Immunotherapy for Head and Neck Cancer

Not currently recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Immunosuppressants, Steroids, Live vaccines, others

Disqualifiers: HPV-positive, Metastatic, Immunodeficiency, 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new immunotherapy treatment, MK-3475 (pembrolizumab), to determine if it can reduce the risk of cancer recurrence or spread in individuals with advanced head and neck cancer. Participants will receive this treatment alongside standard care, which includes surgery, chemotherapy (cisplatin), and radiation. The trial seeks individuals with untreated advanced head and neck cancer, excluding those with HPV-related cancers or specific types of sinus cancer. This trial might be suitable for those considering new treatment options. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, providing an opportunity to explore promising new therapies.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive drugs, you may need to stop them before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pembrolizumab (also known as MK-3475) has been studied for treating head and neck cancers. One study found it helped patients when used both before and after surgery. However, further research is needed to fully understand its safety for Head and Neck Squamous Cell Carcinoma (HNSCC). Pembrolizumab is approved in regions like Europe for similar conditions, suggesting a safety record worth considering.

For cisplatin, studies indicate that different dosing schedules (weekly or every three weeks) have similar safety outcomes. It is often used for head and neck cancers, with most side effects known and manageable. However, serious side effects, such as kidney problems, can occur, which doctors will monitor closely.

Overall, these treatments have been used in various studies and other conditions, providing some insight into their safety, but individual responses can vary. Participants should discuss any concerns with their healthcare providers to understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about MK-3475, also known as pembrolizumab, because it offers a different approach from traditional treatments for head and neck cancer, which typically include surgery, chemotherapy (like cisplatin), and radiation therapy. Unlike these standard options, pembrolizumab is an immunotherapy drug that works by blocking the PD-1 pathway, which can help the immune system recognize and attack cancer cells more effectively. This mechanism of action is unique because it empowers the body's natural defenses rather than directly targeting the cancer cells with chemicals or radiation. Additionally, pembrolizumab is administered intravenously, providing a systemic treatment that can potentially address cancer cells throughout the body. This innovative approach has researchers hopeful for improved outcomes in patients, especially those at high risk.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research has shown that pembrolizumab (MK-3475), one of the treatments in this trial, may effectively treat head and neck squamous cell cancers (HNSCC). Studies have found that pembrolizumab can extend the lives of patients with these cancers. For instance, one study reported that 73% of patients were alive after five years, and 71% experienced no cancer-related events. Another study demonstrated that adding pembrolizumab to standard treatment significantly improved survival rates for patients with locally advanced cancer. These findings suggest that pembrolizumab could be a strong option in fighting HNSCC. ^{6 7 8 9 10}

Who Is on the Research Team?

Douglas R. Adkins

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Adults with stage III or IV head and neck squamous cell carcinoma (excluding HPV-positive types) who are fit for surgery, have not had prior treatment for this cancer, and meet certain health criteria like normal organ function. Participants must be willing to use two forms of contraception during the study.

Inclusion Criteria

Measurable disease defined as lesions that can be accurately measured in at least one dimension

My cancer is in the mouth, throat, or voice box and is not related to HPV.

I am fully active and can carry on all pre-disease activities without restriction.

Exclusion Criteria

I do not have any unmanaged ongoing illnesses.

A history of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-3475 or other agents used in the study

I have received treatment for head and neck cancer before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

MK-3475 is administered intravenously once approximately 2-3 weeks prior to standard of care surgery

2-3 weeks

Surgery

Standard of care surgery is performed

1 day

Adjuvant Treatment

Adjuvant therapy including risk-based radiation and chemotherapy, and MK-3475 administered every 3 weeks for up to 6 doses

18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Image-guided radiation therapy
• Intensity modulated radiation therapy
• MK-3475
• Peripheral blood
• Surgery

Trial Overview The trial is testing MK-3475 (pembrolizumab), given before and after surgery, along with standard treatments including radiation therapy and cisplatin chemotherapy. The aim is to see if pembrolizumab can reduce the risk of cancer returning or spreading in high-risk patients.

How Is the Trial Designed?

Group I: Cohort 2: Neoadjuvant MK-3475 Experimental Treatment 6 Interventions

-MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery)

Group II: Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 Experimental Treatment 7 Interventions

* MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery. * Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of: * risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions) * optional image-guided radiation therapy * risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course * MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based surgical pathology from standard of care surgery. These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less.

