Phase II Trial of Adjuvant Cisplatin and Radiation With Pembrolizumab in Resected Head and Neck Squamous Cell Carcinoma

Study Overview
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Brief Summary
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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.

Official Title
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Phase II Investigation of Adjuvant Combined Cisplatin and Radiation With Pembrolizumab in Resected Head and Neck Squamous Cell Carcinoma

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: Pembrolizumab
* Procedure: Surgery
* Radiation: Radiation Therapy
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients eligible for resection with one or more of the following Any T stage with ≥ N2 disease; T4 disease, any N stage; T3 Oral Cavity, any N stage; or Clinical evidence of extra-capsular extension on scans. Must be willing to undergo definitive resection with neck dissection. Performance status 0 or 1 on Eastern Cooperative Oncology Group Performance Scale. Adequate labs Appropriate staging imaging. Exclusion Criteria: Diagnosis of immunodeficiency or receiving systemic steroid therapy or immunosuppressive therapy within 7 days prior to planned first dose of trial treatment. Nasopharyngeal or sinonasal carcinoma Confirmed metastatic disease Human Papillomavirus (HPV)+ disease of the oropharynx Known history of active tuberculosis (TB), autoimmune disease, pneumonitis, infection, HIV, Hepatitis B, or Hepatitis C

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab<br>Pembrolizumab in combination with standard of care surgery followed by radiation therapy with or without cisplatin | Drug: Pembrolizumab<br>* Pembrolizumab administered one week prior to surgery and then every three weeks in the adjuvant setting for a total of 7 doses.<br>* Other names: Keytruda;Procedure: Surgery<br>* gross total surgical resection<br>Radiation: Radiation Therapy<br>* 60-66 Gy over 6 weeks<br>Drug: Cisplatin<br>* Weekly during radiation therapy for 6 doses only for patients with high risk pathological features<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Related Adverse Effects | Number of participants with treatment related adverse effects as assessed using CTCAE v4.0 of pembrolizumab when combined with radiation alone and chemoradiation. Compared as percentage of grade 3 and 4 adverse events with historical control percentages. | All adverse events were recorded from the time the consent form is signed through 30 days following cessation of treatment. Any AE related to study drug after 30 days post treatment, subjects were followed until resolution. | 
| Disease Free Survival in Resected High Risk Patients Treated With Adjuvant Pembrolizumab and Chemoradiation | • High risk is defined as those with biopsies that have the following features: extracapsular spread or those with positive surgical margins. | 1 year | 
| Disease Free Survival in Resected Intermediate Risk Patients Treated With Adjuvant Pembrolizumab and Radiation | • Intermediate risk is defined as those with biopsies that do not have the following features: extracapsular spread or those with positive surgical margins. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Immune Response to Pembrolizumab as Defined by PD-L1 CPS in the Baseline Tumor Tissue | Change in distribution of the tumor immune microenvironment after Pembrolizumab administration in tumor biopsy tissue using markers of T cells and T cell activation using PD-L1 CPS. PD-L1 CPS is defined as the PD-L1 combined positive score. PD-L1 CPS is defined as Combined positivity score (CPS) was calculated by summing the numbers of PD-L1-positive tumor cells and immune cells and dividing by the total number of viable tumor cells. Additionally, PD-L1 is a protein that helps the body immune system remain in control. The denominator in this case is 72 subjects that were evaluable. Evaluable means the subject had a pre-surgery pembrolizumab and a biopsy taken. The numerators are explained below. | 1 week between receiving a pre-surgery dose of pembrolizumab and surgery when the biopsy was taken | 
| Overall Survival in Resected Intermediate Risk Patients Treated With Adjuvant Pembrolizumab and Radiation | • Intermediate risk is defined as those with biopsies that do not have the following features: extracapsular spread or those with positive surgical margins | 1 year | 
| Overall Survival in Resected High Risk Patients Treated With Adjuvant Pembrolizumab and Chemoradiation | • High risk is defined as those with biopsies that have the following features: extracapsular spread or those with positive surgical margins. | 1 year |