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Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer

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ClinicalTrials.gov Identifier: NCT03383094
Recruitment Status : Recruiting
First Posted : December 26, 2017
Last Update Posted : March 7, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Loren Mell, MD, University of California, San Diego

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).

Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma Cancer Cancer of Head and Neck Cancer, Advanced Cancer, Metastatic Tumor Tumor Recurrence Tumor Neck Tumor Metastasis Oral Cancer Oropharyngeal Cancer Oropharynx Cancer Oropharynx Cancer, Stage III Oropharynx Cancer, Recurrent Oropharynx Cancer, Metastatic Drug: Pembrolizumab Radiation: Radiation therapy Drug: Cisplatin Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : March 15, 2018
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : June 2024


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 Name: Radiotherapy

Drug: Cisplatin
100 mg/m2 Weeks 1, 4, and 7.
Other Name: 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 Name: Immunotherapy

Radiation: Radiation therapy
70 Gy in 33-35 fractions
Other Name: Radiotherapy




Primary Outcome Measures :
  1. progression-free survival (PFS) [ Time Frame: 3 years ]
    time from randomization to progression/relapse or death from any cause.


Secondary Outcome Measures :
  1. overall survival [ Time Frame: 3 years ]
    time from randomization to death from any cause

  2. Acute toxicity [ Time Frame: 3 months ]
    Toxicities due to therapy occurring within 3 months of therapy completion based on CTCAE criteria using questionnaires

  3. 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

  4. Patterns of failure [ Time Frame: 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 [ Time Frame: 3 years ]
    compare the outcomes with RT/pembrolizumab in patients with tumors as a function of PD-L1 expression.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03383094


Contacts
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Contact: Loren Mell, MD (858) 246-0471 lmell@ucsd.edu
Contact: Gerald Henderson gehenderson@ucsd.edu

Locations
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United States, California
UC San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Sponsors and Collaborators
Loren Mell, MD
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Loren Mell, MD University of California, San Diego

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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     History of Changes
Other Study ID Numbers: 170862
First Posted: December 26, 2017    Key Record Dates
Last Update Posted: March 7, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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, University of California, San Diego:
cancer
Head and Neck
Pembrolizumab
Cisplatin
Radiotherapy
Head and Neck Squamous Cell Carcinoma
p16+
immunotherapy
pd-1
chemotherapy
T1
T2
T3
N2
M0
T4
N3
N1
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Oropharyngeal Neoplasms
Mouth Neoplasms
Head and Neck Neoplasms
Recurrence
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Pathologic Processes
Disease Attributes
Neoplasms by Site
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Mouth Diseases
Cisplatin
Pembrolizumab
Antineoplastic Agents
Antineoplastic Agents, Immunological