Chemoprevention of Anal Neoplasia Arising Secondary to Anogenital Human Papillomavirus Infection in Persons With HIV Infection.
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections; Anus Neoplasms
Intervention: Isotretinoin (Drug); Interferon alfa-2a (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Palefsky JM, Study Chair
Northfelt DW, Study Chair
Kaplan LD, Study Chair
Critchlow C, Study Chair
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.
Clinical Details
Official title: Chemoprevention of Anal Neoplasia Arising Secondary to Anogenital Human Papillomavirus Infection in Persons With HIV Infection.
Study design: Treatment, Randomized, Efficacy Study
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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).
Locations and Contacts
San Francisco AIDS Clinic / San Francisco Gen Hosp, San Francisco, California 941102859, United States
Univ of Washington, Seattle, Washington 981224304, United States
Additional Information
Click here for more information about Interferon alfa-2a
Last updated: June 23, 2005
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