Nivolumab for Advanced Cervical Cancer

Recruiting at 364 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, Brain metastases, HIV, others

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

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: 5

Duration: 92 weeks

26 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial requires that any prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted agents, and immunologic agents, must be stopped at least three weeks before joining. Investigational agents must be stopped for at least 30 days before joining. The protocol does not specify other medications, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Nivolumab for advanced cervical cancer?

Research shows that Nivolumab, an immune checkpoint inhibitor, had a disease control rate of 68.4% in a phase II study for advanced cervical cancer. Additionally, a separate study found that Nivolumab had an objective response rate of 25% in patients with cervical cancer, with better responses in those with PD-L1-positive tumors. ^{1 2 3 4 5}

Is nivolumab safe for treating advanced cervical cancer?

Nivolumab has been studied for safety in patients with advanced cervical cancer, showing acceptable toxicity levels. Some patients experienced immune-related side effects, but these were managed successfully. ^{3 4 5 6 7}

How is the drug Nivolumab unique in treating advanced cervical cancer?

Nivolumab is unique because it is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells, offering a new option for patients with advanced cervical cancer who have limited treatment choices after standard therapies. It works by blocking the PD-1/PD-L1 pathway, which cancer cells use to hide from the immune system, and has shown promising results in clinical trials for patients with recurrent or metastatic cervical cancer. ^{3 4 5 8 9}

What is the purpose of this trial?

This phase II trial studies the side effects and how well nivolumab works in treating patients with cervical cancer that has grown, come back, or spread to other places in the body. Monoclonal antibodies, such as nivolumab, may block tumor growth in different ways by targeting certain cells.

Research Team

Alessandro D Santin

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for patients with persistent, recurrent, or metastatic cervical cancer. Participants must have completed prior treatments and recovered from their effects, have measurable disease as per RECIST 1.1 criteria, and a performance status of 0 or 1. They should not be pregnant or nursing and agree to use contraception. Exclusions include brain metastases under certain conditions, HIV/AIDS, active hepatitis infection, autoimmune diseases requiring treatment, previous nivolumab therapy or similar drugs targeting immune pathways.

Inclusion Criteria

You must have had a scan of the specific area being treated within the past 28 days before enrolling in the trial.

I stopped any cancer treatments at least 3 weeks ago.

I haven't taken any experimental drugs in the last 30 days.

Exclusion Criteria

I do not have current severe digestive system problems.

I have previously been treated with specific immune-targeting cancer drugs.

I do not have any severe illnesses or social situations that would prevent me from following the study's requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab intravenously every 2 weeks for a maximum of 46 doses over 92 weeks

92 weeks

Every 2 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

Every 3 months for 2 years, then every 6 months for 3 years

Treatment Details

Interventions

• Nivolumab

Trial Overview The trial is testing the effectiveness of Nivolumab—a monoclonal antibody—in treating cervical cancer that has grown back or spread. It aims to see how well it works by blocking tumor growth in different ways by targeting specific cells.

Participant Groups

Group I: Treatment (nivolumab) Experimental Treatment 2 Interventions

Patients receive nivolumab IV over approximately 60 minutes every 2 weeks for a maximum of 46 doses over 92 weeks in the absence of disease progression or unacceptable toxicity.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Findings from Research

In a study of 4 patients with advanced cervical cancer treated with pembrolizumab, all patients tolerated the treatment well, with one patient achieving a remarkable 21-month progression-free survival, indicating potential efficacy of this PD-1 inhibitor.

Biomarker analysis revealed that patients with a combined positive score (CPS) for PD-L1 of ≥1 and specific somatic mutations, such as in PIK3CA, may benefit from pembrolizumab, suggesting that further research into predictive biomarkers could enhance patient selection for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor molecular profiling of responders and non-responders following pembrolizumab monotherapy in chemotherapy resistant advanced cervical cancer. Ngoi, NYL., Heong, V., Lee, XW., et al.[2020]

Pembrolizumab is an FDA-approved immune checkpoint inhibitor specifically targeting the PD-1 receptor, showing promise in treating recurrent or metastatic cervical cancer in patients whose tumors express PD-L1.

Clinical studies suggest that pembrolizumab could become a preferred treatment option for advanced cervical cancer, but further research is needed to identify which patients will benefit the most from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for advanced cervical cancer: safety and efficacy. De Felice, F., Giudice, E., Bolomini, G., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Tumor molecular profiling of responders and non-responders following pembrolizumab monotherapy in chemotherapy resistant advanced cervical cancer. [2020]

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

Phase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002). [2021]

4. England pubmed.ncbi.nlm.nih.gov

Nivolumab in chemotherapy-resistant cervical cancer: report of a vulvitis as a novel immune-related adverse event and molecular analysis of a persistent complete response. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nivolumab in Japanese patients with uterine cervical cancer, uterine corpus cancer, or soft tissue sarcoma: Multicenter, open-label phase 2 trial. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Nivolumab plus chemoradiotherapy in locally-advanced cervical cancer: the NICOL phase 1 trial. [2023]

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

Pembrolizumab for advanced cervical cancer: safety and efficacy. [2021]

8. Mexico pubmed.ncbi.nlm.nih.gov

IMMUNOTHERAPY TREATMENT AGAINST CERVICAL CANCER. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Advances in immunotherapy for cervical cancer: recent developments and future directions. [2022]