Nivolumab for Anal Cancer

Not currently recruiting at 1045 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immune checkpoint inhibitors, Immunosuppressants

Disqualifiers: Pregnancy, Transplant, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of the drug nivolumab after standard treatment in patients with high-risk stage II-IIIB anal cancer. Nivolumab, an immunotherapy, helps the immune system fight cancer and may stop tumor growth. Participants will either receive nivolumab or undergo clinical observation, with various medical tests conducted throughout the study. This trial may suit individuals with specific types of anal cancer who have completed chemoradiation therapy. As a Phase 3 trial, it represents the final step before potential FDA approval, offering participants a chance to contribute to the advancement of cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on systemic steroid therapy above a certain dose or receive live vaccines close to the trial period. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that nivolumab is generally well-tolerated by patients. In studies involving patients with advanced anal cancer, nivolumab produced promising results. Specifically, 9 out of 37 patients responded positively to the treatment. This indicates that many people can use the drug without serious issues.

Common side effects in previous trials included tiredness and skin rashes, which were usually mild and manageable. The FDA has already approved nivolumab for other conditions, supporting its safety. This provides strong evidence of its safety for humans, though, like any treatment, it may have some side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about nivolumab for anal cancer because it offers a new way to harness the body's immune system to fight cancer. Unlike standard treatments like chemotherapy and radiation, which directly attack cancer cells, nivolumab is an immune checkpoint inhibitor. It works by blocking a protein called PD-1 on immune cells, which helps the immune system recognize and destroy cancer cells. This mechanism can potentially lead to better outcomes and fewer side effects compared to traditional therapies.

What evidence suggests that nivolumab might be an effective treatment for anal cancer?

Research has shown that nivolumab, a type of immunotherapy, can help treat anal cancer. In studies with patients who had already tried other treatments, about 24% saw their cancer shrink or stop growing with nivolumab. This means roughly one in four patients experienced positive results. On average, patients lived about 4.1 months without their cancer worsening and about 11.5 months after starting treatment. In this trial, some participants will receive nivolumab, while others will undergo clinical observation. These results suggest that nivolumab can help the body's immune system fight anal cancer, offering a potential new option for those with high-risk stage II-IIIB anal cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Lakshmi Rajdev

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

Adults with high-risk stage II-IIIB anal cancer who have not had prior immune checkpoint inhibitor therapy, no recent transplants, autoimmune disease, or other cancers. HIV+ patients are eligible if well-managed. Participants must meet specific blood count and organ function criteria and agree to contraception.

Inclusion Criteria

Absolute neutrophil count (ANC) level of > 1500/mm^3 (within 2 weeks prior to registration)

Your blood test taken within 2 weeks before the study shows that your ANC level is above 1500/mm^3.

Your liver enzymes (AST and ALT) should not be more than 2.5 times the normal level. This will be checked within 2 weeks before you enroll in the study.

Exclusion Criteria

I am not taking any other cancer treatments or experimental drugs with the study drugs.

I have had chemoradiotherapy for anal cancer before.

I have lung disease that could affect my treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Combined Modality Therapy (CMT)

Participants receive standard combined modality therapy for anal cancer

6-8 weeks

Treatment

Participants receive nivolumab intravenously or undergo observation

Up to 5 years

Regular visits for sigmoidoscopy, colonoscopy, imaging, and blood sample collection

Follow-up

Participants are monitored for disease-free survival, objective response rate, and incidence of toxicities

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab

Trial Overview The trial is testing the effectiveness of nivolumab as an immunotherapy after standard treatment for anal cancer. It aims to see if nivolumab can help the immune system attack cancer cells better and prevent the disease from spreading.

How Is the Trial Designed?

Group I: Arm B (clinical observation) Experimental Treatment 10 Interventions

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.

Group II: Arm A (nivolumab) Experimental Treatment 11 Interventions

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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Canadian Cancer Trials Group

Collaborator

Trials

135

Recruited

70,300+

Published Research Related to This Trial

In the phase III CheckMate 238 trial, 67.7% of patients receiving nivolumab experienced treatment-related adverse events (TRAEs), with the most common being pruritus and diarrhea, primarily occurring within the first 3 months of treatment.

Despite the high incidence of TRAEs, there was no significant association found between these adverse events and recurrence-free survival (RFS), indicating that the safety profile of nivolumab remains consistent and does not negatively impact long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nivolumab for stage III/IV melanoma: evaluation of safety outcomes and association with recurrence-free survival. Mandala, M., Larkin, J., Ascierto, PA., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

Nivolumab (OPDIVO) was approved by the FDA for treating unresectable advanced esophageal squamous cell carcinoma (ESCC) after prior chemotherapy, showing a significant improvement in overall survival (10.9 months for nivolumab vs. 8.4 months for chemotherapy).

Patients treated with nivolumab experienced fewer treatment-emergent adverse events compared to those receiving chemotherapy, although there was a new risk of esophageal fistula and a higher incidence of pneumonitis in the ESCC population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit-Risk Summary of Nivolumab for the Treatment of Patients with Unresectable Advanced, Recurrent, or Metastatic Esophageal Squamous Cell Carcinoma After Prior Fluoropyrimidine- and Platinum-Based Chemotherapy. Pelosof, L., Saung, MT., Donoghue, M., et al.[2021]

In a study of 1266 anal cancer patients treated according to Nordic guidelines, the 3-year recurrence-free survival rate was between 63% and 76%, indicating effective treatment outcomes.

