Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Anus Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Anus Diseases

Rectal Diseases

Anal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive nivolumab while on study. Patients undergo sigmoidoscopy, colonoscopy or anoscopy, proctoscopy or digital rectal exam, x-ray, CT scan, MRI, biopsy and blood sample collection throughout the study.

Patients undergo observation while on study. Patients undergo sigmoidoscopy, colonoscopy or anoscopy, proctoscopy or digital rectal exam, x-ray, CT scan, MRI, biopsy and blood sample collection throughout the study.

Biopsy

Biospecimen Collection

Colonoscopy

Computed Tomography

Digital Rectal Examination

High Resolution Anoscopy

Magnetic Resonance Imaging

Patient Observation

Proctoscopy

Sigmoidoscopy

X-Ray Imaging

Lakshmi Rajdev

This phase III trial investigates how well nivolumab after combined modality therapy works in treating patients with high risk stage II-IIIB anal cancer. 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.

PRIMARY OBJECTIVE:

I. To evaluate whether therapy with nivolumab following combined modality therapy (CMT) improves disease-free survival (DFS) compared with observation in patients with high risk anal carcinoma.

SECONDARY OBJECTIVES:

I. To compare nivolumab following combined modality therapy (CMT) with observation in patients with high risk anal carcinoma with regard to:

Ia. Objective response rate (complete \[CR\] and partial \[PR\]), stable disease and progression.

Ib. Severe toxicity interval. Ic. Colostomy-free survival. Id. Overall survival. Ie. Toxicity.

OUTLINE: Patients who received standard CMT are randomized to 1 of 2 arms.

ARM A: Patients receive nivolumab intravenously (IV) while on study.

ARM B: Patients undergo observation while on study

Patients undergo sigmoidoscopy, colonoscopy or anoscopy, proctoscopy or digital rectal exam, x-ray, computed tomography (CT) scan, magnetic resonance imaging (MRI), biopsy and blood sample collection throughout the study.

Nivolumab After Combined Modality Therapy in Treating Patients With High Risk Stage II-IIIB Anal Cancer

A Randomized Phase III Study of Nivolumab After Combined Modality Therapy (CMT) in High Risk Anal Cancer

Will be defined as the occurrence of progression of local disease, distant metastases, second primary or death from the date of randomization.

Will be defined by complete and partial response.

The following late side effects are considered as severe: any anal/rectal damage (ulcer, fistula, or perforation), rectal stenosis that required colostomy, skin ulceration, and severe fibrosis. This parameter estimates the probability of being free of late side effects for patients under loco-regional control.

Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Canadian Cancer Trials Group

National Cancer Institute (NCI)

Infections

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Communicable Diseases

Acquired Immunodeficiency Syndrome

HIV Infections

Anti-Infective Agents

Fluorouracil

Capecitabine

Mitomycins

Mitomycin

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Alkylating Agents

Enzyme Inhibitors

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.

Recurrence

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Patients receive paclitaxel IV on days 1, 8, and 15 of each cycle, and carboplatin IV on day 1 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Patients receive nivolumab IV over 30 minutes on days 1 and 15 of cycle 1 and then on day 1 only of subsequent cycles, paclitaxel IV on days 1, 8, and 15 of each cycle, and carboplatin on day 1 of each cycle. Treatment repeats every 28 days for up to 6 cycles for carboplatin and paclitaxel, and up to 2 years for nivolumab in the absence of disease progression or unacceptable toxicity.

John A. Ellerton

Shahzad Siddique

Gary L. Buchschacher

Tatjana Kolevska

Syma Iqbal

Jun Gong

Jennifer B. Valerin

Gregory A. Masters

Mohamedtaki A. Tejani

Christopher M. Reynolds

Ranjith B. Dissanayake

Boris Naraev

Josh D. Simmons

Cathy Eng

This phase 3 trial compares the addition of nivolumab to chemotherapy (carboplatin and paclitaxel) versus usual treatment (chemotherapy alone) for the treatment of anal cancer that has spread to other places in the body (metastatic). 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. Chemotherapy drugs, such as carboplatin and paclitaxel, 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 nivolumab together with carboplatin and paclitaxel may help doctors find out if the treatment is better or the same as the usual approach.

PRIMARY OBJECTIVE:

I. To demonstrate that anti-PD-1 therapy in combination with carboplatin/weekly paclitaxel results in improved progression-free survival (PFS) versus systemic chemotherapy alone.

SECONDARY OBJECTIVES:

I. To demonstrate that anti-PD-1 therapy in combination with carboplatin/weekly paclitaxel results in improved overall survival (OS) versus systemic chemotherapy alone.

II. To demonstrate that anti-PD-1 therapy in combination with carboplatin/weekly paclitaxel results in improved objective response using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 versus systemic chemotherapy alone.

III. To evaluate toxicity profiles of the two regimens.

OUTLINE: Patients are randomized to 1 of 2 arms. Randomization will be 2:1 favoring the experimental regimen, Arm B.

ARM A: Patients receive paclitaxel intravenously (IV) on days 1, 8, and 15 of each cycle, and carboplatin IV on day 1 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive nivolumab IV over 30 minutes on days 1 and 15 of cycle 1 and then on day 1 only of subsequent cycles, paclitaxel IV on days 1, 8, and 15 of each cycle, and carboplatin on day 1 of each cycle. Treatment repeats every 28 days for up to 6 cycles for carboplatin and paclitaxel, and up to 2 years for nivolumab in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 month, then every 3 months for 2 years.

EA2176: Phase 3 Clinical Trial of Carboplatin and Paclitaxel +/- Nivolumab in Metastatic Anal Cancer Patients

A Randomized Phase III Study of Immune Checkpoint Inhibition With Chemotherapy in Treatment-Naive Metastatic Anal Cancer Patients

Defined as the first of progressive disease or death due to any cause. Analyzed using a stratified two-sided overall 0.05 level log-rank test. Will utilize standard Eastern Cooperative Oncology Group -American College of Radiology Imaging Network interim monitoring for efficacy evaluation.

ORR is the ratio of the number of patients with a complete response or partial response, as defined by Response Evaluation Criteria in Solid Tumors version 1.1, to the total number of treated patients.

Evaluated by a stratified log-rank test, and using a two-sided 0.05 level Cochran Mantel-Haenzel.

Analyses of toxicity will be via frequency tabulations and percentages by worst degree of toxicity and comparisons will be done via chi-square or Fisher's exact tests as appropriate.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nivolumab After Combined Modality Therapy in Treating Patients With High Risk Stage II-IIIB Anal Cancer	NCT03233711	Anal Basaloid S... Anal Canal Cloa... Anal Margin Squ... Stage IIB Anal ... Stage III Anal ...	Biopsy Biospecimen Col... Colonoscopy Computed Tomogr... Digital Rectal ... High Resolution... Magnetic Resona... Nivolumab Patient Observa... Proctoscopy Sigmoidoscopy X-Ray Imaging	18 Years -	National Cancer Institute (NCI)
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)
EA2176: Phase 3 Clinical Trial of Carboplatin and Paclitaxel +/- Nivolumab in Metastatic Anal Cancer Patients	NCT04444921	Anal Basaloid S... Anal Canal Cloa... Metastatic Anal... Recurrent Anal ... Stage III Anal ... Stage IV Anal C... Unresectable An...	Carboplatin Nivolumab Paclitaxel	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for anal basaloid squamous cell carcinoma