Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer

NCT ID: NCT03383094

Last Updated: 2025-10-07

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 126 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-15
• Study Completion Date: 2027-12-31

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).

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: ACTIVE_COMPARATOR

Radiation therapy

Intervention Type: RADIATION

70 Gy in 33-35 fractions

Cisplatin

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab 200 mg IV infusion every 3 weeks x 20 cycles

Radiation therapy

Intervention Type: RADIATION

70 Gy in 33-35 fractions

Interventions

Pembrolizumab

Pembrolizumab 200 mg IV infusion every 3 weeks x 20 cycles

Intervention Type: DRUG

Radiation therapy

70 Gy in 33-35 fractions

Intervention Type: RADIATION

Cisplatin

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

Intervention Type: DRUG

Other Intervention Names

Immunotherapy; Radiotherapy; Chemotherapy

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Loren Mell, MD

OTHER

Sponsor Role: lead

Responsible Party

Loren Mell, MD

Director, Division of Clinical and Translational Research/ Department of Radiation Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Loren Mell, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

University of Arizona Cancer Center

Tucson, Arizona, United States

UC San Diego Moores Cancer Center

La Jolla, California, United States

H. Lee Moffitt Cancer Center & Research Facility

Tampa, Florida, United States

Washington University School of Medicine, Siteman Cancer Center

St Louis, Missouri, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

170862

Identifier Type: -

Identifier Source: org_study_id