Surgery in Treating Patients with Early Stage Anal Canal or Perianal Cancer and HIV Positive
- A single, biopsy-proven SISCCA as defined by the LAST criteria (=< 3 mm 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 16 weeks before Segment B enrollment
- No evidence of any lymph node spread or distant metastases as determined by positron emission tomography (PET) computed tomography (CT) imaging within 16 weeks of enrollment; alternatively, for those without PET CT capability, a magnetic resonance imaging (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 participant
- HIV positive; documentation of HIV-1 infection by means of any one of the following: * Documentation of HIV diagnosis in the medical record by a licensed health care provider; * Documentation of receipt of antiretroviral therapy (ART) by a licensed health care provider (documentation may be a record of an ART prescription in the participant’s medical record, a written prescription in the name of the participant for ART, or pill bottles for ART with a label showing the participant’s name; receipt of at least two agents is required; each component agent of a multi-class combination ART regimen will be counted toward the 2-agent requirement, excepting receipt of a pre-exposure prophylaxis [PrEP] regimen alone [e.g., Truvada], which is exclusionary); * HIV-1 ribonucleic acid (RNA) detection by a licensed HIV-1 RNA assay demonstrating > 1000 RNA copies/mL * Any 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 ** NOTE: A “licensed” assay refers to a United States (U.S.) Food and Drug Administration (FDA)-approved assay, which is required for all investigational new drug (IND) studies
- For females, documentation that the participant is being followed with cervical cytology and/or HPV testing per current “Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents” and American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines; cervical cytology must be performed prior to enrollment for women who are overdue for screening per the guidelines; women should also have confirmation of absence of cancer or suspected cancer upon visual examination of the vulva, vagina, and cervix within 12 months prior to enrollment
- Prior to Segment B enrollment, participants on combination anti-retroviral therapy (cART) will be required to have a minimum CD4 count of >= 200 and participants not on cART will be required to have a minimum CD4 count of >= 350 to be eligible for the study; participants 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 (Karnofsky performance status of 50% or greater)
- Participants must have a life expectancy of 2 years or more
- Participants must not have any other concurrent malignancy
- Participants must have organ and marrow function within the following parameters within 16 weeks before Segment B enrollment:
- Leukocytes: >= 3,000/mm^3
- Absolute neutrophil count: >= 1,500/mm^3
- Platelets: >= 100,000/mm^3
- Women of childbearing potential (FCBP)* 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 to use a reliable birth control method during heterosexual intercourse (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; female participants, if engaging in heterosexual intercourse, must be willing to comply with an acceptable birth control regimen as determined by the investigator * A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
- Men who could father a child must agree to use at least one form of birth control during or continued abstinence from heterosexual intercourse if receiving topical treatment 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
- 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
- The participant’s SISCCA must not have been ablated
- 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 participant
- 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 Segment B 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
- 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
I. To define the proportion of participants who develop treatment failure at 2 years, defined as the occurrence of distant or any nodal metastases or recurrence of cancer requiring combined modality therapy (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 participants 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 participants treated with excision of anal canal and perianal SISCCA.
I. To define the proportion of participants who develop treatment failure at 3 years, defined as occurrence of distant or any nodal metastases or recurrence of cancer requiring CMT, defined as a cancer that no longer meets the definition of 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 participants treated with excision of anal canal and perianal SISCCA.
II. To determine morbidities associated with local excision of SISCCA, including non-healing ulcer, fissure, persistent pain and bleeding, stricture, incontinence, and colostomy 6 months after excision of SISCCA.
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.
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.
Trial Phase Phase II
Trial Type Treatment
AIDS Malignancy Consortium
Stephen Elliot Goldstone
- Primary ID AMC-092
- Secondary IDs NCI-2014-02056, 092, AMC #092
- Clinicaltrials.gov ID NCT02437851