Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer

Cancer Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03383094
• Other study ID #: 170862
• Status: Recruiting
• Phase: Phase 2
• Start date: March 15, 2018
• Est. completion date: June 2025

Study information

• Verified date: May 2023
• Source: University of California, San Diego
• Contact: Loren Mell, MD
• Phone: (858) 246-0471
• Email: lmell[@]ucsd.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 114
• Est. completion date: June 2025
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cancer
• Cancer of Head and Neck
• Cancer, Advanced
• Cancer, Metastatic
• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Neoplasms
• Head and Neck Squamous Cell Carcinoma
• Mouth Neoplasms
• Neoplasm Metastasis
• Oral Cancer
• Oropharyngeal Cancer
• Oropharyngeal Neoplasms
• Oropharynx Cancer
• Oropharynx Cancer, Metastatic
• Oropharynx Cancer, Recurrent
• Oropharynx Cancer, Stage III
• Recurrence
• Squamous Cell Carcinoma of Head and Neck
• Tumor
• Tumor Metastasis
• Tumor Neck
• Tumor Recurrence

Intervention

Drug:
• Pembrolizumab
Pembrolizumab 200 mg IV infusion every 3 weeks x 20 cycles

Radiation:
• Radiation therapy
70 Gy in 33-35 fractions

Drug:
• Cisplatin
100 mg/m2 Weeks 1, 4, and 7.

Locations

Country	Name	City	State
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Washington University School of Medicine, Siteman Cancer Center	Saint Louis	Missouri
United States	H. Lee Moffitt Cancer Center & Research Facility	Tampa	Florida
United States	University of Arizona Cancer Center	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Loren Mell, MD	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	PD-L1 expression correlations	compare the outcomes with RT/pembrolizumab in patients with tumors as a function of PD-L1 expression.	3 years
Primary	progression-free survival (PFS)	time from randomization to progression/relapse or death from any cause.	3 years
Secondary	overall survival	time from randomization to death from any cause	3 years
Secondary	Acute toxicity	Toxicities due to therapy occurring within 3 months of therapy completion based on CTCAE criteria using questionnaires	3 months
Secondary	Late toxicity	Toxicity due to therapy occurring greater than 3 months after completion of therapy based on CTCAE criteria using questionnaires	3 years
Secondary	Patterns of failure	Local and regional and distant recurrence of cancer and causes of death from competing events	3 years