search
Back to results

Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer

Primary Purpose

Head and Neck Squamous Cell Carcinoma, Cancer, Cancer of Head and Neck

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pembrolizumab
Radiation therapy
Cisplatin
Sponsored by
Loren Mell, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Squamous Cell Carcinoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Arizona Cancer CenterRecruiting
  • UC San Diego Moores Cancer CenterRecruiting
  • Yale Cancer CenterRecruiting
  • H. Lee Moffitt Cancer Center & Research FacilityRecruiting
  • Washington University School of Medicine, Siteman Cancer CenterRecruiting
  • University of Cincinnati Medical CenterRecruiting
  • Vanderbilt-Ingram Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Control-radiotherapy/cisplatin

Experimental-Radiotherapy/pembrolizumab

Arm Description

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)

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

Outcomes

Primary Outcome Measures

progression-free survival (PFS)
time from randomization to progression/relapse or death from any cause.

Secondary Outcome Measures

overall survival
time from randomization to death from any cause
Acute toxicity
Toxicities due to therapy occurring within 3 months of therapy completion based on CTCAE criteria using questionnaires
Late toxicity
Toxicity due to therapy occurring greater than 3 months after completion of therapy based on CTCAE criteria using questionnaires
Patterns of failure
Local and regional and distant recurrence of cancer and causes of death from competing events

Full Information

First Posted
December 18, 2017
Last Updated
May 1, 2023
Sponsor
Loren Mell, MD
Collaborators
Merck Sharp & Dohme LLC
search

1. Study Identification

Unique Protocol Identification Number
NCT03383094
Brief Title
Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer
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)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 15, 2018 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Loren Mell, MD
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

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
Data Monitoring Committee
Yes

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
114 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control-radiotherapy/cisplatin
Arm Type
Active Comparator
Arm Description
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)
Arm Title
Experimental-Radiotherapy/pembrolizumab
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Immunotherapy
Intervention Description
Pembrolizumab 200 mg IV infusion every 3 weeks x 20 cycles
Intervention Type
Radiation
Intervention Name(s)
Radiation therapy
Other Intervention Name(s)
Radiotherapy
Intervention Description
70 Gy in 33-35 fractions
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Chemotherapy
Intervention Description
100 mg/m2 Weeks 1, 4, and 7.
Primary Outcome Measure Information:
Title
progression-free survival (PFS)
Description
time from randomization to progression/relapse or death from any cause.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
overall survival
Description
time from randomization to death from any cause
Time Frame
3 years
Title
Acute toxicity
Description
Toxicities due to therapy occurring within 3 months of therapy completion based on CTCAE criteria using questionnaires
Time Frame
3 months
Title
Late toxicity
Description
Toxicity due to therapy occurring greater than 3 months after completion of therapy based on CTCAE criteria using questionnaires
Time Frame
3 years
Title
Patterns of failure
Description
Local and regional and distant recurrence of cancer and causes of death from competing events
Time Frame
3 years
Other Pre-specified Outcome Measures:
Title
PD-L1 expression correlations
Description
compare the outcomes with RT/pembrolizumab in patients with tumors as a function of PD-L1 expression.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Loren Mell, MD
Phone
(858) 246-0471
Email
lmell@ucsd.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Gerald Henderson
Email
gehenderson@ucsd.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Loren Mell, MD
Organizational Affiliation
University of California, San Diego
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85719
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alysha Zeoli
Phone
520-694-9056
First Name & Middle Initial & Last Name & Degree
Ricklie Julian, MD
Facility Name
UC San Diego Moores Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Khushbu Singh, MBBS, CCRP
Phone
858-246-2604
First Name & Middle Initial & Last Name & Degree
Loren Mell, MD
Facility Name
Yale Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Pope, CCRP
Phone
203-737-5801
First Name & Middle Initial & Last Name & Degree
Melissa Young, MD, PhD
Facility Name
H. Lee Moffitt Cancer Center & Research Facility
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elisa Lemerond
Phone
819-745-2800
First Name & Middle Initial & Last Name & Degree
Jimmy Caudell, MD
Facility Name
Washington University School of Medicine, Siteman Cancer Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Melissa Butler
Phone
314-747-8706
First Name & Middle Initial & Last Name & Degree
Douglas Adkins, MD
Facility Name
University of Cincinnati Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aubrey Hamilton
Phone
513-584-1492
First Name & Middle Initial & Last Name & Degree
Sarah Wilson
Phone
513-584-8216
First Name & Middle Initial & Last Name & Degree
Trisha Wise-Draper, MD, PhD
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kathy Taylor
Phone
615-875-0060
First Name & Middle Initial & Last Name & Degree
Mike Gibson, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer

We'll reach out to this number within 24 hrs