Surgery in Treating Patients With Early Stage Anal Canal or Perianal Cancer and HIV Infection

January 19, 2024 updated by: AIDS Malignancy Consortium

A Multicenter Observational and Feasibility Study of Excision of Superficially Invasive Squamous Cell Carcinoma (SISCCA) of the Anal Canal and Perianus in HIV-Infected Persons

This phase II trial studies surgery in treating patients with anal canal or perianal cancer that is small and has not spread deeply into the tissues and human immunodeficiency virus (HIV) infection. Local surgery may be a safer treatment with fewer side effects than bigger surgery or radiation and chemotherapy.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the proportion of participants who develop treatment failure by 3 years is less than 25%, defined as the occurrence of distant or any nodal metastases or recurrence of cancer requiring chemotherapy (CMT), defined as a cancer that no longer meets the definition of superficially invasive squamous cell carcinoma (SISCCA) or a cancer that cannot be excised with a clear margin or preservation of sphincter function, or those who develop SISCCA recurrence but elect to undergo CMT rather than repeat excision in patients originally treated with excision of anal canal and perianal SISCCA.

II. To define the 1-year proportion of participants who develop incident anal squamous cancers at sites other than the location of the index SISCCA in patients treated with excision of anal canal and perianal SISCCA.

SECONDARY OBJECTIVES:

I. To determine morbidities associated with local excision of SISCCA and treatment of concomitant HSIL, including non-healing ulcer, fissure, persistent pain and bleeding, stricture, incontinence, and colostomy at 3 years after enrollment.

EXPLORATORY OBJECTIVES:

I. To determine the human papillomavirus (HPV) type in cancer and compare to that of overlying high-grade squamous intraepithelial lesions (HSIL) and HSIL biopsies collected concurrently that did not progress to cancer.

II. To determine and compare the HPV integration site in the anal cancer as well as in HSIL overlying or contiguous with the cancer and HSIL biopsies collected concurrently that did not progress to cancer.

III. Perform gene expression array analysis comparing expression in anal cancer with HSIL overlying or contiguous with the cancer.

IV. Perform gene expression array analysis comparing expression in HSIL biopsies that progressed to cancer with non-progressing HSIL biopsies at other locations.

V. Characterize genetic changes in anal cancers compared with HSIL overlying or contiguous with the cancer.

VI. Characterize genetic changes in HSIL biopsies that progressed to cancer compared with non-progressing HSIL biopsies at other locations.

VII. Perform gene expression array analysis and characterize genetic changes of SISCCAs that were cured with wide local excision for comparison with SISCCAs that progressed after wide local excision.

OUTLINE:

Patients undergo surgery to remove anal or perianal cancer. Any HSIL remaining is treated with the goal for complete eradication in accordance with clinician and participant preference.

After completion of study treatment, patients are followed up every 3 months for 36 months.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • University of California, San Francisco
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Grady Health System
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
    • New York
      • Bronx, New York, United States, 10461
        • Montefiore Medical Center
      • New York, New York, United States, 10011
        • Laser Surgery Care

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • A single, biopsy-proven SISCCA as defined by the LAST criteria (=< 3mm depth of invasion, horizontal spread of =< 7 mm, and completely excised with at least 1 mm margin clear of cancer irrespective of the amount of HSIL) documented per investigator assessment in combination with the pathology report within 12 months before Segment B enrollment.
  • No evidence of any lymph node spread or distant metastases as determined by PET CT imaging within 16 weeks before Segment B enrollment. Alternatively, for those without PET CT capability, an MRI or CT of the abdomen and pelvis and a chest x-ray confirming no evidence of metastatic disease is acceptable.
  • Clinician believes that eradication of concomitant HSIL is reasonable and feasible based on the extent of disease and overall medical condition of the subject
  • HIV-1 infection, as documented by one of the following: licensed HIV screening (antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 Western blot confirmation or HIV rapid multispot antibody differentiation assay, Documentation of HIV diagnosis in the medical record by a licensed HIV rapid test health care provider, HIV-1 RNA detection by a licensed HIV-1 RNA assay demonstrating >1000 RNA copies/mL, or Documentation of receipt of ART by a licensed health care provider.
  • Prior to Segment B enrollment, patients on combination anti-retroviral therapy (cART) will be required to have a minimum cluster of differentiation (CD)4 count of >= 200 and patients not on cART will be required to have a minimum CD4 count of >=350 to be eligible for the study; patients not currently on cART who have a CD4 count > 200 and who agree to start cART immediately will be eligible for participation; laboratory data should be obtained within 16 weeks prior to Segment B enrollment
  • Participants must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Participants must have a life expectancy of 2 years or more
  • Participants must not have any other concurrent malignancy
  • Participants must be age 18 years old or older.
  • Leukocytes: >= 3,000/mm^3
  • Absolute neutrophil count: >= 1,500/mm^3
  • Platelets: >= 100,000/mm^3
  • Women of childbearing potential must have a negative urine pregnancy test within 7 days prior to randomization enrollment; female participants enrolled in the treatment arm are advised to not become pregnant during study participation; all women of childbearing potential must agree to either commit to continued abstinence from heterosexual intercourse or use a reliable birth control method (oral contraceptive pills, intrauterine device, Nexplanon, DepoProvera, or bilateral tubal ligation, etc., or another acceptable method as determined by the investigator) during the entire period of the trial (5 years or more), and must not intend to become pregnant during study participation and for 3 months after treatment is discontinued if the participant is enrolled in the treatment arm.
  • Men should not father a child while in this study; men who could father a child must agree to use at least one form of birth control or continued abstinence from heterosexual intercourse if receiving topical treatment during during the study and for 2 weeks after stopping topical treatment
  • Participants must be able to understand and willing to sign a written informed consent document
  • Participants must, in the opinion of the Investigator, be capable of complying with the requirements of this protocol

