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)
Overview
- Phase
- Phase 2
- Intervention
- Radiation therapy
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Sponsor
- Loren Mell, MD
- Enrollment
- 126
- Locations
- 6
- Primary Endpoint
- progression-free survival (PFS)
- Status
- Active, Not Recruiting
- Last Updated
- 6 months ago
Overview
Brief Summary
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
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).
Investigators
Loren Mell, MD
Director, Division of Clinical and Translational Research/ Department of Radiation Medicine
University of California, San Diego
Eligibility Criteria
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
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
Arms & Interventions
Control-radiotherapy/cisplatin
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)
Intervention: Radiation therapy
Control-radiotherapy/cisplatin
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)
Intervention: Cisplatin
Experimental-Radiotherapy/pembrolizumab
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
Intervention: Pembrolizumab
Experimental-Radiotherapy/pembrolizumab
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
Intervention: Radiation therapy
Outcomes
Primary Outcomes
progression-free survival (PFS)
Time Frame: 3 years
time from randomization to progression/relapse or death from any cause.
Secondary Outcomes
- overall survival(3 years)
- Late toxicity(3 years)
- Acute toxicity(3 months)
- Patterns of failure(3 years)