Anus Neoplasms, HIV Infections
Conditions
Keywords
Interferon Alfa-2a, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Anus Neoplasms, Papillomavirus, Human, Papovaviridae Infections, Tumor Virus Infections, Isotretinoin
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.
Interventions
DRUGIsotretinoin
Sponsors
Hoffmann-La Roche
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Countries
United States
Outcome results
None listed