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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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HIV Infections, Anus Neoplasms

Intervention / Treatment
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* Drug: Isotretinoin
* Drug: Interferon alfa-2a


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Isotretinoin|nan|
|Drug: Interferon alfa-2a|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anus Neoplasms, Isotretinoin, Interferon Alfa-2a, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Papillomavirus, Human, Papovaviridae Infections, Tumor Virus Infections