What side effects are associated with this type of intervention?

The most common treatments for anal carcinoma, particularly those involving immunotherapy with monoclonal antibodies like nivolumab, are associated with a range of side effects. These include immune-related adverse events (irAEs) such as dermatologic issues (rash, pruritus), gastrointestinal problems (diarrhea, colitis), hepatic effects (hepatitis), and endocrine disturbances (thyroid dysfunction). Additionally, patients may experience pneumonitis, which is inflammation of the lung tissue, and less commonly, ocular side effects like uveitis. These side effects arise from the general enhancement of the immune system, which can sometimes lead to the immune system attacking normal tissues.

What prior FDA approvals exist?

As of now, there are no specific FDA approvals for immunotherapy treatments like nivolumab specifically for anal carcinoma. However, immunotherapy with monoclonal antibodies, such as nivolumab, has been approved for other types of cancers, including melanoma and non-small cell lung cancer, where it helps the immune system attack cancer cells and may prevent tumor growth and spread. For anal carcinoma, standard treatments typically involve chemotherapy and radiation therapy, with ongoing trials investigating the efficacy of adding immunotherapy agents like nivolumab.

What other types of research exist?

For Anal Carcinoma patients considering treatment in 2024, promising novel alternatives to Nivolumab include other immune checkpoint inhibitors such as Pembrolizumab and Avelumab, which target PD-1 and PD-L1 respectively. Additionally, experimental approaches like chimeric antigen receptor (CAR)-T cell therapies are being tested and may offer new treatment options.

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Chemotherapy

Chemotherapy + Radiation for HIV-Associated Anal Cancer

Q: What is the mechanism of action of this treatment?

The most common treatments for Anal Carcinoma include chemotherapy, radiation therapy, and immunotherapy with monoclonal antibodies such as Nivolumab. Chemotherapy uses drugs like mitomycin, fluorouracil, and capecitabine to kill cancer cells, stop their division, or prevent their spread. Radiation therapy employs high-energy x-rays to destroy tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as Nivolumab, enhances the body's immune system to attack cancer cells and may inhibit tumor growth and spread. These treatments are often combined to maximize their effectiveness, offering a comprehensive approach to managing Anal Carcinoma and potentially reducing the risk of recurrence.

Phase 2

Recruiting

Led By Rafi Kabarriti

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participant must have =< grade 2 diarrhea

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

Must not have

Participant requires steroid treatment or other immunosuppressive treatment

Participant with an allogenic bone marrow/stem cell or solid organ transplant

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial studies the effects of chemotherapy, radiation, and immunotherapy in treating HIV-associated anal cancer. It targets both low-risk and high-risk patients, aiming to kill cancer cells and help the immune system prevent the cancer from coming back.

Who is the study for?

This trial is for adults with HIV-associated anal cancer. Low-risk patients have T1-2N0M0 tumors ≤4 cm, while high-risk patients have stage T3-T4N0M0 or T2-4N1M0 tumors. All must understand the study, sign consent, have a life expectancy over 6 months, adequate blood counts and organ function, be on stable HIV treatment with controlled viral load, agree to contraception if applicable, and not be pregnant or breastfeeding.

What is being tested?

The trial tests chemotherapy (mitomycin, fluorouracil/capecitabine) combined with intensity-modulated radiation therapy for low-risk anal cancer patients. High-risk patients receive standard care plus nivolumab post-treatment to reduce tumor recurrence risk. Nivolumab is an immunotherapy that may help the immune system fight cancer more effectively.

What are the potential side effects?

Chemotherapy can cause nausea, fatigue, hair loss and increased infection risk. Radiation might lead to skin irritation and fatigue. Nivolumab could result in immune-related side effects like inflammation of organs such as lungs or intestines and potential infusion reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My diarrhea is mild or moderate.

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I have a specific type of anal cancer that is at a certain stage and has not spread to distant parts of my body.

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I can take care of myself but might not be able to do heavy physical work.

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I am on a consistent HIV medication regimen.

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I have received radiation therapy for anal cancer.

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I am 18 years old or older.

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I have tested negative for tuberculosis.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I need steroids or other drugs that lower my immune system.

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I have had a bone marrow/stem cell or organ transplant from another person.

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I had surgery aimed at curing anal cancer.

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I have a history of cancer.

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I had a different cancer within the last 2 years.

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I have been treated with drugs that boost the immune system.

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I have been diagnosed with interstitial lung disease.

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I have received chemotherapy for my cancer before.

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I have had a condition where my lymphocytes grow abnormally.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of adverse events (High-risk stratum)

Incidence of adverse events (Low-risk stratum)

Secondary study objectives

Change in CD4+ cell counts (High-risk stratum)

Change in combination antiretroviral therapy (cART) adherence

Change in human immunodeficiency virus (HIV) viral load (Low-risk stratum)

+2 more

Other study objectives

Effect of reduced intensity CRT and nivolumab on viral HIV reservoirs

Impact of reduced intensity CRT on quality of life

Prevalence of cell-free plasma HPV deoxyribonucleic acid (DNA) before and after reduced intensity CRT and nivolumab

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Low-risk stratum (mitomycinExperimental Treatment17 Interventions

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. 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.

Group II: High-risk stratum (nivolumab)Experimental Treatment10 Interventions

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 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Anoscopy

2015

N/A

~10

Echocardiography

2013

Completed Phase 4

~11580

Computed Tomography

2017

Completed Phase 2

~2740

Sigmoidoscopy

2007

Completed Phase 2

~140

Colonoscopy

2012

Completed Phase 3

~115560

Proctoscopy

2012

Completed Phase 1

~10

Lymph Node Biopsy

2014

Completed Phase 2

~50

Magnetic Resonance Imaging

2017

Completed Phase 3

~1160

Biospecimen Collection

2004

Completed Phase 3

~2020

Positron Emission Tomography

2011

Completed Phase 2

~2200

Fluorouracil

2014

Completed Phase 3

~11700

Nivolumab

2015

Completed Phase 3

~4010

Mitomycin

2009

Completed Phase 3

~410

Capecitabine

2013

Completed Phase 3

~4280

Intensity-Modulated Radiation Therapy

2010

Completed Phase 3

~2160

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Anal Carcinoma include chemotherapy, radiation therapy, and immunotherapy with monoclonal antibodies such as Nivolumab. Chemotherapy uses drugs like mitomycin, fluorouracil, and capecitabine to kill cancer cells, stop their division, or prevent their spread. Radiation therapy employs high-energy x-rays to destroy tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as Nivolumab, enhances the body's immune system to attack cancer cells and may inhibit tumor growth and spread. These treatments are often combined to maximize their effectiveness, offering a comprehensive approach to managing Anal Carcinoma and potentially reducing the risk of recurrence.

Recurrent glioma clinical trial, CheckMate-143: the game is not over yet.