Chemoprevention of Anal Neoplasia Arising Secondary to Anogenital Human Papillomavirus Infection in Persons With HIV Infection.
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 98
- Locations
- 1
Study Overview
Brief Summary
PRIMARY: In Phase I, to define a broadly tolerable dose of isotretinoin that can be used in combination with interferon alfa-2a (IFN alfa-2a). In Phase II, to determine trends in efficacy of isotretinoin alone or in combination with IFN alfa-2a as chemoprevention (preventing progression or recurrence) of anal intraepithelial neoplasia ( AIN ) / squamous intraepithelial lesions ( SIL ) in patients with HIV infection.
SECONDARY: To evaluate the effects of isotretinoin alone or in combination with IFN alfa-2a on immune function markers, human papillomavirus (HPV) type, and HPV DNA levels.
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.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Primary Purpose
- Treatment
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Concurrent Medication:
- •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.
- •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.
- •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:
- •G-CSF (filgrastim).
- •Myelosuppressive antibiotics (except co-trimoxazole for PCP prophylaxis).
- •Corticosteroids.
- •Biologic response modifiers.
- •Cytotoxic chemotherapy.
- •Concurrent Treatment:
- •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).