Pembrolizumab + Radiation for Locally Adv SCC of the Head and Neck (SCCHN) Not Eligible Cisplatin

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Pembrolizumab and Radiation for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN) Not Eligible for Cisplatin Therapy

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: Pembrolizumab
* Radiation: Intensity Modulated Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be willing and able to provide written informed consent/assent for the trial Be greater than or equal to 18 years of age Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 1 Histologically or cytologically confirmed stage III-IV (non-metastatic) squamous cell carcinoma of the head and neck as defined by American Joint Committee on Cancer. Nasopharyngeal cancer patients will be excluded. Ineligible for high dose cisplatin therapy; the reason for ineligibility must be defined. Demonstrate adequate organ function. All screening labs should be performed within 14 days of treatment initiation. No prior curative attempts for this cancer (i.e., surgery, radiation and/or other). Female patients of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. Serum pregnancy test may be required. Female patients of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Male patients should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. As determined by the enrolling physician or protocol designee, ability of the patient to understand and comply with study procedures for the entire length of the study. Consent for the use of any residual material from biopsy (archival tissue) and serial blood draws will be required for enrollment. Exclusion Criteria: If currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier Had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered from adverse events due to a previously administered agent. Has a known additional malignancy that is metastatic, progressing or requires active treatment. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease even if resolved; patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Has clinical or radiologic evidence of interstitial lung disease or active, non-infectious pneumonitis Has an active infection requiring systemic therapy. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. Has inadequate home environment or social support to safely complete the trial procedures. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. Has received prior therapy with an anti-programmed cell death (PD-1), anti-PD-L1, anti-PD-L1, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody. Has a known history of Human Immunodeficiency Virus (HIV) HIV 1/2 antibodies) Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C )e.g., HCV RNA [qualitative] is detected). Has received a live vaccine within 30 days prior to the first dose of trial treatment. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open label<br>Pembrolizumab | Drug: Pembrolizumab<br>* Pembrolizumab, 200 mg IV during cycle visits every 3-weeks for up to 6 cycles, or until toxicities are no longer tolerable<br>* Other names: Keytruda;|
| Other: Radiation<br>Intensity Modulated Radiation Therapy (IMRT) | Radiation: Intensity Modulated Radiation Therapy<br>* Eligible participants will receive Intensity Modulated Radiation Therapy daily x 7 weeks<br>* Other names: IMRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 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 | 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. | up to 5 years after D1 of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| One Year Overall Survival Rate | the proportion of patients who are alive at one year after Day 1 of treatment | 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 | 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) | 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 | 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. | 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. | 2 years after start of treatment | 
| Time to Locoregional Recurrence | Time to locoregional recurrence is defined from Day 1 of treatment until the first locoregional progression | 5 years from start of treatment | 
| Time to Distant Metastasis | 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 | 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. | At baseline, 10 and 20 weeks after initiation of treatment |