Immunoradiotherapy for Head and Neck Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Providence Health & Services

Must not be taking: Oral steroids

Disqualifiers: Active infection, Autoimmune diseases, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

22 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic oral steroids at a dose of 20mg or more of prednisone daily, you may not be eligible to participate.

What data supports the effectiveness of the treatment for head and neck cancer?

Research shows that drugs like Nivolumab and Pembrolizumab, which are part of the treatment, have been effective in treating head and neck cancers, especially when combined with other therapies like surgery or radiation. These drugs help the immune system fight cancer cells and have shown promise in improving outcomes for patients with advanced stages of the disease. ^{1 2 3 4 5}

Is immunoradiotherapy for head and neck cancer safe for humans?

Immunotherapy drugs like pembrolizumab (Keytruda) and nivolumab (Opdivo) have been used safely in humans for head and neck cancer, though they can cause side effects like pneumonia, skin issues, and thyroid problems. Studies show these treatments are generally safe, with no unexpected severe immune-related side effects reported. ^{2 6 7 8 9}

How is the drug Keytruda different from other treatments for head and neck cancer?

Keytruda (pembrolizumab) is unique because it is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells, and it can be used in combination with radiation therapy to enhance the immune response against tumors. This approach is particularly beneficial for patients who cannot tolerate standard chemotherapy, like cisplatin, and offers a novel way to treat locally advanced head and neck cancer. ^{1 2 10 11 12}

What is the purpose of this trial?

The purpose of this study is to test the safety of neoadjuvant immunoradiotherapy as a safe means of down-staging Head and Neck Squamous Cell Carcinoma (HNSCC) prior to surgical resection.

Research Team

Rom Leidner, MD

Principal Investigator

Providence Health and Services

Eligibility Criteria

Adults with head and neck squamous cell carcinoma scheduled for surgery can join. They must have certain blood counts, be HPV status known, able to consent, and have an acceptable performance status. Pregnant women or those not using contraception are excluded, as well as individuals on high-dose steroids or with active autoimmune diseases.

Inclusion Criteria

My cancer's HPV status has been checked.

Patients with history of psychiatric illness judged by the investigator as able to understand the investigational nature and risks associated with the therapy

Laboratory values within specified ranges

Exclusion Criteria

I take 20mg or more of prednisone or its equivalent daily.

History of or current active autoimmune disease posing an active and significant morbidity risk

Clinical factors such as bleeding, active infection, or psychiatric factors that would preclude safe participation and compliance with study procedures

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Immunoradiotherapy

Participants receive nivolumab and radiation therapy prior to surgical resection to assess safety and feasibility

6 weeks

Multiple visits for treatment administration

Surgical Resection

Participants undergo surgical resection of tumors following neoadjuvant therapy

1 week

1 visit (in-person)

Adjuvant Therapy

Participants receive additional nivolumab doses and risk-adapted adjuvant therapy as per standard of care

12 weeks

6 visits (in-person, every 4 weeks)

Follow-up

Participants are monitored for disease-free and overall survival

5 years

Treatment Details

Interventions

• Nivolumab
• Radiation (3 days)
• Radiation (5 days)
• Surgical Resection

Trial Overview The trial is testing if giving Nivolumab (an immunotherapy drug) combined with a short course of radiation before surgery can safely shrink tumors in patients with head and neck cancer. The study will separate participants into groups based on their HPV status.

Participant Groups

Group I: Treatment Cohort 4 Experimental Treatment 3 Interventions

Nivolumab administration (3 doses) and radiation (3 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses).

Group II: Treatment Cohort 3 Experimental Treatment 3 Interventions

Radiation (3 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses).

Group III: Treatment Cohort 2 Experimental Treatment 3 Interventions

Nivolumab administration (3 doses) and radiation (3 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses).

Group IV: Treatment Cohort 1 Experimental Treatment 3 Interventions

Nivolumab administration (3 doses) and radiation (5 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses).

Surgical Resection is already approved in United States, European Union for the following indications:

Approved in United States as Keytruda for:

• Melanoma
• Non-small cell lung cancer
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Endometrial carcinoma
• Esophageal carcinoma
• Gastric cancer

Approved in European Union as Keytruda for:

• Melanoma
• Non-small cell lung cancer
• Urothelial carcinoma
• Head and neck squamous cell carcinoma
• Renal cell carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Endometrial carcinoma
• Esophageal carcinoma
• Gastric cancer

Who Is Running the Clinical Trial?

Providence Health & Services

Lead Sponsor

Trials

131

Recruited

827,000+

Providence Cancer Center, Earle A. Chiles Research Institute

Collaborator

Trials

21

Recruited

500+

Findings from Research

In a study of 22 patients with resectable locally advanced head and neck squamous cell carcinomas, the combination of pembrolizumab and chemotherapy resulted in a postoperative pathological complete response (pCR) rate of 36.4%, indicating significant efficacy as a neoadjuvant treatment.

