Cisplatin + Pembrolizumab for Head and Neck Cancer

Recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Trisha Wise-Draper

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Immunodeficiency, Metastatic disease, HPV+, 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

Compensation: Varies

Number of Visits: 13

96 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to test the safety and the benefit of adding pembrolizumab (a therapy that activates the immune system to fight cancer) to standard of care treatment for head and neck cancer. The standard of care treatment will include surgery followed by radiation for 6 weeks. Some patients may also receive cisplatin as standard of care once a week for 6 weeks if the cancer is found to be "high risk". High risk includes cancer that was not completely removed (positive margins) or cancer that has invaded through the outer lining of your lymph nodes.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you must stop these at least 7 days before starting the trial treatment.

What data supports the effectiveness of the treatment Cisplatin + Pembrolizumab for Head and Neck Cancer?

Research shows that adding cisplatin to radiation therapy improves outcomes for head and neck cancer compared to radiation alone. Pembrolizumab, used for recurrent or metastatic head and neck cancer, is effective as a first-line treatment. Combining pembrolizumab with radiotherapy has shown efficacy in locally advanced cases. ^{1 2 3 4 5}

Is the combination of Cisplatin and Pembrolizumab safe for treating head and neck cancer?

Pembrolizumab, when used with chemoradiation (a combination of chemotherapy and radiation therapy), has been shown to be safe and feasible for treating locally advanced head and neck cancer. However, specific safety data for the combination of Cisplatin and Pembrolizumab is not provided in the available research. ^{1 6 7 8 9}

How is the drug combination of Cisplatin and Pembrolizumab unique for treating head and neck cancer?

This treatment combines Cisplatin, a chemotherapy drug, with Pembrolizumab, an immune therapy that helps the body's immune system attack cancer cells, and radiation therapy. This combination is unique because it leverages the immune-stimulating effects of radiation to enhance the effectiveness of Pembrolizumab, potentially offering a new option for patients with locally advanced head and neck cancer who may not tolerate Cisplatin alone. ^{1 9 10 11 12}

Research Team

Trisha Wise-Draper, MD,PhD

Principal Investigator

University of Cincinnati

Eligibility Criteria

This trial is for adults with head and neck squamous cell carcinoma who are fit enough for surgery, have certain high-risk cancer features, and can handle standard treatments. They must not have immune deficiencies, be on recent immunosuppressants, or have specific other cancers or infections like TB or hepatitis.

Inclusion Criteria

I am willing to have surgery to remove a tumor and neck lymph nodes.

Adequate labs

I can carry out all my usual activities without help.

Exclusion Criteria

My throat cancer is caused by HPV.

I have an immune system disorder or have been on steroids or immune-suppressing drugs within the last week.

My cancer is located in the nasopharynx or sinonasal region.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo surgery as part of the standard of care treatment

1 week

1 visit (in-person)

Radiation

Participants receive radiation therapy for 6 weeks

6 weeks

6 visits (in-person, weekly)

Chemotherapy

High-risk participants receive cisplatin once a week for 6 weeks

6 weeks

6 visits (in-person, weekly)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Cisplatin
• Pembrolizumab
• Radiation Therapy
• Surgery

Trial Overview The study tests adding pembrolizumab to the usual care (surgery plus radiation) for head and neck cancer. Some patients may also get cisplatin if their cancer is 'high risk'. The goal is to see if pembrolizumab improves outcomes when combined with these standard therapies.

Participant Groups

Group I: Pembrolizumab Experimental Treatment 4 Interventions

Pembrolizumab in combination with standard of care surgery followed by radiation therapy with or without cisplatin

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Trisha Wise-Draper

Lead Sponsor

Trials

6

Recruited

230+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a phase II study involving 29 patients with locally advanced head and neck squamous cell carcinoma who were ineligible for cisplatin, the combination of pembrolizumab and radiotherapy showed promising efficacy, with a 24-month progression-free survival rate of 71%.

The treatment was generally well-tolerated, although a significant number of patients experienced grade 3/4 lymphopenia (58.6%), indicating the need for monitoring immune cell changes during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. Weiss, J., Sheth, S., Deal, AM., et al.[2023]

In a study comparing cisplatin and cetuximab added to radiation therapy for head and neck squamous cell carcinoma, patients receiving cisplatin had a significantly higher 3-year disease-specific survival rate of 83% compared to 31% for those receiving cetuximab.

Cisplatin treatment was associated with a lower recurrence rate of disease (4 patients) compared to cetuximab (17 patients), indicating that cisplatin may be more effective in improving outcomes when combined with radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin versus cetuximab given concurrently with definitive radiation therapy for locally advanced head and neck squamous cell carcinoma. Ley, J., Mehan, P., Wildes, TM., et al.[2021]

In a study of 4520 patients with stage III to IVb head and neck squamous cell carcinoma, those treated with cisplatin alongside radiation therapy had significantly better overall survival compared to those treated with cetuximab, with a median survival of 4.1 years versus 1.7 years for cetuximab.

