary to Anogenital Human Papillomavirus Infection in Persons With HIV Infection.


Patients with HIV infection have a significant risk of recurrence following local ablation
of intraepithelial neoplasia; thus, anogenital epithelial may become an increasingly
important cause of morbidity, and possibly mortality, as the HIV epidemic matures. Clinical
studies of non-HIV-infected subjects have established that synthetic retinoids inhibit the
progression of epithelial preneoplastic conditions and some neoplastic states.

In the Phase I portion of the study, 20 patients per site each receive isotretinoin in
escalating doses. If a patient experiences grade 2 or worse toxicity (or grade 3 or worse
hypertriglyceridemia), dose is reduced to the previously tolerated dose for the remainder of
the 6 week period. Patients are then reassessed for anal neoplasia; those with no
progression and no grade 2 or worse toxicity receive an additional 6 weeks of isotretinoin
in combination with interferon alfa-2a. For Phase II of the study, a separate group of
patients who have undergone ablative therapy are randomized to one of three arms (26
patients/arm): isotretinoin alone at the dose tolerated by at least 60 percent of patients
in Phase I; isotretinoin plus interferon alfa-2a; or observation only. Treatment continues
for 48 weeks.

Inclusion Criteria


Inclusion Criteria

Concurrent Medication:

Allowed:

- PCP prophylaxis (required for patients with CD4 count < 200 cells/mm3).

- Chemoprophylaxis for candidiasis and herpes simplex.

- Metronidazole for up to 14 days.

- Erythropoietin.

Patients must have:

- HIV seropositivity.

- NO active opportunistic infection requiring treatment with prohibited drugs.

- Phase I - Current grade 1 AIN (i.e., low grade SIL) OR treated or untreated grade 2
or 3 AIN (i.e., high grade SIL).

Phase II - Prior histologically confirmed grade 2 or 3 AIN / high grade SIL, with ablative
therapy within the past 30-90 days.

- Capability of complying with study protocol.

NOTE:

- The terms condyloma, grade 1 AIN, and low grade SIL are interchangeable. Grade 2 or 3
AIN is interchangeable with high grade SIL.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

- Active medical problems for which the patient is undergoing evaluations or for which
prohibited therapy is required.

- Other active malignancies requiring systemic therapy.

- Significant symptomatic cardiac disease.

NOTE:

- Patients with malignancies being managed with local therapy (e.g., Kaposi's sarcoma,
basal cell carcinoma) may enroll at the discretion of the site investigator.

Concurrent Medication:

Excluded:

- G-CSF (filgrastim).

- Myelosuppressive antibiotics (except co-trimoxazole for PCP prophylaxis).

- Corticosteroids.

- Biologic response modifiers.

- Cytotoxic chemotherapy.

Concurrent Treatment:

Excluded:

- Radiation therapy.

Patients with the following prior conditions are excluded:

History of ventricular arrhythmias or myocardial infarction.

Prior Medication:

Excluded within 20 days prior to study entry:

- G-CSF (filgrastim).

- Myelosuppressive antibiotics (except co-trimoxazole for PCP prophylaxis).

- Corticosteroids.

- Biologic response modifiers.

- Cytotoxic chemotherapy.

Prior Treatment:

Excluded within 20 days prior to study entry:

- Radiation therapy.

Excluded within 14 days prior to study entry:

- Transfusion.

Active substance abuse or illegal drug use (alcohol consumption is strongly discouraged).

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Primary Purpose: Treatment

Principal Investigator

Palefsky JM

Investigator Role:

Study Chair

Authority:

United States: Federal Government

Study ID:

ACTG 216

NCT ID:

NCT00000764

Start Date:

Completion Date:

July 1996

Related Keywords:

  • HIV Infections
  • Anus Neoplasms
  • Interferon Alfa-2a
  • Acquired Immunodeficiency Syndrome
  • AIDS-Related Complex
  • Anus Neoplasms
  • Papillomavirus, Human
  • Papovaviridae Infections
  • Tumor Virus Infections
  • Isotretinoin
  • HIV Infections
  • Acquired Immunodeficiency Syndrome
  • Anus Neoplasms
  • Neoplasms
  • Warts
  • Papillomavirus Infections

Name

Location
University of Washington AIDS CRS Seattle, Washington  98122