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?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

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

Published Research Related to This Trial

In a phase I-II study involving 12 patients with unresectable head and neck squamous cell carcinomas, the combination of radiation and cisplatin (CDDP) resulted in a complete response in 66% of patients, with some remaining disease-free for up to 34 months after treatment.

The recommended dose of CDDP was determined to be 6 mg/m2/day, with manageable side effects; notably, mucositis severity was similar to that of radiation alone, and there was no significant nephro-, oto-, or neurotoxicity observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy with concomitant continuous cisplatin infusion for unresectable tumors of the upper aerodigestive tract: results of a phase I study. Bachaud, JM., Chatelut, E., Canal, P., et al.[2019]

In a study of 181 patients with locally advanced head and neck cancers, nimotuzumab-based concurrent chemoradiotherapy resulted in the least hematological toxicities compared to cisplatin, nedaplatin, and lobaplatin.

Lobaplatin was associated with a higher incidence of severe leukopenia (48.5%) and thrombocytopenia compared to cisplatin, indicating that while some alternatives to cisplatin may reduce gastrointestinal and nephrotoxicity, they can still pose significant hematological risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematological Toxicities of Concurrent Chemoradiotherapies in Head and Neck Cancers: Comparison Among Cisplatin, Nedaplatin, Lobaplatin, and Nimotuzumab. Wu, Q., Zhu, C., Zhang, S., et al.[2022]

In a study of 60 patients with locally advanced head and neck squamous cell carcinoma (HNSCC), weekly low-dose cisplatin (30 mg/m2) resulted in significantly lower acute toxicities compared to high-dose cisplatin (100 mg/m2 every 3 weeks), with 56.6% of patients experiencing severe side effects versus 76.6% in the high-dose group.

While the low-dose regimen had better patient compliance (70% completing at least 6 doses) and lower toxicity, it also resulted in a lower loco-regional control rate (57.6%) compared to the high-dose group (72.8%), indicating a trade-off between safety and treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin Weekly Versus Every 3 Weeks Concurrently with Radiotherapy in the Treatment of Locally Advanced Head and Neck Squamous Cell Carcinomas: What Is the Best Dosing and Schedule? Mashhour, K., Hashem, W.[2020]

In a study of 82 advanced head and neck cancer patients undergoing concurrent chemoradiotherapy with high-dose cisplatin, 26% experienced renal impairment, highlighting the need for careful monitoring of kidney function during treatment.

Risk factors for cisplatin-induced renal impairment included the use of calcium channel blockers and lower hemoglobin levels, while the use of proton pump inhibitors was associated with a reduced risk, suggesting potential strategies to enhance patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Risk Factors for High-dose Cisplatin-induced Renal Impairment in Head and Neck Cancer Patients. Koide, H., Noda, S., Okunuki, Y., et al.[2022]

In a study of 89 head and neck cancer patients treated with cisplatin, 29% experienced moderate to severe hearing loss, particularly at higher frequencies, indicating significant ototoxicity associated with this chemotherapy.

Specific genetic variants related to drug metabolism and DNA repair were found to increase the risk of ototoxicity, with some patients having up to 32 times higher odds of severe hearing loss, suggesting these genetic markers could help predict who is at greater risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Clinical Aspects and Genetic Variants with the Severity of Cisplatin-Induced Ototoxicity in Head and Neck Squamous Cell Carcinoma: A Prospective Cohort Study. Macedo, LT., Costa, EFD., Carvalho, BF., et al.[2023]

In a pilot study involving three patients with advanced head and neck cancer, the combination of radiation therapy and cisplatin (CDDP) resulted in severe side effects, including abscesses and significant nausea and vomiting.

The observed toxicities were greater than expected from either treatment alone, raising concerns about the safety of using this combination in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant radiation therapy and cis-diamminedichloroplatinum (II) in patients with advanced head and neck cancer. Creagan, ET., Fountain, KS., Frytak, S., et al.[2019]

Combined modality treatment using cisplatin and radiotherapy for head and neck cancer shows promising results in local control and survival rates, leading to the initiation of three Phase III trials for advanced stages of various cancers in this region.

