Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer

Sponsor
Loren Mell, MD (Other)
Overall Status
Recruiting
CT.gov ID
NCT03383094
Collaborator
Merck Sharp & Dohme Corp. (Industry)
114
Enrollment
7
Locations
2
Arms
74.6
Anticipated Duration (Months)
16.3
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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).

Study Design

Study Type:
Interventional
Anticipated Enrollment :
114 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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)
Actual Study Start Date :
Mar 15, 2018
Anticipated Primary Completion Date :
Apr 1, 2023
Anticipated Study Completion Date :
Jun 1, 2024

Arms and Interventions

ArmIntervention/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

    Drug: Pembrolizumab
    Pembrolizumab 200 mg IV infusion every 3 weeks x 20 cycles
    Other Names:
  • Immunotherapy
  • Radiation: Radiation therapy
    70 Gy in 33-35 fractions
    Other Names:
  • Radiotherapy
  • Outcome Measures

    Primary Outcome Measures

    1. progression-free survival (PFS) [3 years]

      time from randomization to progression/relapse or death from any cause.

    Secondary Outcome Measures

    1. overall survival [3 years]

      time from randomization to death from any cause

    2. Acute toxicity [3 months]

      Toxicities due to therapy occurring within 3 months of therapy completion based on CTCAE criteria using questionnaires

    3. Late toxicity [3 years]

      Toxicity due to therapy occurring greater than 3 months after completion of therapy based on CTCAE criteria using questionnaires

    4. Patterns of failure [3 years]

      Local and regional and distant recurrence of cancer and causes of death from competing events

    Other Outcome Measures

    1. PD-L1 expression correlations [3 years]

      compare the outcomes with RT/pembrolizumab in patients with tumors as a function of PD-L1 expression.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of Arizona Cancer CenterTucsonArizonaUnited States85719
    2UC San Diego Moores Cancer CenterLa JollaCaliforniaUnited States92093
    3Yale Cancer CenterNew HavenConnecticutUnited States06520
    4H. Lee Moffitt Cancer Center & Research FacilityTampaFloridaUnited States33612
    5Washington University School of Medicine, Siteman Cancer CenterSaint LouisMissouriUnited States63110
    6University of Cincinnati Medical CenterCincinnatiOhioUnited States45219
    7Vanderbilt-Ingram Cancer CenterNashvilleTennesseeUnited States37203

    Sponsors and Collaborators

    • Loren Mell, MD
    • Merck Sharp & Dohme Corp.

    Investigators

    • Principal Investigator: Loren Mell, MD, University of California, San Diego

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Loren Mell, MD, Director, Division of Clinical and Translational Research/ Department of Radiation Medicine, University of California, San Diego
    ClinicalTrials.gov Identifier:
    NCT03383094
    Other Study ID Numbers:
    • 170862
    First Posted:
    Dec 26, 2017
    Last Update Posted:
    Oct 8, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Keywords provided by Loren Mell, MD, Director, Division of Clinical and Translational Research/ Department of Radiation Medicine, University of California, San Diego
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 8, 2021