Chemoprevention of Anal Neoplasia Arising Secondary to Anogenital Human Papillomavirus Infection in Persons With HIV Infection.
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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.
Condition | Intervention | Phase |
---|---|---|
HIV Infections Anus Neoplasms |
Drug: Isotretinoin Drug: Interferon alfa-2a |
Phase 1 |
Study Type: | Interventional |
Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Primary Purpose: Treatment |
Official Title: | Chemoprevention of Anal Neoplasia Arising Secondary to Anogenital Human Papillomavirus Infection in Persons With HIV Infection. |
Estimated Enrollment: | 98 |
Study Completion Date: | July 1996 |
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.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts 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).
United States, Washington | |
University of Washington AIDS CRS | |
Seattle, Washington, United States, 98122 |
Study Chair: | Palefsky JM | |
Study Chair: | Northfelt DW | |
Study Chair: | Kaplan LD | |
Study Chair: | Critchlow C |
Additional Information:
No publications provided
Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
ClinicalTrials.gov Identifier: | NCT00000764 History of Changes |
Other Study ID Numbers: | ACTG 216, 11193 |
Study First Received: | November 2, 1999 |
Last Updated: | March 30, 2012 |
Health Authority: | United States: Federal Government |
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Interferon Alfa-2a Acquired Immunodeficiency Syndrome AIDS-Related Complex Anus Neoplasms |
Papillomavirus, Human Papovaviridae Infections Tumor Virus Infections Isotretinoin |
Additional relevant MeSH terms:
HIV Infections Acquired Immunodeficiency Syndrome Anus Neoplasms Neoplasms Warts Papillomavirus Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases |
Rectal Neoplasms Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Intestinal Diseases Anus Diseases Rectal Diseases DNA Virus Infections Skin Diseases, Viral Tumor Virus Infections Skin Diseases, Infectious |
ClinicalTrials.gov processed this record on February 26, 2013