Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer

Study Overview
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Brief Summary
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The purpose of this study is to compare any good or bad effects of using pembrolizumab (an experimental drug) and radiation therapy (RT), compared to using cisplatin chemotherapy and radiation therapy (RT) in the treatment of patients with head and neck squamous cell carcinoma (HNSCC).

Detailed Description
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This study is a prospective, multi-institutional, open-label, randomized phase II trial that will evaluate the efficacy of concurrent and adjuvant pembrolizumab with radiation therapy (RT) versus RT plus cisplatin in intermediate/high-riskp16-positive locoregionally advanced head and neck squamous cell carcinoma (HNSCC). The primary endpoint is progression-free survival (PFS).

Official Title
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Phase II Randomized Trial of Radiotherapy With Concurrent and Adjuvant Pembrolizumab (Keytruda®) Versus Concurrent Chemotherapy in Patients With Advanced/Intermediate-Risk p16+ Head and Neck Squamous Cell Carcinoma (KEYCHAIN)

Conditions
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Head and Neck Squamous Cell Carcinoma, Cancer, Cancer of Head and Neck, Cancer, Advanced, Cancer, Metastatic, Tumor, Tumor Recurrence, Tumor Neck, Tumor Metastasis, Oral Cancer, Oropharyngeal Cancer, Oropharynx Cancer, Oropharynx Cancer, Stage III, Oropharynx Cancer, Recurrent, Oropharynx Cancer, Metastatic

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: p16-positive squamous cell carcinoma of the pharynx, larynx or oral cavity High-Intermediate Risk Disease, defined as: T1-T3 N2 M0 or T3 N1 M0 or any stage III (T4 or N3) p16+ squamous cell carcinoma of the oropharynx (AJCC 8th edition staging system) T1-2 N1-3 M0 or T3-4 N0-3 M0 (stage III-IVB) p16+ squamous cell carcinoma of the hypopharynx or larynx T1-2 N2-3 M0 or T3-4 N0-3 M0 (stage III-IVB) p16+ squamous cell carcinoma of the nasopharynx Inoperable T4 N0-3 M0 (stage IVA-IVB) p16+ squamous cell carcinoma of the oral cavity Measurable disease based on RECIST 1.1 Adequate hematologic function within 28 days prior to registration Adequate renal and hepatic function Female subject of childbearing potential should have a negative pregnancy test Female subjects of childbearing potential must agree to use an adequate method of contraception for the course of the study Male subjects must agree to use an adequate method of contraception for the course of the study Exclusion Criteria: Prior malignancy within the past 3 years (except non-melanomatous skin cancer and early stage treated prostate cancer); Prior head and neck radiation, chemotherapy, or immunotherapy; Prior oncologic (radical) surgery to the primary site; Documented evidence of distant metastases; Severe, active co-morbidity defined as follows: Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; Transmural myocardial infarction within the last 6 months; Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration; Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. Any medical or psychiatric illness, which, in the opinion of the principal investigator, would compromise the patient's ability to tolerate this treatment; Psychiatric/social situations that would limit compliance with study requirements Hypersensitivity to pembrolizumab or any of its excipients. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Known history of, or any evidence of active, non-infectious pneumonitis. Active infection requiring systemic therapy. 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-PD-1, anti-PD-L1, or anti-PD-L2 agent. Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 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 of planned start of study therapy.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control-radiotherapy/cisplatin<br>Intensity-modulated radiation therapy to 70 Gy in 33-35 fractions over 6.5 weeks plus concurrent cisplatin 100 mg/m2 every 3 weeks for 3 cycles (7 weeks) | Radiation: Radiation therapy<br>* 70 Gy in 33-35 fractions<br>* Other names: Radiotherapy;Drug: Cisplatin<br>* 100 mg/m2 Weeks 1, 4, and 7.<br>* Other names: Chemotherapy;|
| Experimental: Experimental-Radiotherapy/pembrolizumab<br>Intensity-modulated radiation therapy to 70 Gy in 33-35 fractions over 6.5 weeks plus concurrent and adjuvant pembrolizumab 200 mg IV infusion every 3 weeks x 20 cycles | Drug: Pembrolizumab<br>* Pembrolizumab 200 mg IV infusion every 3 weeks x 20 cycles<br>* Other names: Immunotherapy;Radiation: Radiation therapy<br>* 70 Gy in 33-35 fractions<br>* Other names: Radiotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival (PFS) | time from randomization to progression/relapse or death from any cause. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | time from randomization to death from any cause | 3 years | 
| Acute toxicity | Toxicities due to therapy occurring within 3 months of therapy completion based on CTCAE criteria using questionnaires | 3 months | 
| Late toxicity | Toxicity due to therapy occurring greater than 3 months after completion of therapy based on CTCAE criteria using questionnaires | 3 years | 
| Patterns of failure | Local and regional and distant recurrence of cancer and causes of death from competing events | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T2, p16+, immunotherapy, pd-1, chemotherapy, T3, N2, M0, T4, N3, N1, cancer, Head and Neck, Pembrolizumab, Cisplatin, Radiotherapy, Head and Neck Squamous Cell Carcinoma, T1