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Active Not RecruitingNCT04929028

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

Risk-Adapted Therapy for HIV-Associated Anal Cancer

Status
Active Not Recruiting
Phase
Phase 2
Study type
Interventional
Enrollment
40 (estimated)
Sponsor
National Cancer Institute (NCI) · NIH
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

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.

Detailed description

PRIMARY OBJECTIVES: I. To determine the safety of reduced intensity chemo-radiation therapy (CRT) in low-risk disease. II. To determine the safety of nivolumab after standard CRT in high-risk disease. SECONDARY OBJECTIVES: I. To estimate the efficacy (2-year disease-control rate \[DCR\]) of reduced intensity CRT in low risk disease. II. To estimate the efficacy (2-year disease-free survival \[DFS\] rate) of nivolumab after standard CRT in high risk disease. III. To evaluate the effect of low-dose CRT on immune function (CD4+ cell count) and human immunodeficiency virus (HIV) viral load. IV. To evaluate the effect of nivolumab on immune function (CD4+ cell count) and HIV viral load. V. To assess combination antiretroviral therapy (cART) adherence before, during, and after treatment with CRT and nivolumab to identify potential barriers to cART adherence when receiving concurrent oncological care. EXPLORATORY OBJECTIVES: I. To determine the human papillomavirus (HPV) genotype in primary tumor and explore the relationship between specific HPV subtypes and clinical response to reduced intensity CRT or nivolumab. II. To explore the 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. III. To describe the effects of reduced intensity CRT and nivolumab on viral HIV reservoirs. IV. To identify the presence of cell-free plasma HPV deoxyribonucleic acid (DNA) before and after reduced intensity CRT and nivolumab and explore the relationship with clinical response. V. To describe the effect of reduced intensity CRT on quality of life (QOL). OUTLINE: Patients are assigned to 1 of 2 stratum. HIGH-RISK STRATUM: Patients receive nivolumab intravenously (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 echocardiography (ECHO) during screening as clinically indicated, sigmoidoscopy/colonoscopy, anoscopy/proctoscopy or digital rectal exam and computed tomography (CT) throughout the study as well as blood sample collection during screening and end of treatment (EOT). LOW-RISK STRATUM: Patients receive mitomycin IV on day 1 and either fluorouracil IV on day 1 or capecitabine orally (PO) twice daily (BID) on Monday-Friday until the completion of radiation therapy at the discretion of the treating physician. Patients also undergo intensity modulated radiation therapy (IMRT) once daily (QD) for 20-23 treatment sessions over 6 weeks. Patients also undergo digital rectal exam, anoscopy/proctoscopy and CT throughout the study, receive fludeoxyglucose F-18 (FDG) IV and undergo positron emission tomography (PET)/CT, PET/magnetic resonance imaging (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. After completion of study treatment, patients are followed up at 6 weeks, every 3 months for years 1-2, every 6 months for year 3, and then annually for years 4-5.

Conditions

Interventions

TypeNameDescription
PROCEDUREAnoscopyUndergo anoscopy
PROCEDUREBiospecimen CollectionUndergo blood sample collection
DRUGCapecitabineGiven PO
PROCEDUREColonoscopyUndergo colonoscopy
PROCEDUREComputed TomographyUndergo CT or FDG PET/CT
PROCEDUREDigital Rectal ExaminationUndergo digital rectal exam
PROCEDUREEchocardiography TestUndergo ECHO
OTHERFludeoxyglucose F-18Receive FDG
DRUGFluorouracilGiven IV
RADIATIONIntensity-Modulated Radiation TherapyUndergo IMRT
PROCEDURELymph Node BiopsyUndergo lymph node biopsy
PROCEDUREMagnetic Resonance ImagingUndergo MRI or PET/MRI
DRUGMitomycinGiven IV
BIOLOGICALNivolumabGiven IV
PROCEDUREPositron Emission TomographyUndergo FDG PET/CT or PET/MRI
PROCEDUREProctoscopyUndergo proctoscopy
OTHERQuestionnaire AdministrationAncillary studies
PROCEDURESigmoidoscopyUndergo sigmoidoscopy

Timeline

Start date
2022-08-09
Primary completion
2031-09-15
Completion
2031-09-15
First posted
2021-06-18
Last updated
2026-04-13

Locations

14 sites across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT04929028. Inclusion in this directory is not an endorsement.