Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Cancer; Head and Neck Squamous Cell Carcinoma; Oral Cancer; Tumor; Oropharynx Cancer; Cancer of Head and Neck; Oropharyngeal Cancer; Cancer, Advanced; Cancer, Metastatic; Tumor Metastasis; Tumor Recurrence; Tumor Neck; Oropharynx Cancer, Stage III; Oropharynx Cancer, Recurrent; Oropharynx Cancer, Metastatic
• Intervention / Treatment: Radiation: Radiation therapy; Drug: Cisplatin; Drug: Pembrolizumab

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).

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • University of Arizona Cancer Center
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Facility
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine, Siteman Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt-Ingram Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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)	Radiation: Radiation therapy; 70 Gy in 33-35 fractions; Other Names: Radiotherapy; Drug: Cisplatin; 100 mg/m2 Weeks 1, 4, and 7.; Other Names: Chemotherapy
Experimental: 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	Radiation: Radiation therapy; 70 Gy in 33-35 fractions; Other Names: Radiotherapy; Drug: Pembrolizumab; Pembrolizumab 200 mg IV infusion every 3 weeks x 20 cycles; Other Names: Immunotherapy

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PD-L1 expression correlations	compare the outcomes with RT/pembrolizumab in patients with tumors as a function of PD-L1 expression.	3 years

Collaborators and Investigators

• Sponsor: Loren Mell, MD
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Loren Mell, MD, University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2018
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: December 18, 2017
• First Submitted That Met QC Criteria: December 21, 2017
• First Posted (Actual): December 26, 2017

Study Record Updates

• Last Update Posted (Estimated): October 7, 2025
• Last Update Submitted That Met QC Criteria: October 1, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: chemotherapy; immunotherapy; cancer; Cisplatin; Radiotherapy; Pembrolizumab; T2; Head and Neck Squamous Cell Carcinoma; Head and Neck; T1; N2; pd-1; T3; T4; N1; p16+; M0; N3
• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Pathologic Processes; Neoplasms by Site; Disease Attributes; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplastic Processes; Carcinoma; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Carcinoma, Squamous Cell; Pathological Conditions, Signs and Symptoms; Squamous Cell Carcinoma of Head and Neck; Neoplasms; Recurrence; Neoplasm Metastasis; Head and Neck Neoplasms; Mouth Neoplasms; Oropharyngeal Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body; Therapeutics; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Biological Therapy; Immunomodulation; Cisplatin; Radiotherapy; pembrolizumab; Drug Therapy; Immunotherapy
• Other Study ID Numbers: 170862

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes