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

This study has been completed.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000764
First received: November 2, 1999
Last updated: March 30, 2012
Last verified: March 2012

November 2, 1999
March 30, 2012
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Complete list of historical versions of study NCT00000764 on ClinicalTrials.gov Archive Site
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Chemoprevention of Anal Neoplasia Arising Secondary to Anogenital Human Papillomavirus Infection in Persons With HIV Infection.
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.

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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Efficacy Study
Primary Purpose: Treatment
  • HIV Infections
  • Anus Neoplasms
  • Drug: Isotretinoin
  • Drug: Interferon alfa-2a
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
98
July 1996
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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).

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00000764
ACTG 216, 11193
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Hoffmann-La Roche
Study Chair: Palefsky JM
Study Chair: Northfelt DW
Study Chair: Kaplan LD
Study Chair: Critchlow C
National Institute of Allergy and Infectious Diseases (NIAID)
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP