Nivolumab for Anal Cancer

Recruiting at 1016 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

344 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug Nivolumab for anal cancer?

Nivolumab has shown effectiveness in treating other types of cancer, like advanced squamous non-small cell lung cancer, by improving survival rates and being better tolerated than some other treatments. Additionally, in anal cancer, the expression of PD-L1, which Nivolumab targets, is associated with better survival outcomes, suggesting potential effectiveness. ^{1 2 3 4 5}

Is Nivolumab generally safe for humans?

Nivolumab, also known as Opdivo, is generally considered safe for humans, but it can cause immune-related side effects like colitis (inflammation of the colon) and esophagitis (inflammation of the esophagus). In some studies, fewer patients experienced severe side effects with Nivolumab compared to other treatments, but it can still cause serious issues like pneumonitis (lung inflammation) and esophageal fistula (abnormal connection in the esophagus) in certain conditions. ^{6 7 8 9 10}

How does the drug nivolumab differ from other treatments for anal cancer?

Nivolumab is unique because it is a PD-1 inhibitor, which helps the immune system recognize and attack cancer cells, unlike traditional chemotherapy that directly targets cancer cells. This approach is novel for anal cancer, where standard treatments are limited. ^{1 5 11 12 13}

Research Team

Lakshmi Rajdev

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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

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

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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, 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]

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 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 (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]

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, 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 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. Ireland pubmed.ncbi.nlm.nih.gov

Anal carcinoma - Survival and recurrence in a large cohort of patients treated according to Nordic guidelines. [2022]

3. England pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

A clinical and molecular portrait of non-metastatic anal squamous cell carcinoma. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-Ligand 1 (PD-L1) Expression in Anal Cancer. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Severe Esophagitis and Gastritis from Nivolumab Therapy. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Adjuvant nivolumab for stage III/IV melanoma: evaluation of safety outcomes and association with recurrence-free survival. [2022]

8. United States 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. [2022]

9. England 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. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

Nivolumab-induced immune-mediated colitis: an ulcerative colitis look-alike-report of new cases and review of the literature. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023]

12. New Zealand pubmed.ncbi.nlm.nih.gov

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

13. England pubmed.ncbi.nlm.nih.gov

Nivolumab in NSCLC: latest evidence and clinical potential. [2022]