The treatment did not adversely affect surgical safety, with a high rate of laryngeal function preservation at 90.9%, and no delays to surgery due to adverse drug reactions, although delayed wound healing was noted in 22.7% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab with preoperative neoadjuvant chemotherapy in patients with resectable locally advanced head and neck squamous cell carcinomas. Wang, K., Gui, L., Lu, H., et al.[2023]

In a study of platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas involving 36 patients, both nivolumab and pembrolizumab showed effectiveness, with median overall survival of 16.9 months for nivolumab and 19.2 months for pembrolizumab, indicating similar efficacy between the two treatments.

The median progression-free survival was 4.8 months for nivolumab and 9.3 months for pembrolizumab, with objective response rates of 38% and 47%, respectively, suggesting that both drugs are viable options for treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Yamashita, G., Okamoto, I., Ito, T., et al.[2023]

The combination of stereotactic body radiation therapy (SBRT) with the anti-PD-1 drug nivolumab was found to be safe and did not delay surgery in 21 patients with advanced head and neck cancer, meeting the primary safety endpoint of the study.

This treatment approach resulted in a high major pathological response (mPR) rate of 86% and a pathological complete response (pCR) rate of 67%, indicating that adding SBRT may enhance the effectiveness of immunotherapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant immunoradiotherapy results in high rate of complete pathological response and clinical to pathological downstaging in locally advanced head and neck squamous cell carcinoma. Leidner, R., Crittenden, M., Young, K., et al.[2022]

Neoadjuvant immunotherapy targeting the PD-1/PD-L1 axis in head and neck cancer has shown a favorable overall objective response rate of 45.9% across eight clinical trials involving 260 patients.

Importantly, there were no deaths reported due to immune-related toxicities, indicating that this treatment approach is not only effective but also safe in the neoadjuvant setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant immunotherapy prior to surgery for mucosal head and neck squamous cell carcinoma: Systematic review. Amin, N., Maroun, CA., El Asmar, M., et al.[2022]

In a study of patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with nivolumab, the median overall survival was 9.6 months, with a two-year survival rate of 25%, indicating long-term efficacy in a real-world setting.

The study found that better overall response rates (18% overall response, 48% disease control) and the occurrence of immune-related adverse events (irAEs) were associated with improved survival outcomes, suggesting these factors could serve as important markers for patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World, Long-Term Outcomes of Nivolumab Therapy for Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck and Impact of the Magnitude of Best Overall Response: A Retrospective Multicenter Study of 88 Patients. Matsuki, T., Okamoto, I., Fushimi, C., et al.[2020]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

Immunotherapy, specifically pembrolizumab and nivolumab, has been FDA approved since 2016 for treating recurrent/metastatic head and neck squamous cell carcinoma, showing significant effectiveness in patients who have not responded to platinum-based treatments.

Advanced practice providers play a crucial role in managing immune-related adverse events (irAEs) associated with these immunotherapies, and the Care Step Pathways (CSPs) developed for this purpose help in diagnosing and managing conditions like thyroiditis and skin toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Checkpoint Inhibitor Immunotherapy for Head and Neck Cancer: Incorporating Care Step Pathways for Effective Side-Effect Management. Fazer, C.[2020]

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 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]

References

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

Phase II Trial of Adjuvant Nivolumab Following Salvage Resection in Patients with Recurrent Squamous Cell Carcinoma of the Head and Neck. [2023]

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

Efficacy and safety of pembrolizumab with preoperative neoadjuvant chemotherapy in patients with resectable locally advanced head and neck squamous cell carcinomas. [2023]

3. Greece pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. [2023]

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

Neoadjuvant immunoradiotherapy results in high rate of complete pathological response and clinical to pathological downstaging in locally advanced head and neck squamous cell carcinoma. [2022]

5. Greece pubmed.ncbi.nlm.nih.gov

Real-world Experience With Pembrolizumab for Advanced-stage Head and Neck Cancer Patients: A Retrospective, Multicenter Study. [2022]

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

Neoadjuvant immunotherapy prior to surgery for mucosal head and neck squamous cell carcinoma: Systematic review. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World, Long-Term Outcomes of Nivolumab Therapy for Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck and Impact of the Magnitude of Best Overall Response: A Retrospective Multicenter Study of 88 Patients. [2020]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. [2019]

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

Checkpoint Inhibitor Immunotherapy for Head and Neck Cancer: Incorporating Care Step Pathways for Effective Side-Effect Management. [2020]

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

Immune checkpoint expression in HNSCC patients before and after definitive chemoradiotherapy. [2021]

11. 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]

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

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