Exclusion Criteria:

  • Anal cancer that cannot be completely excised with a >=1 mm clear margin from surrounding tissue or where excision to obtain a clear margin would compromise sphincter function or anal canal diameter
  • Concurrent anal canal or perianal HSIL or condyloma that in the judgment of the clinician cannot be cleared or can only be cleared with undue morbidity to the patient
  • No prior history of anal cancer, including SISCCA
  • Ongoing use of anticoagulant therapy other than aspirin or non-steroidal anti-inflammatory drugs (NSAIDS) that cannot be stopped for surgical procedures
  • Acute treatment for an infection (excluding fungal infection of the skin and sexually transmitted infections) or other serious medical illness within 2 weeks before enrollment
  • Current systemic chemotherapy or radiation therapy that potentially causes bone marrow suppression that would preclude safe treatment of HSIL; Note: Kaposi's sarcoma limited to the skin is not exclusionary unless requiring systemic chemotherapy
  • The participant's SISCCA must not have been ablated.
  • Participants who are receiving any other investigational agents within 4 weeks prior to enrollment. Investigational antiretroviral agents for HIV are acceptable.
  • Participant plans to relocate away from the study site during study participation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (surgery)
Participants undergo therapeutic conventional surgery to remove anal or perianal cancer (SISCCA). Any HSIL remaining is treated with the goal for complete eradication in accordance with clinician and participant preference.
Procedure: Therapeutic Conventional Surgery
Undergo surgery to remove anal or perianal cancer (SISCCA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To determine if the proportion of participants who develop treatment failure by 3 years is less than 25%.
Time Frame: 3 years after surgery to remove SISCCA
Treatment failure is specifically defined as the occurrence of distant or any nodal metastases or recurrence of cancer that no longer meets the definition of SISCCA and that cannot be excised with a clear margin or preservation of sphincter function and requires CMT, or those who develop SISCCA recurrence but elect to undergo CMT rather than repeat excision in patients originally treated with excision of anal canal and perianal SISCCA.
3 years after surgery to remove SISCCA

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The cumulative proportion of study participants who have experienced treatment failure by 3 years will be estimated using the product-limit estimate and its 95% confidence interval using Greenwood's formula.
Time Frame: 3 years after surgery to remove SISCCA
To determine morbidities associated with local excision of SISCCA and treatment of concomitant HSIL
3 years after surgery to remove SISCCA
The rate of treatment related adverse events including non-healing ulcer, fissure, persistent pain and bleeding, stricture, incontinence, and colostomy 6 months after excision of SISCCA.
Time Frame: 6 months after surgery to remove SISCCA
To determine morbidities associated with local excision of SISCCA and treatment of concomitant HSIL
6 months after surgery to remove SISCCA

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Collection of clinical specimens (composite)
Time Frame: Up to 36 months
Clinical specimens, specifically the index SISCCA and the overlying or adjacent HSIL, and HSIL that did not progress to SISCCA and other clinical data will be collected to create a bank of well-annotated specimens that will enable correlative science: to assess viral factors in HSIL progression to cancer and to identify host factors in HSIL progression to cancer.
Up to 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AIDS Malignancy Consortium

Collaborators

National Cancer Institute (NCI)
University of Arkansas
The Emmes Company, LLC
AIDS and Cancer Specimen Resource

Investigators

  • Principal Investigator: Stephen Goldstone, AIDS Associated Malignancies Clinical Trials Consortium

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2015

Primary Completion (Estimated)

March 21, 2026

Study Completion (Estimated)

March 21, 2026

Study Registration Dates

First Submitted

January 14, 2015

First Submitted That Met QC Criteria

May 7, 2015

First Posted (Estimated)

May 8, 2015

Study Record Updates

Last Update Posted (Actual)

January 22, 2024

Last Update Submitted That Met QC Criteria

January 19, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AMC-092 (Other Identifier: CTEP)
  • U01CA121947 (U.S. NIH Grant/Contract)
  • NCI-2014-02056 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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