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

Primary Purpose

HIV Infections, Anus Neoplasms

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Isotretinoin
Interferon alfa-2a
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Interferon Alfa-2a, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Anus Neoplasms, Papillomavirus, Human, Papovaviridae Infections, Tumor Virus Infections, Isotretinoin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • University of Washington AIDS CRS

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 27, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT00000764
Brief Title
Chemoprevention of Anal Neoplasia Arising Secondary to Anogenital Human Papillomavirus Infection in Persons With HIV Infection.
Official Title
Chemoprevention of Anal Neoplasia Arising Secondary to Anogenital Human Papillomavirus Infection in Persons With HIV Infection.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
July 1996 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Hoffmann-La Roche

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Anus Neoplasms
Keywords
Interferon Alfa-2a, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Anus Neoplasms, Papillomavirus, Human, Papovaviridae Infections, Tumor Virus Infections, Isotretinoin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Allocation
Randomized
Enrollment
98 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Isotretinoin
Intervention Type
Drug
Intervention Name(s)
Interferon alfa-2a

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Palefsky JM
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Northfelt DW
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Kaplan LD
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Critchlow C
Official's Role
Study Chair
Facility Information:
Facility Name
University of Washington AIDS CRS
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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