What side effects are associated with this type of intervention?

Common treatments for Anal Squamous Cell Carcinoma include chemotherapy (e.g., carboplatin and paclitaxel) and immunotherapy with monoclonal antibodies such as Nivolumab. The side effects of chemotherapy can include nausea, vomiting, hair loss, fatigue, and increased risk of infection. Immunotherapy with Nivolumab can lead to immune-related adverse events such as skin rashes, colitis, hepatitis, endocrinopathies, and pneumonitis. These side effects arise from the enhanced immune response targeting not only cancer cells but also normal tissues.

What prior FDA approvals exist?

The FDA has approved several treatments for Anal Squamous Cell Carcinoma, primarily focusing on chemotherapy regimens. However, recent clinical trials, such as the one involving Nivolumab, are exploring the efficacy of immunotherapy with monoclonal antibodies. Nivolumab, an anti-PD-1 monoclonal antibody, is being studied in combination with chemotherapy agents like carboplatin and paclitaxel to enhance the immune system's ability to attack cancer cells and inhibit tumor growth and spread. This approach represents a promising advancement in the treatment landscape for metastatic anal cancer.

What other types of research exist?

Promising novel alternatives to Nivolumab for Anal Squamous Cell Carcinoma patients include other immune checkpoint inhibitors like Pembrolizumab and Atezolizumab, therapeutic vaccines targeting HPV, engineered T cells such as CAR-T cells, and antibody-drug conjugates. These treatments are in various stages of clinical development and may offer new options for patients in 2024.

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Alkylating agents

Nivolumab + Chemotherapy for Anal Cancer

Phase 3

Waitlist Available

Led By Cathy Eng

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

Patient must have histological or cytological confirmation of anal squamous cell carcinoma (includes basaloid and cloacogenic lesions) from the primary tumor or a newly diagnosed recurrent/metastatic lesion

Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

Must not have

Patient must not have active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including chronic prolonged systemic corticosteroids (defined as corticosteroid use of duration one month or greater). These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or anti-phospholipid syndrome. Patients with any of these are ineligible because of the risk of recurrence or exacerbation of autoimmune disease

Patient must not have a serious active infection requiring IV antibiotics at time of randomization

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing whether adding nivolumab to standard chemotherapy is more effective for patients with metastatic anal cancer. Nivolumab helps the immune system fight cancer, while chemotherapy kills or stops cancer cells from growing. Nivolumab has shown significant effectiveness in treating metastatic squamous cell carcinoma of the anal canal.

Who is the study for?

Adults with metastatic anal squamous cell carcinoma, including those HIV-positive on effective therapy or cured of hepatitis C. Participants must have measurable disease, be in good physical condition (ECOG 0-1), and not pregnant or breastfeeding. Excluded are those with recent major surgery, interstitial lung disease, active infections requiring IV antibiotics, certain autoimmune diseases, or prior systemic chemotherapy for metastatic anal cancer.

What is being tested?

This phase 3 trial is testing the effectiveness of adding nivolumab (an immunotherapy drug) to standard chemotherapy drugs carboplatin and paclitaxel in treating metastatic anal cancer. The goal is to see if this combination improves outcomes compared to chemotherapy alone.

What are the potential side effects?

Nivolumab may cause immune-related side effects such as inflammation in organs and infusion reactions. Chemotherapy can lead to hair loss, nausea, fatigue, increased risk of infection due to low blood counts, nerve damage causing numbness or tingling sensations.

Eligibility Criteria

Inclusion Criteria

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

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My cancer is confirmed as anal squamous cell carcinoma.

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I had hepatitis C but am cured, or I'm being treated with no detectable virus.

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My hepatitis B is under control or being treated effectively.

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I agree not to get any live vaccines during the study.

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I am HIV positive, on ART, with a CD4 count >= 200 or undetectable viral load.

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I am fully active or can carry out light work.

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My cancer cannot be removed by surgery and cannot be cured.

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I am 18 years old or older.

Exclusion Criteria

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

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I do not have an active or history of severe autoimmune disease.

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I do not have a serious infection needing IV antibiotics now.

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I have never received immunotherapy.

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I do not have a history of lung diseases like pneumonitis or pulmonary fibrosis.

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I do not have severe nerve damage.

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I have no allergies to platinum, taxane chemotherapy, or monoclonal antibodies.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 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

Progression-free survival

Secondary study objectives

Incidence of adverse events

Objective response rate (ORR)

Overall survival

Awards & Highlights

No Placebo-Only Group

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

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm B (carboplatin, paclitaxel, nivolumab)Experimental Treatment3 Interventions

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.

Group II: Arm A (carboplatin, paclitaxel)Active Control2 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nivolumab

2014

Completed Phase 3

~5220

Paclitaxel

2011

Completed Phase 4

~5810

Carboplatin

2014

Completed Phase 3

~6120

0 / 14Eligibility 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 Squamous Cell Carcinoma include chemotherapy and immunotherapy. Chemotherapy agents like carboplatin and paclitaxel work by killing cancer cells, inhibiting their division, and preventing their spread. Immunotherapy, particularly with monoclonal antibodies such as nivolumab, boosts the immune system's ability to attack cancer cells by targeting proteins that tumors use to evade immune detection. This combination of therapies is crucial for patients as it not only directly targets and destroys cancer cells but also enhances the body's natural immune response, potentially improving overall treatment efficacy and outcomes.

Human Papillomavirus Induced Cervical and Oropharyngeal Cancers: From Mechanisms to Potential Immuno-therapeutic Strategies.Cytoreductive treatment strategies for de novo metastatic prostate cancer.The State of Immune Checkpoint Inhibition in Urothelial Carcinoma: Current Evidence and Future Areas of Exploration.