Therapy Adapted for High Risk and Low Risk HIV-Associated Anal Cancer
Risk-Adapted Therapy for HIV-Associated Anal Cancer
3 other identifiers
interventional
40
1 country
14
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Aug 2022
Longer than P75 for phase_2
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 16, 2021
CompletedFirst Posted
Study publicly available on registry
June 18, 2021
CompletedStudy Start
First participant enrolled
August 9, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 15, 2031
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 15, 2031
May 13, 2026
April 1, 2026
9.1 years
June 16, 2021
May 12, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of adverse events (Low-risk stratum)
Evaluated by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The adverse events will be summarized by overall, as well as by grade using frequency (percentage). A two-sided 95% confidence interval will be reported together with percentage estimates. The proportion of participants who experience grade 3-4 toxicities will be estimated using a binomial point estimate and its 95% confidence interval.
Up to 5 years
Incidence of adverse events (High-risk stratum)
Evaluated by CTCAE version 5.0. The adverse events will be summarized by overall, as well as by grade using frequency (percentage). A two-sided 95% confidence interval will be reported together with percentage estimates. The proportion of participants who experience grade 3-4 toxicities will be estimated using a binomial point estimate and its 95% confidence interval.
Up to 5 years
Secondary Outcomes (5)
Disease free survival (High-risk stratum)
Time from enrollment until progression of local disease, distant metastasis, secondary primary cancer or death, assessed at 2 years
Disease control rate (Low-risk stratum)
Time from enrollment until first recurrence (locoregional or distant metastasis) or chemo-radiation-related death, assessed up to 5 years
Change in CD4+ cell counts (High-risk stratum)
Baseline up to 5 years
Change in human immunodeficiency virus (HIV) viral load (Low-risk stratum)
Baseline up to 5 years
Change in combination antiretroviral therapy (cART) adherence
Baseline up to 5 years
Other Outcomes (5)
Relationship between specific human papillomavirus (HPV) subtypes and clinical response to reduced intensity chemo-radiation therapy (CRT) or nivolumab
Up to 5 years
Relationship between expression of PD-1 in immune cells and PD-L1 in immune cells or cancer epithelial cells in the primary diagnostic tumor and clinical response to nivolumab or reduced intensity CRT
Up to 5 years
Effect of reduced intensity CRT and nivolumab on viral HIV reservoirs
Up to 5 years
- +2 more other outcomes
Study Arms (2)
High-risk stratum (nivolumab)
EXPERIMENTALPatients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO during screening as clinically indicated, sigmoidoscopy/colonoscopy, anoscopy/proctoscopy or digital rectal exam and CT throughout the study as well as blood sample collection during screening and EOT.
Low-risk stratum (mitomycin
EXPERIMENTALPatients receive mitomycin IV on day 1 and either fluorouracil IV on day 1 or capecitabine PO BID on Monday-Friday until the completion of radiation therapy at the discretion of the treating physician. Patients also undergo IMRT QD for 20-23 treatment sessions over 6 weeks. Patients also undergo digital rectal exam, anoscopy/proctoscopy and CT throughout the study, receive FDG IV and undergo PET/CT, PET/MRI and /or MRI during screening and follow-up as well as blood sample collection during screening and EOT. Some patients undergo lymph node biopsy during screening at the discretion of the treating physician.
Interventions
Undergo blood sample collection
Undergo FDG PET/CT or PET/MRI
Ancillary studies
Undergo sigmoidoscopy
Undergo lymph node biopsy
Undergo MRI or PET/MRI
Given IV
Undergo CT or FDG PET/CT
Undergo digital rectal exam
Undergo ECHO
Receive FDG
Given IV
Undergo IMRT
Given IV
Eligibility Criteria
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)
- +54 more criteria
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
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (14)
Zuckerberg San Francisco General Hospital
San Francisco, California, 94110, United States
George Washington University Medical Center
Washington D.C., District of Columbia, 20037, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
University of Illinois
Chicago, Illinois, 60612, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Mount Sinai West
New York, New York, 10019, United States
Icahn School of Medicine at Mount Sinai
New York, New York, 10029, United States
Mount Sinai Hospital
New York, New York, 10029, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Pennsylvania Hospital
Philadelphia, Pennsylvania, 19107, United States
Lyndon Baines Johnson General Hospital
Houston, Texas, 77026-1967, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Virginia Mason Medical Center
Seattle, Washington, 98101, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rafi Kabarriti
AIDS Malignancy Consortium
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 16, 2021
First Posted
June 18, 2021
Study Start
August 9, 2022
Primary Completion (Estimated)
September 15, 2031
Study Completion (Estimated)
September 15, 2031
Last Updated
May 13, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page