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)
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)
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).
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).
Inclusion Criteria:
p16-positive squamous cell carcinoma of the pharynx, larynx or oral cavity
High-Intermediate Risk Disease, defined as:
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:
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.
St Louis, Missouri 63110, United States