This study is being done to evaluate the efficacy of Pembrolizumab, concomitant with and following standard of care definitive radiation, for locally advanced squamous cell carcinoma of the head and neck patients who are not good candidates for Cisplatin.
This open label, phase II trial will enroll 29 subjects in order to evaluate the efficacy of Pembrolizumab, concomitant with and following standard of care definitive radiation for locally advanced squamous cell carcinoma head and neck patients who are not good candidates for Cisplatin. Objectives include estimating progression free survival and overall survival, response rates, safety and toxicity, and quality of life in these patients. Correlative studies, based on serial blood collections and tumor samples, may be done under a separate protocol based on availability of archival diagnostic tissue.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
29
Pembrolizumab, 200 mg IV during cycle visits every 3-weeks for up to 6 cycles, or until toxicities are no longer tolerable
Eligible participants will receive Intensity Modulated Radiation Therapy daily x 7 weeks
John Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
20 Week Progression Free Survival Rate
the proportion of patients who are alive and free of progression from disease at 20 weeks from the start of treatment
Time frame: 20 weeks after D1 of treatment
One Year Progression Free Survival Rate
the proportion of patients who are alive and free of progression from disease atoneyears from the start of treatment
Time frame: 1 years after D1 of treatment
Two Year Progression Free Survival Rate
the proportion of patients who are alive and free of progression from disease at two years from the start of treatment
Time frame: 2 years after D1 of treatment
Median Progression Free Survival
Progression-free survival is defined as the time from D1 of treatment to progression or death from any cause. The median was not reached, thus Kaplan Meier's estimated rate at 5 years is reported.
Time frame: up to 5 years after D1 of treatment
One Year Overall Survival Rate
the proportion of patients who are alive at one year after Day 1 of treatment
Time frame: 1 year after Day 1 of treatment
Two Year Overall Survival Rate
the proportion of patients who are alive at two years after Day 1 of treatment
Time frame: 2 years after Day 1 of treatment
Proportion of Participants Who Received <95% of Intended Dose of Radiation
Evaluate the safety of the proposed regimen by Estimating the proportion of patients who receive \<95% of the intended dose of radiation (i.e., \<67 Gray)
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Time frame: 7 weeks
Number of Participants With Clinically Relevant Adverse Events
Safety was assessed by documenting clinically relevant adverse events, defined as events reported by both the clinician and participant related to concurrent radiation plus pembrolizumab. Clinicians classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0). The grading (severity) scale for each AE term: Grade (G) 1 Mild; asymptomatic/mild symptoms; clinical/diagnostic observations only; G 2 Moderate; G 3 Severe or medically significant but not immediately life-threatening; hospitalization/prolongation of hospitalization indicated; disabling; G 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. Patient assessed toxicity were classified based on the Patient-Reported Outcome version of the CTCAE (PRO-CTCAE) which measures the severity, interference, and frequency of events on a 5 point likert scale (0-4) with a higher score indicating worse or more bothersome event
Time frame: Monitored continuously from D1 of treatment through 40 weeks.
Overall Response Rate
Overall response rate will be determined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) which defines Complete Response (CR) as Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Overall Response Rate (ORR) = CR + PR/total number of subjects.
Time frame: 2 years after start of treatment
Complete Response Rate
complete response rate will be determined using RECIST 1.1 and is defined as the percentage of participants who achieve a Complete response (CR)-Disappearance of all target lesions. Any pathological lymph node (LN) (whether target or non-target) must have decreased in short axis to \<10mm.
Time frame: 2 years after start of treatment
Five Years Locoregional Recurrence Rate
Time to locoregional recurrence is defined from Day 1 of treatment until the first locoregional progression
Time frame: 5 years from start of treatment
Five Years Distant Metastasis Rate
Time to distant metastasis is defined as the time from day 1 of treatment to progression of disease at a distant site; deaths or other progressions will be censored
Time frame: 5 years from start of treatment
Quality of Life Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-HN)
The FACT-HN is the FACT-General (FACT-G) and a head and neck cancer specific (HNC) subscale given at baseline, at end of treatment, and at first follow-up visit. The FACT-G is a measure of general QOL with Items rated by patients on a Likert scale from 0 to 4, assessing function in 4 domains: physical well-being (PWB) (7 items, score range 0-28), social-family well-being (SFWB) (7 items, score range 0-28), emotional well-being (EWB) (6 items, score range 0-24) and functional well-being (FWB) (7 items, score range 0-28). The HNC subscale has 12 items and a score range from 0 to 48. Higher scores represent better QOL.
Time frame: At baseline, 10 and 20 weeks after initiation of treatment