First Line Weekly Chemo/Immunotherapy for Metastatic Head/Neck Squamous Cell Carcinoma Patients

Study Overview
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Brief Summary
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The purpose of this research is to see what effects the treatment regimen chemotherapy (carboplatin and paclitaxel) plus immunotherapy (pembrolizumab), has on patients who have been diagnosed with head/neck squamous cell carcinoma and are unable to take the drug 5-fluorouracil

Detailed Description
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Primary Objective: To determine if six (6) cycles of pembrolizumab with weekly carboplatin and paclitaxel for the 1st line treatment of metastatic head/neck squamous cell carcinoma patients increases the radiographic response rate as compared to the historical rate for pembrolizumab alone. Secondary Objective(s): To determine if six (6) cycles of pembrolizumab with weekly carboplatin and paclitaxel for the 1st line treatment of metastatic head/neck squamous cell carcinoma patients increases median overall survival (OS) as compared to the historical rate reported for pembrolizumab alone. To determine if six (6) cycles of pembrolizumab with weekly carboplatin and paclitaxel followed by pembrolizumab alone for the 1st line treatment of metastatic head/neck squamous cell carcinoma patients increases the median progression-free survival (PFS) as compared to the historical rate reported for pembrolizumab alone. To determine the toxicity profile of six (6) cycles of pembrolizumab with weekly carboplatin/paclitaxel/pembrolizumab alone for the 1st line treatment of metastatic head/neck squamous cell carcinoma patients, measured as the proportion of patients with discontinuation of any study drug due to any adverse event of any cause, as compared to the historical proportion reported for platinum/5FU/ pembrolizumab (33%).

Official Title
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Phase II Study of First Line Weekly Chemo/Immunotherapy for Metastatic Head/Neck Squamous Cell Carcinoma Patients

Conditions
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Head Neck Cancer, Metastatic Squamous Cell Carcinoma, Oral Cavity Squamous Cell Carcinoma, Oropharynx Squamous Cell Carcinoma, Hypopharynx Squamous Cell Carcinoma, Larynx Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Pembrolizumab
* Drug: Carboplatin
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recurrent or metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, larynx or neck node with occult primary but suspected to be non-cutaneous head/neck that is incurable by local therapies (i.e. radiation or surgery) and either locoregionally advanced or with at least one distant metastasis. Histologic or cytologic confirmation of malignancy by pathology report. Not a candidate for infusional 5FU (mucositis, 5-day infusional pump not feasible, patient refusal, other). 18 years old or greater. ECOG performance status of 0-2. Life expectancy of greater than 3 months. Patients must have normal organ and marrow function as defined: Absolute neutrophil count greater than or equal to 1,000/mcL, platelets greater than or equal to 75,000/mcL, total bilirubin less than or equal to 2 mg/dL Ability to understand and the willingness to sign an IRB-approved informed consent document (either directly or via a legally authorized representative). Exclusion Criteria: No prior systemic cancer-directed therapy administered in the recurrent or metastatic setting. Prior treatments are allowed if they were administered with curative intent prior to incurable progression of disease. Prior treatments for other cancers are also allowed. Untreated, symptomatic central nervous system (CNS) metastases. Active autoimmune disease requiring systemic immunosuppression. History of autoimmune pneumonitis requiring high-dose systemic steroids (equivalent prednisone >20 mg/day for >1 week). History of greater than or equal to Grade 3 hypersensitivity reaction to carboplatin or paclitaxel. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Pregnant women are excluded from this study because paclitaxel and carboplatin are Class D agents with significant potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these drugs, breastfeeding should be discontinued during the study.

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: Combination of Chemotherapy and Immunotherapy<br>The intervention will be administered on an outpatient basis. The treatment regimen will consist of combination chemotherapy and immunotherapy administered as: Pembrolizumab PLUS Carboplatin PLUS Paclitaxel. | Drug: Pembrolizumab<br>* Pembrolizumab 200 mg intravenously (IV) on day 1 of each 3-week cycle<br>Drug: Carboplatin<br>* Carboplatin dosed for area under the curve (AUC) 1.5 IV on days 1, 8, 15 of each 3-week cycle<br>Drug: Paclitaxel<br>* Paclitaxel 45 mg/m2 on days 1, 8, 15 of 3-week cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Using RECIST 1.1 will be defined as the percentage of analyzed participants with a complete response - defined as disappearance of all target lesions; or partial response - defined as decrease by ≥ 30% in sum of longest diameter of target lesions when compared to the historical objective response rate (19%) reported for pembrolizumab alone; stable disease (SD): Not meeting criteria for CR, PR, or PD; progressive disease (PD): Increase by ≥ 20% in sum of longest diameter of target lesions or the appearance of one or more new lesions. | At 18 weeks on study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Median survival rate will be defined as the time from study registration to death due to any cause and as compared to the historical median reported for pembrolizumab alone. The Kaplan-Meier method will be used to generate survival curves with the intention-to-treat population. Data for patients who are alive or lost to follow-up will be censored for overall survival at the date they were last known to be alive | Up to 2 years | 
| Progression-Free Survival | Median progression-free survival (PFS) defined as the time from study registration to the first documented progressive disease (PD) per RECIST v1.1 criteria (defined as increase by ≥ 20% in sum of longest diameter of target lesions or the appearance of one or more new lesions) based on non-blinded central imaging or else death due to any cause, whichever occurred first; and as compared to the historical value reported for pembrolizumab alone. The Kaplan-Meier method will be used to generate survival curves with the intention-to-treat population. | Up to 2 years | 
| Number of Participants with Discontinuation of Study Drug due to Adverse Effects of Any Cause | Participants with discontinuation of any study drug due to adverse events of any cause before 18 weeks as compared to the historical value reported for platinum/5FU/pembrolizumab. | Up to 18 weeks |