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

PRIMARY OBJECTIVES:

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
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 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 patients 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.

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.

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 within 8 weeks
of enrollment

- No evidence of any lymph node spread or distant metastases as determined by positron
emission tomography (PET) computed tomography (CT) imaging within 8 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 subject

- HIV-1 infection, as documented by any federally approved, licensed HIV test performed
in conjunction with screening (or enzyme-linked immunosorbent assay [ELISA], test kit,
and confirmed by Western blot or other approved test); alternatively, this
documentation may include a record demonstrating that another physician has documented
the participant's HIV status based on either: 1) approved diagnostic tests or 2)
relevant medical history and/or current management of HIV infection

- Prior to Segment A 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 12 weeks prior to 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

- 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 72
hours prior to enrollment; female participants are advised to not become pregnant
during study participation; all women of childbearing potential must agree to use a
reliable birth control method (oral contraceptive pills, intrauterine device,
Nexplanon, DepoProvera, or permanent sterilization, etc., or another acceptable method
as determined by the investigator) during the entire period of the trial (3 years),
and must not intend to become pregnant during study participation and for 3 months
after treatment is discontinued

- 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 during the study and for 3 months
after stopping all study 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

- Prior pelvic radiation therapy that would preclude radiation therapy if anal cancer
develops

- 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

- Prior HPV vaccination

- Patients 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