A Study of Chemoradiation Plus Pembrolizumab for Locally Advanced Laryngeal 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 larynx cancer. The standard of care treatment will include chemotherapy and radiation for 7 weeks.

Detailed Description
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This study is an open label, single arm study which will enroll patients with locally advanced squamous cell carcinomas of the larynx. Positive tumor PDL1 expression by IHC will not be required for enrollment. All patients with receive Pembrolizumab and cisplatin in combination with radiation. Pembrolizumab 200 mg flat dose given Q21 days will begin 3 weeks prior to initiation of chemoradiation and continued through the 21-day cycle until completion of chemoradiation. Cisplatin will be given 100 mg/m2 every 21 days during radiation as per standard of care. Pembrolizumab has well defined toxicities as single agent and has non-overlapping mechanisms of action with cisplatin and radiation. The safety of these agents used in combination has not been previously described, therefore the study will begin with a safety run-in phase 1 followed by the phase II design. See statistical section for details.

Official Title
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A Phase I/II Study of Chemo Radiation Plus the Anti-Programmed Death-1 (Anti-PD-1) Antibody, Pembrolizumab (MK-3475) for Locally Advanced Laryngeal Squamous Cell Carcinoma

Conditions
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Head and Neck Cancer

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy-proven, previously untreated stage III or IV squamous cell carcinoma of the larynx, Primary tumor stage (T2, T3) and nodal stage (N0, N1, N2, N3). Measurable disease based on RECIST 1.1. Performance status 0 or 1 on Eastern Cooperative Oncology Group Performance Scale. Anticipated survival minimum of 12 months. Adequate labs Exclusion Criteria: Patients with T1 primary tumor or T4 large volume tumor that has resulted in larynx dysfunction at baseline (for example tumor largely penetrating into base of tongue and resulting in inability to swallow at baseline) Prior radiation therapy to the larynx area or involved neck. Distant metastasis 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 every 3 weeks in combination with 7 weeks of radiation therapy and every 3 week cisplatin | Drug: Pembrolizumab<br>* 200mg every 3 weeks starting 3 weeks prior to chemoradiotherapy. Maximum of 4 doses<br>* Other names: Keytruda;Radiation: Radiation Therapy<br>* 70 Gy in 35 fractions over 7 weeks<br>Drug: Cisplatin<br>* 100 mg/m2 every 3 weeks starting on day 1 of chemoradiotherapy. Maximum of 3 doses.<br>* Other names: Platinol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Related Grade 3 or 4 Adverse Events as Assessed by CTCAE V4.0 | Greater than 2 grade 3 or 4 adverse events that are definitely, probably or possibly related to the pembrolizumab in the first cohort of 6 participants | 30 days following completion of treatment for the first 6 participants | 
| Laryngectomy-free Survival in Locally Advanced Laryngeal Squamous Cell Carcinoma | This is the number of subjects that are laryngectomy-free at 18 months. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Laryngectomy-free Survival in Locally Advanced Laryngeal Squamous Cell Carcinoma | This is the number of subjects that are laryngectomy-free at 12 months. | 12 months |