Therapy Adapted for High Risk and Low Risk HIV-Associated Anal Cancer

Running, not enrolling · Phase 2

Conditions studied: AIDS-Related Anal Carcinoma, Anal Margin Squamous Cell Carcinoma, Anal Non-Keratinizing Squamous Cell Carcinoma, Anal Squamous Cell Carcinoma, HIV Infection, Rectal Squamous Cell Carcinoma, Stage II Rectal Cancer AJCC v8, Stage IIB Anal Cancer AJCC v8, Stage III Anal Cancer AJCC v8, Stage III Rectal Cancer AJCC v8

In brief

This phase II trial studies the side effects of chemotherapy and intensity modulated radiation therapy in treating patients with low-risk HIV-associated anal cancer, and nivolumab after standard of care chemotherapy and radiation therapy in treating patients with high-risk HIV-associated anal cancer. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as mitomycin, fluorouracil, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with radiation therapy may kill more tumor cells. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving nivolumab after standard of care chemotherapy and radiation therapy may help reduce the risk of the tumor coming back.

Key facts

Study ID

NCT04929028

Run by

National Cancer Institute (NCI)

People needed

40

Starts

2022-08-09

Expected to finish

2031-09-15

Last updated by the study team

2026-06-17

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• HIGH-RISK STRATUM: Participant is able to understand and willing to sign a written informed consent document
• HIGH-RISK STRATUM: Participant must have histologically proven stage (T3-T4N0M0 OR T2-4N1M0) invasive squamous cell carcinoma (SCC) of the anus or anorectum as documented before CRT initiation, according to the American Joint Committee on Cancer (AJCC) 8th edition. Participants with squamous cell carcinoma of the anal margin are eligible if there is evidence of extension of the primary tumor into the anal canal. Participants with tumors of non-keratinizing histology such as basaloid, transitional cell or cloacogenic histology are permitted
• HIGH-RISK STRATUM: 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. If the record contains information that the patient is taking Food and Drug Administration (FDA)-approved combination therapy for HIV infection, then this can be part of the record substantiating the HIV positive diagnosis
• 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: The term "licensed" refers to a kit that has been certified or licensed by an oversight body within the participating country and validated internally (e.g., United States [U.S.] FDA)
• WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test must be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load
• HIGH-RISK STRATUM: Age >= 18 years
• Because no dosing or adverse event data are currently available on the use of nivolumab in participants < 18 years of age, children are excluded from this study
• HIGH-RISK STRATUM: Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 50%)
• HIGH-RISK STRATUM: Life expectancy of greater than 6 months
• HIGH-RISK STRATUM: Hemoglobin > 10 g/dL (within 2 weeks before enrollment)
• HIGH-RISK STRATUM: Absolute neutrophil count: >= 1,500/mm\^3 (within 2 weeks before enrollment)
• HIGH-RISK STRATUM: Platelets: >= 100,000/mm\^3 (within 2 weeks before enrollment)
• HIGH-RISK STRATUM: Total bilirubin: < 2 X upper limit of normal (ULN) (within 2 weeks before enrollment)
• HIGH-RISK STRATUM: Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]): =< 2.5 X institutional ULN (within 2 weeks before enrollment)
• HIGH-RISK STRATUM: Albumin >= 3.0 g/dL (within 2 weeks before enrollment)
• HIGH-RISK STRATUM: Creatinine levels =< 1.5 X normal institutional limits; or calculated creatinine clearance must be > 50 ml/min (within 2 weeks before enrollment)
• HIGH-RISK STRATUM: Females of childbearing potential (FOCBP) must agree to follow contraception requirements:
• The effects of nivolumab on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, FOCBP must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) before study entry, for the duration of study participation and 5 months after completion of nivolumab administration. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately
• NOTE: A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• HIGH-RISK STRATUM: Participant must have a CD4 count of >= 100 cells/uL at least 2 weeks prior to enrollment OR >= 100 cells/uL before receiving prior CRT, as CD4 may be low due to the effects of CRT
• HIGH-RISK STRATUM: Participant must be on a stable antiretroviral therapy (ART) regimen for at least 2 weeks prior to enrollment with no intention to change the regimen within 12 weeks after enrollment
• HIGH-RISK STRATUM: Participant must have an HIV RNA viral load of < 200 copies/mL

