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
  Purpose

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.

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 98
Study Completion Date: July 1996
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000764

Locations
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98122
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Chair: Palefsky JM
Study Chair: Northfelt DW
Study Chair: Kaplan LD
Study Chair: Critchlow C
  More Information

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:
Acquired Immunodeficiency Syndrome
Anus Neoplasms
Communicable Diseases
HIV Infections
Infection
Neoplasms
Papillomavirus Infections
Anus Diseases
Colorectal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
DNA Virus Infections
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Immune System Diseases
Immunologic Deficiency Syndromes
Intestinal Diseases
Intestinal Neoplasms
Lentivirus Infections
Neoplasms by Site
Rectal Diseases
Rectal Neoplasms
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Tumor Virus Infections
Virus Diseases
Interferon-alpha

ClinicalTrials.gov processed this record on October 29, 2014