Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer

NCT03383094 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 170862
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 6

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).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• progression-free survival (PFS)

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

  3 years

Secondary Outcomes (4)

• overall survival

  3 years

• Acute toxicity

  3 months

• Late toxicity

  3 years

• Patterns of failure

  3 years

Other Outcomes (1)

• PD-L1 expression correlations

  3 years

Study Arms (2)

Control-radiotherapy/cisplatin

ACTIVE COMPARATOR

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; Drug: Cisplatin

Experimental-Radiotherapy/pembrolizumab

EXPERIMENTAL

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; Radiation: Radiation therapy

Interventions

Pembrolizumab DRUG

Pembrolizumab 200 mg IV infusion every 3 weeks x 20 cycles

Also known as: Immunotherapy

Experimental-Radiotherapy/pembrolizumab

Radiation therapy RADIATION

70 Gy in 33-35 fractions

Also known as: Radiotherapy

Control-radiotherapy/cisplatin; Experimental-Radiotherapy/pembrolizumab

Cisplatin DRUG

100 mg/m2 Weeks 1, 4, and 7.

Also known as: Chemotherapy

Control-radiotherapy/cisplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Loren Mell, MD: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (6)

University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

H. Lee Moffitt Cancer Center & Research Facility

Tampa, Florida, 33612, United States

Location

Washington University School of Medicine, Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Neoplasms; Head and Neck Neoplasms; Neoplasm Metastasis; Recurrence; Mouth Neoplasms; Oropharyngeal Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Immunotherapy; Radiotherapy; Cisplatin; Drug Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms by Site; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes; Mouth Diseases; Stomatognathic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Loren Mell, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Division of Clinical and Translational Research/ Department of Radiation Medicine

Study Record Dates

• First Submitted: December 18, 2017
• First Posted: December 26, 2017
• Study Start: March 15, 2018
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: October 7, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)