- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00000764
Chemoprevention of Anal Neoplasia Arising Secondary to Anogenital Human Papillomavirus Infection in Persons With HIV Infection.
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.
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment
Phase
- Phase 1
Contacts and Locations
Study Locations
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Washington
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Seattle, Washington, United States, 98122
- University of Washington AIDS CRS
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Palefsky JM
- Study Chair: Northfelt DW
- Study Chair: Kaplan LD
- Study Chair: Critchlow C
Study record dates
Study Major Dates
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- RNA Virus Infections
- Virus Diseases
- Blood-Borne Infections
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Neoplasms
- Neoplasms by Site
- Disease Attributes
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Intestinal Diseases
- DNA Virus Infections
- Intestinal Neoplasms
- Rectal Diseases
- Tumor Virus Infections
- Colorectal Neoplasms
- Slow Virus Diseases
- Rectal Neoplasms
- Anus Diseases
- HIV Infections
- Infections
- Communicable Diseases
- Acquired Immunodeficiency Syndrome
- Anus Neoplasms
- Papillomavirus Infections
- Physiological Effects of Drugs
- Anti-Infective Agents
- Antiviral Agents
- Antineoplastic Agents
- Immunologic Factors
- Dermatologic Agents
- Interferons
- Interferon-alpha
- Interferon alpha-2
- Isotretinoin
Other Study ID Numbers
- ACTG 216
- 11193 (Registry Identifier: DAIDS ES Registry Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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