After adjusting for treatment biases, cetuximab continued to show inferior overall survival rates, suggesting that cisplatin is a more effective partner for radiation therapy in the nonoperative management of this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin versus cetuximab with definitive concurrent radiotherapy for head and neck squamous cell carcinoma: An analysis of Veterans Health Affairs data. Bauml, JM., Vinnakota, R., Anna Park, YH., et al.[2023]

In a study of 646 adults with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), real-world outcomes showed that pembrolizumab, whether used alone or with chemotherapy, provided similar overall survival rates to those seen in clinical trials, with median overall survival of 12.1 months for monotherapy and 11.9 months for combination therapy.

Factors such as HPV-positive tumor status and lower Eastern Cooperative Oncology Group performance status were associated with longer overall survival, highlighting the importance of tumor characteristics in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world treatment patterns and outcomes among individuals receiving first-line pembrolizumab therapy for recurrent/metastatic head and neck squamous cell carcinoma. Black, CM., Hanna, GJ., Wang, L., et al.[2023]

In a study of 1,149 patients with advanced head and neck squamous cell carcinoma, carboplatin-based chemoradiotherapy showed similar cancer-specific mortality rates compared to cisplatin-based therapy, indicating that carboplatin can be an effective alternative for patients unable to receive cisplatin.

Both carboplatin and cisplatin-based chemoradiotherapy were found to be more effective than radiation therapy alone or radiation with cetuximab, suggesting that carboplatin should be further investigated as a viable treatment option for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival After Definitive Chemoradiotherapy With Concurrent Cisplatin or Carboplatin for Head and Neck Cancer. Xiang, M., Colevas, AD., Holsinger, FC., et al.[2020]

Pemetrexed shows promising efficacy as a treatment for head and neck cancer, particularly when used in combination with other chemotherapeutic agents or radiotherapy, based on a review of ten studies.

The drug has an acceptable safety profile, with fewer severe nonhematologic toxicities compared to cisplatin, making it a potential alternative worth further investigation, especially as a radiosensitizer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in head and neck cancer: a systematic review. Argiris, A., Pennella, E., Koustenis, A., et al.[2018]

In a study of 167 patients with recurrent/metastatic squamous cell carcinoma of the head and neck treated with pembrolizumab, the median overall survival was 22.7 months and progression-free survival was 5.1 months for those receiving pembrolizumab alone, indicating significant efficacy.

The presence of immune-related adverse events (irAEs) was associated with better progression-free survival, suggesting that these side effects may serve as important prognostic factors in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. Okada, T., Fushimi, C., Matsuki, T., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

The Phase III trial KEYNOTE-412 is designed to evaluate the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, when used alongside chemoradiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Previous Phase Ib studies have indicated that combining pembrolizumab with CRT is safe and feasible, supporting its potential use in this larger trial to improve treatment outcomes for patients with locally advanced HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Machiels, JP., Tao, Y., Burtness, B., et al.[2021]

In a phase IB study involving 59 patients with locally advanced head and neck squamous cell carcinoma, the combination of pembrolizumab with cisplatin-based chemoradiotherapy was found to be safe, with a high completion rate of treatment and only 8.8% of patients experiencing immune-related adverse events.

The treatment showed promising efficacy, with complete response rates of 85.3% for HPV-positive and 78.3% for HPV-negative patients, suggesting that this combination warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. Powell, SF., Gold, KA., Gitau, MM., et al.[2022]

The study evaluated the effectiveness of pembrolizumab and cetuximab, both alone and in combination, on head and neck squamous cell carcinoma (HNSCC) using the FLAVINO assay, revealing significant variability in patient responses, particularly in those with cisplatin-resistant cases.

An 'IP-10 score' was developed to predict patient outcomes based on their response to treatment, indicating that higher levels of IP-10 release in response to interferon gamma (IFN-γ) stimulation may correlate with better outcomes for certain HNSCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker. Berszin, M., Michaelides, I., Siemert, J., et al.[2022]

References

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

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Cisplatin versus cetuximab given concurrently with definitive radiation therapy for locally advanced head and neck squamous cell carcinoma. [2021]

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

Cisplatin versus cetuximab with definitive concurrent radiotherapy for head and neck squamous cell carcinoma: An analysis of Veterans Health Affairs data. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Real-world treatment patterns and outcomes among individuals receiving first-line pembrolizumab therapy for recurrent/metastatic head and neck squamous cell carcinoma. [2023]

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

Survival After Definitive Chemoradiotherapy With Concurrent Cisplatin or Carboplatin for Head and Neck Cancer. [2020]

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

Pemetrexed in head and neck cancer: a systematic review. [2018]

7. Greece pubmed.ncbi.nlm.nih.gov

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]

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

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. [2021]

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

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker. [2022]

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

Survival of patients with head and neck cancer treated with definitive radiotherapy and concurrent cisplatin or concurrent cetuximab: A Surveillance, Epidemiology, and End Results-Medicare analysis. [2019]