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Patients 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 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.

Intensity-Modulated Radiation Therapy

Site Public Contact

Chia-Ching (Jackie) Wang

Sharad Goyal

Julian Sanchez

Yolande Chen

Lee Ratner

Rafi Kabarriti

Celina S. Ang

Patricia A. Locantore-Ford

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.

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.

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.

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.

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

Risk-Adapted Therapy for HIV-Associated Anal Cancer

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

Will be presented using descriptive statistics (with no inferential statistics involved).

Relationship with clinical response with be explored. Will be presented using descriptive statistics (with no inferential statistics involved).

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.

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.

Will be estimated using Kaplan-Meier method. The 95% confidence interval will be estimated using Greenwood's formula. The cumulative incidence of pelvic disease relapse will also be estimated from Kaplan-Meier method and the corresponding 90% confidence interval will be estimated using Greenwood's formula. In the analyses above, a two-sided p-value of 0.05 will be used to assess statistical significance.

Will be assessed by evaluating the changes from baseline in CD4+ using the Wilcoxon signed rank test to allow for nonnormality.

Will be assessed by evaluating the changes from baseline in HIV viral load using the Wilcoxon signed rank test to allow for nonnormality.

To assess cART adherence before, during, and after treatment with CRT and nivolumab to identify potential barriers to cART adherence when receiving concurrent oncological care.

National Cancer Institute (NCI)

Antibodies

Antibodies, Monoclonal

Immunomodulating Agents

Immunoglobulins

Patients from experimental group are underwent treatment together with PD-1 monoclonal antibody and radical CRT

Chemotherapy (/3w): 1)DDP 75 mg/m2, d1, intravenous infusion; 2)5-FU 1000 mg/m2, d1-4, continuous pumping intravenously; Immunotherapy (/3w): PD-1 monoclonal antibody(sintilimab) 200mg, d1, intravenous infusion; Radiotherapy (at 3rd week after first time of chemotherapy):Daily single dose of 2Gy, with a total dose of 50-54GY.

PD-1 and CRT

Jun Huang, MD

Fang He, MD

The goal of this clinical trial is to learn if PD-1 monoclonal antibody combined with radical chemoradiotherapy works to treat rectal squamous cell carcinoma (rSCC). lt will also learn about the safety of the regime. The main questions it aims to answer are:

Does PD-1 monoclonal antibody combined with radical chemoradiotherapy improve survival prognosis? What is the complete response rate (CCR) of the regime？ Researchers will compare PD-1 monoclonal antibody combined with radical chemoradiotherapy to previous study to see if this regime works to treat rSCCs.

Participants will receive chemotherapy with DDP and 5-FU, immunotherapy with PD-1 monoclonal antibody and radiotherapy with a total dose of 50-54GY.

Rectal squamous cell cancer (rSCC) is a rare malignancy, and its incidence is increasing year by year. Due to the rarity of rSCC, there is no consensus on its epidemiology, pathogenesis, prognosis and treatment management. Due to the limitation of clinical data, there is an urgent need for further clinical exploration and research.

In recent years, the combination of CRT and immunotherapy has attracted more and more attention, as they may have more advantages over CRT alone.A number of prospective clinical trials of PD-1 monoclonal antibody combined with CRT for the first-line treatment of advanced aSCC are also underway (NCT03233711, NCT04230759, NCT05661188, NCT05374252, etc.). Similarly, the efficacy and safety of PD-1 monoclonal antibody in rSCC patients are also worthy of further discussion, in order to further improve the survival prognosis of rSCC patients. Our previous study data showed that the 3-year OS and DFS of radical CRT were 88.9% and 66.7%, respectively, for non-metastatic rSCC, and 100% and DFS for radical CRT combined with immunotherapy, respectively, and CRT combined with immunotherapy significantly improved survival compared with radical CRT (P=0.02).

The goal of this clinical trial is to learn if PD-1 monoclonal antibody combined with radical chemoradiotherapy works to treat rectal squamous cell carcinoma (rSCC). lt will also learn about the safety of the regime. Therefore, we plan to conduct a multicenter, prospective, single-arm, phase II study to provide evidence-based medical evidence for the treatment of locally advanced rectal squamous cell carcinoma.

The primary outcome is 1-year tumor-free survival (DFS), and the secondary outcomes are including 1-year overall survival (OS), 1-year relapse-free survival (RFS), 1-year metastasis free survival (DMFS), 1-year stoma-free survival, incidence of chemotherapy and immunotherapy-related adverse reactions and complete response rate (CRR).

Participants will receive interventions below:

1. Chemotherapy (/3w): a)DDP 75 mg/m2, d1, intravenous infusion; b)5-FU 1000 mg/m2, d1-4, continuous pumping intravenously;
2. Immunotherapy (/3w): PD-1 monoclonal antibody(sintlimab) 200mg, d1, intravenous infusion;
3. Radiotherapy (at 3rd week after firstime of chemotherapy):Daily single dose of 2Gy, with a total dose of 50-54GY.

Radical Concurrent Chemoradiotherapy With DDP/5-FU and PD-1 Antibody for Non-metastatic Rectal Squamous Cell Carcinoma

Radical Concurrent Chemoradiotherapy With DDP/5-FU and PD-1 Antibody for Newly Diagnosed Non-metastatic Rectal Squamous Cell Carcinoma: A Multicenter, Prospective, Single Arm, Phase II Study(RICH).

The proportion of patients who do not have any of the following events from the beginning of randomization to the end of the first year

Time interval from the date of randomization to death

Time interval from the date of randomization to the onset of recurrence

Time interval from the date of randomization to the occurrence of distant metastases

The occurrence of chemotherapy and immune-related side effects during treatment

The proportion of the total number of patients with complete response after treatment to the total number of evaluable cases in solid tumor treatment studies

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Therapy Adapted for High Risk and Low Risk HIV-Associated Anal Cancer	NCT04929028	AIDS-Related An... Anal Basaloid S... Anal Canal Cloa... Anal Margin Squ... Anal Squamous C... HIV Infection Rectal Squamous... Stage I Anal Ca... Stage II Anal C... Stage II Rectal... Stage III Anal ... Stage III Recta...	Capecitabine Fluorouracil Intensity-Modul... Mitomycin Nivolumab	18 Years -	National Cancer Institute (NCI)
Radical Concurrent Chemoradiotherapy With DDP/5-FU and PD-1 Antibody for Non-metastatic Rectal Squamous Cell Carcinoma	NCT06364384	Rectal Squamous...	PD-1 and CRT	18 Years - 75 Years	Sixth Affiliated Hospital, Sun Yat-sen University

Spots Global Cancer Trial Database for rectal squamous cell carcinoma