Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer

May 1, 2023 updated by: Loren Mell, MD

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

Recruiting

Conditions

Intervention / Treatment

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 (Anticipated)

114

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Loren Mell, MD
  • Phone Number: (858) 246-0471
  • Email: lmell@ucsd.edu

Study Contact Backup

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • Recruiting
        • University of Arizona Cancer Center
        • Principal Investigator:
          • Ricklie Julian, MD
        • Contact:
          • Alysha Zeoli
        • Contact:
          • Phone Number: 520-694-9056
    • California
      • La Jolla, California, United States, 92093
        • Recruiting
        • UC San Diego Moores Cancer Center
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • Yale Cancer Center
        • Contact:
          • Jennifer Pope, CCRP
          • Phone Number: 203-737-5801
        • Principal Investigator:
          • Melissa Young, MD, PhD
    • Florida
      • Tampa, Florida, United States, 33612
        • Recruiting
        • H. Lee Moffitt Cancer Center & Research Facility
        • Contact:
          • Elisa Lemerond
          • Phone Number: 819-745-2800
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine, Siteman Cancer Center
        • Contact:
          • Melissa Butler
          • Phone Number: 314-747-8706
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Recruiting
        • University of Cincinnati Medical Center
        • Contact:
          • Aubrey Hamilton
          • Phone Number: 513-584-1492
        • Contact:
          • Sarah Wilson
          • Phone Number: 513-584-8216
        • Principal Investigator:
          • Trisha Wise-Draper, MD, PhD
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Vanderbilt-Ingram Cancer Center
        • Contact:
          • Kathy Taylor
          • Phone Number: 615-875-0060
        • Principal Investigator:
          • Mike Gibson, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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 Frame: 3 years
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 Frame: 3 years
time from randomization to death from any cause
3 years
Acute toxicity
Time Frame: 3 months
Toxicities due to therapy occurring within 3 months of therapy completion based on CTCAE criteria using questionnaires
3 months
Late toxicity
Time Frame: 3 years
Toxicity due to therapy occurring greater than 3 months after completion of therapy based on CTCAE criteria using questionnaires
3 years
Patterns of failure
Time Frame: 3 years
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
Time Frame: 3 years
compare the outcomes with RT/pembrolizumab in patients with tumors as a function of PD-L1 expression.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Loren Mell, MD

Collaborators

Merck Sharp & Dohme LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 15, 2018

Primary Completion (Anticipated)

August 1, 2024

Study Completion (Anticipated)

June 1, 2025

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 (Actual)

May 3, 2023

Last Update Submitted That Met QC Criteria

May 1, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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