You may not qualify if…

• HIGH-RISK STRATUM: Any live vaccines within 30 days prior to enrollment
• Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines and are not allowed
• NOTE: No live vaccines may be administered while participating in the trial.
• HIGH-RISK STRATUM: Participant has known interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
• HIGH-RISK STRATUM: Prior treatment with an immune checkpoint inhibitor (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4 monoclonal antibody)
• HIGH-RISK STRATUM: Participant with an allogenic bone marrow/stem, cell or solid organ transplant
• HIGH-RISK STRATUM: Participant is receiving any other investigational agents
• HIGH-RISK STRATUM: History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab or other agents used in study
• HIGH-RISK STRATUM: Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements
• HIGH-RISK STRATUM: Participant has a history of a different malignancy, unless he/she have been disease-free for at least 2 years and are deemed by the investigator to be at low risk of recurrence
• NOTE: Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, basal cell or squamous cell carcinoma of the skin, and stage I and IIA/IIB resected melanoma. In addition, participants on hormonal treatment for breast/gynecological and prostate tumors with no evidence of active disease are permitted, as well as participants with controlled Kaposi sarcoma (KS) not requiring systemic KS directed therapy
• HIGH-RISK STRATUM: Pregnant or breastfeeding.
• Pregnant women are excluded from this study because nivolumab is an anti-PD-1MAb agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with nivolumab, breastfeeding should be discontinued if the mother is treated with nivolumab
• All FOCBP must have a blood test or urine study within 2 weeks prior to enrollment to rule out pregnancy
• HIGH-RISK STRATUM: Participant has not recovered from adverse events due to CRT (i.e., have residual toxicity > grade 1), excluding alopecia
• HIGH-RISK STRATUM: Participant has had prior potentially curative surgery (i.e., abdominal-perineal resection) for carcinoma of the anus
• HIGH-RISK STRATUM: Participant is receiving other standard anti-cancer therapy or experimental agent concurrently with the study drugs
• HIGH-RISK STRATUM: Participant has a known autoimmune disease
• Participants with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded. These include but are not limited to participants with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and participants with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease. Participants with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Participants with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and participants with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
• HIGH-RISK STRATUM: Participant requires steroid treatment or other immunosuppressive treatment
• Participants will be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 7 days of study drug administration. Topical corticosteroid or occasional inhaled corticosteroids are allowed
• HIGH-RISK STRATUM: Any surgery must have been completed >= 4 weeks before treatment initiation
• LOW-RISK STRATUM: Has undergone prior potentially curative surgery (i.e., abdominal-perineal resection) for carcinoma of the anus
• LOW-RISK STRATUM: Receiving any other standard anti-cancer therapy or investigational agents concurrently with study therapy
• LOW-RISK STRATUM: Significant cardiovascular disease including myocardial infarction, unstable angina, stroke, transient ischemic attack, symptomatic coronary artery disease, symptomatic congestive heart failure, or uncontrolled cardiac arrhythmia within 6 months of enrollment

Where it is running

• Zuckerberg San Francisco General Hospital — San Francisco, California, United States
• George Washington University Medical Center — Washington D.C., District of Columbia, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• University of Illinois — Chicago, Illinois, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• Mount Sinai West — New York, New York, United States
• Icahn School of Medicine at Mount Sinai — New York, New York, United States
• Mount Sinai Hospital — New York, New York, United States
• Montefiore Medical Center-Einstein Campus — The Bronx, New York, United States
• Montefiore Medical Center - Moses Campus — The Bronx, New York, United States
• Pennsylvania Hospital — Philadelphia, Pennsylvania, United States
• Lyndon Baines Johnson General Hospital — Houston, Texas, United States
• UT MD Anderson Cancer Center — Houston, Texas, United States
• Virginia Mason Medical Center — Seattle, Washington, United States

Full record on ClinicalTrials.gov

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