While the combination treatment can increase mucosal toxicity and myelosuppression, it does not hinder the delivery of standard radiotherapy, suggesting that patient compliance can be managed effectively during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin and radiotherapy in the management of locally advanced head and neck cancer. Forastiere, AA.[2019]

In a phase I study involving 12 patients with locoregionally advanced head and neck cancer, the combination of low-dose cisplatin and docetaxel with radiotherapy showed promising efficacy, with complete response rates ranging from 33% to 67% across different docetaxel dose levels.

The treatment was generally well-tolerated, with minimal hematological toxicities and no grade 4 toxicities, although grade 3 mucositis was common, indicating that while effective, careful monitoring of side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiotherapy with cisplatin and docetaxel for advanced head and neck cancer. A phase I study. Inohara, H., Inoue, T., Akahani, S., et al.[2018]

The addition of low-dose cisplatin (CDDP) to hyperfractionated radiation therapy (Hfx RT) significantly improved survival rates in patients with locally advanced squamous cell carcinoma of the head and neck, with 68% survival at 2 years compared to 49% with Hfx RT alone.

Despite the survival benefits, the combination treatment did not increase the incidence of severe radiation-induced toxicity compared to Hfx RT alone, although higher rates of hematologic toxicity were observed in patients receiving CDDP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. Jeremic, B., Shibamoto, Y., Milicic, B., et al.[2022]

In a study involving 17 patients with head and neck squamous cell carcinoma, treatment with cis-diamminedichloroplatinum (CDDP) at a dose of 2.5 mg/kg resulted in one complete response and five partial responses, indicating its potential efficacy as a treatment.

The treatment was associated with only moderate toxicity, suggesting that CDDP may be a relatively safe option for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cis-disamminedichloroplatinum (II) CDDP: single agent in the treatment of advanced head and neck squamous cell carcinoma. Tranter, RM., Howell, A.[2019]

Carboplatin-based chemoradiation therapy (CTRT) is a well-tolerated alternative for patients with locally advanced head and neck cancers who are unfit for cisplatin, with 84.1% of patients completing the planned treatment.

The study found a median overall survival of 28 months and progression-free survival of 17 months, suggesting that carboplatin-based CTRT may offer better outcomes compared to radical radiotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin-based concurrent chemoradiation therapy in locally advanced head and neck cancer patients who are unfit for cisplatin therapy. Noronha, V., Sharma, V., Joshi, A., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11694497/

Real-World Evidence on the Effectiveness of Pembrolizumab ... The study showed some beneficial effects of pembrolizumab monotherapy in recurrent/metastatic/unresectable HNSCC patients in real-world scenarios.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6079

5-year survival outcomes after perioperative ... The 5-year OS for all patients was 73% (95% CI: 62-85%) and the EFS was 71% (95% CI: 61-83%). A comparison of patients ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02252042

Study Details | NCT02252042 | Pembrolizumab (MK-3475) ... These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2415434

Neoadjuvant and Adjuvant Pembrolizumab in Locally ... The addition of neoadjuvant and adjuvant pembrolizumab to standard care significantly improved event-free survival among participants with locally advanced ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804925001765

5-year follow-up from the randomized phase III KEYNOTE- ... Previous results of the phase 3 KEYNOTE-048 study showed that pembrolizumab significantly improved overall survival (OS) compared with cetuximab ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2772906025000263

Review Article Comparing efficacy and safety of weekly vs. ... Both weekly and triweekly cisplatin regimens show comparable survival outcomes and safety profiles in patients with head and neck cancers, except for short term ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9875652/

Treatment outcomes of standard (high dose) cisplatin and non ... Safety data included rates of grade 3 or higher treatment‐related adverse events (TRAEs), as per common terminology criteria for adverse events ...

8. nrgoncology.org nrgoncology.org/HN009

NRG-HN009: Cisplatin and Radiation for Advanced Head ... This study compares two schedules of the chemotherapy drug, cisplatin, given every three weeks versus every week with radiation for patients with this type of ...

9. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2827612

Weekly Cisplatin Cycles and Outcomes for Chemoradiation ... These findings suggest that missing several cycles of weekly cisplatin is associated with worse survival, even among those with p16-negative tumors.

10. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-021-01966-4

safety propensity score analysis on 166 head and neck cancer ... Three weekly versus weekly concurrent cisplatin: safety propensity score analysis on 166 head and neck cancer patients.