Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer

• ClinicalTrials.gov Identifier: NCT03383094
• Recruitment Status: Recruiting
• First Posted: December 26, 2017
• Last Update Posted: October 8, 2021
• Sponsor: Loren Mell, MD
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Loren Mell, MD, University of California, San Diego

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).

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).

Study Design

• 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 2023
• Estimated Study Completion Date: June 2024

Arms and Interventions

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

Outcome Measures

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.

Eligibility Criteria

• 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.

Contacts and Locations

Contacts

Contact: Loren Mell, MD; (858) 246-0471; lmell@ucsd.edu

Contact: Gerald Henderson; gehenderson@ucsd.edu

Locations

United States, Arizona

University of Arizona Cancer Center; Recruiting

Tucson, Arizona, United States, 85719

Contact: Alysha Zeoli

Contact 520-694-9056

Principal Investigator: Ricklie Julian, MD

United States, California

UC San Diego Moores Cancer Center; Recruiting

La Jolla, California, United States, 92093

Contact: Khushbu Singh, MBBS, CCRP 858-246-2604

Principal Investigator: Loren Mell, MD

United States, Connecticut

Yale Cancer Center; Recruiting

New Haven, Connecticut, United States, 06520

Contact: Jennifer Pope, CCRP 203-737-5801

Principal Investigator: Melissa Young, MD, PhD

United States, Florida

H. Lee Moffitt Cancer Center & Research Facility; Recruiting

Tampa, Florida, United States, 33612

Contact: Elisa Lemerond 819-745-2800

Principal Investigator: Jimmy Caudell, MD

United States, Missouri

Washington University School of Medicine, Siteman Cancer Center; Recruiting

Saint Louis, Missouri, United States, 63110

Contact: Melissa Butler 314-747-8706

Principal Investigator: Douglas Adkins, MD

United States, Ohio

University of Cincinnati Medical Center; Recruiting

Cincinnati, Ohio, United States, 45219

Contact: Aubrey Hamilton 513-584-1492

Contact: Sarah Wilson 513-584-8216

Principal Investigator: Trisha Wise-Draper, MD, PhD

United States, Tennessee

Vanderbilt-Ingram Cancer Center; Recruiting

Nashville, Tennessee, United States, 37203

Contact: Kathy Taylor 615-875-0060

Principal Investigator: Mike Gibson, MD

Sponsors and Collaborators

Loren Mell, MD

Merck Sharp & Dohme LLC

Investigators

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

More Information

• 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: December 26, 2017
• Last Update Posted: October 8, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• 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, 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:

Carcinoma; Carcinoma, Squamous Cell; Neoplasm Metastasis; 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; Neoplastic Processes; 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