Factors such as older age, male gender, and larger tumors were linked to worse outcomes, and the study suggests that inguinal prophylactic irradiation should be considered even for small tumors to reduce recurrence rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anal carcinoma - Survival and recurrence in a large cohort of patients treated according to Nordic guidelines. Leon, O., Guren, M., Hagberg, O., et al.[2022]

Nivolumab, an anti-PD-1 antibody, was administered to a 63-year-old female patient with metastatic melanoma after renal transplantation, highlighting the potential for anti-tumor activity in high-risk patients, despite the challenges of concurrent immunosuppression.

The patient experienced acute renal allograft rejection and renal failure shortly after starting nivolumab, indicating significant risks associated with this treatment in transplant recipients, but she later showed a positive clinical response after re-challenging with nivolumab while on hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. Ong, M., Ibrahim, AM., Bourassa-Blanchette, S., et al.[2023]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

Nivolumab and pembrolizumab, both PD-1 inhibitors, show a lower risk of severe treatment-related adverse effects (AEs) compared to standard care, with a relative risk of 0.39 for grade 3/4 AEs based on a meta-analysis of 9 trials involving 5,353 patients.

While these therapies are generally well tolerated, they are associated with a significantly increased risk of thyroid dysfunction (hyperthyroidism and hypothyroidism) and skin conditions like pruritus and vitiligo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. Costa, R., Carneiro, BA., Agulnik, M., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, significantly improves overall survival and progression-free survival in patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CHECKMATE 017 study.

The safety and tolerability of nivolumab are favorable, and interestingly, the expression of the PD-L1 ligand does not predict treatment outcomes, suggesting that other factors may influence the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. Lim, JS., Soo, RA.[2018]

Nivolumab can cause immune-mediated colitis that resembles ulcerative colitis, as seen in a study of 19 patients, including 6 new cases and 13 previously reported cases, highlighting the need for careful diagnosis.

Most patients responded well to corticosteroid treatment, but about 25% required additional therapy with infliximab, indicating that while steroids are effective, some cases may need more intensive intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab-induced immune-mediated colitis: an ulcerative colitis look-alike-report of new cases and review of the literature. Cañete, F., Mañosa, M., Lobatón, T., et al.[2020]

Nivolumab is the first approved PD-1 inhibitor that helps the immune system fight against tumors, specifically for patients with unresectable melanoma.

Early phase studies have shown promising results for nivolumab in treating solid tumors like non-small cell lung cancer (NSCLC), especially when combined with chemotherapy and other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in NSCLC: latest evidence and clinical potential. Sundar, R., Cho, BC., Brahmer, JR., et al.[2022]

Nivolumab, an immune checkpoint inhibitor approved for treating various metastatic cancers, is associated with autoimmune-related side effects, particularly gastrointestinal issues like diarrhea and colitis.

This report highlights a previously unreported case of nivolumab-induced esophagitis and gastritis, suggesting that upper gastrointestinal adverse events may also occur with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe Esophagitis and Gastritis from Nivolumab Therapy. Boike, J., Dejulio, T.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5809128/

Nivolumab for previously treated unresectable metastatic anal ... Although the median progression-free survival was 4.1 months, the longest duration of treatment has been almost 1 year and is continuing as of the data cutoff ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e15502

Efficacy and safety of nivolumab in pretreated patients with ... Nivolumab was administered as a 2nd line treatment in 13 pts, while 2 pts received ICI in the 3rd line. Overall, median OS was 8.3 months (mo.) ...

3. onclive.com onclive.com/view/nivolumab-effective-in-advanced-anal-cancer

Nivolumab Effective in Advanced Anal Cancer Treatment with the PD-1 inhibitor nivolumab (Opdivo) resulted in an overall response rate of 24.3% in previously treated patients with squamous cell carcinoma ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2949819825000494

Advances in anal cancer treatment: current standards, the ... From the 37 patients treated with nivolumab, 9 had radiographic responses (ORR 24%). Median PFS was 4.1 months, and median OS was 11.5 months.

5. opdivohcp.com opdivohcp.com/efficacy/crc

Efficacy Data for Colorectal Cancer (CRC) - Opdivo In Checkmate 9LA, the most common (>20%) adverse reactions were fatigue (49%), musculoskeletal pain (39%), nausea (32%), diarrhea (31%), rash (30%), decreased ...

6. news.bms.com news.bms.com/news/details/2025/U-S--Food-and-Drug-Administration-Approves-Opdivo-nivolumab-plus-Yervoy-ipilimumab-as-a-Treatment-for-Patients-with-Previously-Untreated-Microsatellite-Instability-High-or-Mismatch-Repair-Deficient-Unresectable-or-Metastatic-Colorectal-Cancer1/default.aspx

U.S. Food and Drug Administration Approves Opdivo ... In the CheckMate-8HW trial, Opdivo plus Yervoy demonstrated a 38% reduction in the risk of disease progression or death vs. Opdivo monotherapy ...

7. opdivo.com opdivo.com/clinical-trial-results

Clinical Trial Results Select your cancer type above to see how OPDIVO, alone or in combination with other therapies, performed in clinical trials.