Combining Radiation Therapy With Immunotherapy for the Treatment of Metastatic Squamous Cell Carcinoma of the Head and Neck

Running, not enrolling · Phase 3

Conditions studied: Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma, Metastatic Laryngeal Squamous Cell Carcinoma, Metastatic Oral Cavity Squamous Cell Carcinoma, Metastatic Oropharyngeal Squamous Cell Carcinoma, Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8, Stage IV Hypopharyngeal Carcinoma AJCC v8, Stage IV Laryngeal Cancer AJCC v8, Stage IV Lip and Oral Cavity Cancer AJCC v8, Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8

In brief

This phase III trial compares pembrolizumab with radiation therapy to pembrolizumab without radiation therapy (standard therapy) given after pembrolizumab plus chemotherapy for the treatment of patients with squamous cell carcinoma of the head and neck that has spread from where it first started (primary site) to other places in the body (metastatic). Pembrolizumab is a type of immunotherapy that stimulates the body's immune system to fight cancer cells. Pembrolizumab targets and blocks a protein called PD-1 on the surface of certain immune cells called T-cells. Blocking PD-1 triggers the T-cells to find and kill cancer cells. Radiation therapy uses high-powered rays to kill cancer cells. Giving radiation with pembrolizumab may be more effective at treating patients with metastatic head and neck cancer than the standard therapy of giving pembrolizumab alone.

Key facts

Study ID

NCT05721755

Run by

ECOG-ACRIN Cancer Research Group

People needed

290

Starts

2023-06-08

Expected to finish

2030-03-31

Last updated by the study team

2026-07-10

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• STEP 1 REGISTRATION:
• Patient must be >= 18 years of age
• Patient must have biopsy-proven metastatic squamous cell carcinoma, originating in the oral cavity, larynx, oropharynx, or hypopharynx, with active disease present in both the head and neck and distant sites
• NOTE: The tumor from an oropharynx primary site must have known p16 status; p16 positive cancer of unknown primary is allowed as well, provided the disease presentation in consistent with a head and neck primary
• Patient can have prior surgical resection of a primary cancer in the head and neck at any previous time, however, residual/recurrent disease in the head and neck must be present on baseline imaging
• Any effects from prior cancer therapy for other diseases must be fully resolved and not pose a problem for giving the treatment on this trial
• Patient must have 4 or fewer metastatic sites prior to starting any treatment, with thoracic nodal disease considered a single site if encompassable in a tolerable radiotherapy hypofractionated field (i.e.,15 fractions or less)
• NOTE: Contiguous/adjacent metastases treatable in a single stereotactic field may be considered a single site
• NOTE: Patients with additional indeterminate findings such that the total number of metastatic sites would be more than 4 may be enrolled if a non-malignant etiology to these findings is a reasonable consideration
• Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
• Patients must have measurable disease as follows:
• For patients who have not started any initial systemic therapy (with pembrolizumab + chemotherapy) must have measurable disease documented by CT of the neck and chest, and abdomen obtained within 28 days prior to Step 1 registration
• For patients who have started or completed their 3 cycles of initial systemic therapy (with pembrolizumab + chemotherapy) must have measurable disease documented by CT of the neck, chest and abdomen obtained within 28 days prior to the start of their initial systemic therapy
• Leukocytes >= 3,000/mcL (obtained =< 28 days prior to Step 1 registration or prior to the start of any chemotherapy if on Arm T)
• Absolute neutrophil count (ANC) >= 1,500/mcL (obtained =< 28 days prior to Step 1 registration or prior to the start of any chemotherapy if on Arm T)
• Platelets >= 100,000/mcL (obtained =< 28 days prior to Step 1 registration or prior to the start of any chemotherapy if on Arm T)
• Total bilirubin =< institutional upper limit of normal (ULN). Patients with a total bilirubin > 1.5 x ULN, that is attributed to confirmed Gilbert's syndrome, are allowed after consultation and approval from their treating physician (obtained =< 28 days prior to Step 1 registration or prior to the start of any chemotherapy if on Arm T)
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) =< 3.0 x institutional ULN (obtained =< 28 days prior to Step 1 registration or prior to the start of any chemotherapy if on Arm T)
• Creatinine clearance: Glomerular filtration rate (GFR) >= 50 mL/min/1.73m\^2 (for patients receiving carboplatin-based regimens, GFR > 30 mL/min/1.73m\^2) (obtained =< 28 days prior to Step 1 registration or prior to the start of any chemotherapy if on Arm T)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of Step 1 registration are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better

You may not qualify if…

• Patients must not have prior head and neck radiotherapy
• Patient must not have an active autoimmune disease (i.e., inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, etc.) that has required systemic treatment (i.e., disease modifying agents, corticosteroids, or immunosuppressive drugs) in past 2 years. Replacement therapy (i.e., thyroxine, insulin, physiologic corticosteroid replacement) is not considered a form of systemic treatment and is allowed
• Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to Step 1 registration to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Patient must not have received any live vaccine within 30 days prior to Step 1 registration and while participating in the study. Live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, bacillus Calmette Guerin (BCG), and typhoid (oral) vaccine. Patients are permitted to receive inactivated vaccines and any non-live vaccines including those for the seasonal influenza and coronavirus disease 2019 (COVID-19) (Note: intranasal influenza vaccines, such as Flu-Mist trademark are live attenuated vaccines and are not allowed). If possible, it is recommended to separate study drug administration from vaccine administration by about a week (primarily, in order to minimize an overlap of adverse events

Where it is running

• Moffitt Cancer Center - McKinley Campus — Tampa, Florida, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• Emory University Hospital Midtown — Atlanta, Georgia, United States
• Saint Luke's Cancer Institute - Boise — Boise, Idaho, United States
• Saint Luke's Cancer Institute - Fruitland — Fruitland, Idaho, United States
• Saint Luke's Cancer Institute - Meridian — Meridian, Idaho, United States
• Saint Luke's Cancer Institute - Nampa — Nampa, Idaho, United States
• Saint Luke's Cancer Institute - Twin Falls — Twin Falls, Idaho, United States
• University of Illinois — Chicago, Illinois, United States
• Carle at The Riverfront — Danville, Illinois, United States
• Carle Physician Group-Effingham — Effingham, Illinois, United States
• Carle Physician Group-Mattoon/Charleston — Mattoon, Illinois, United States
• Carle Cancer Center — Urbana, Illinois, United States
• Mission Cancer and Blood - Ankeny — Ankeny, Iowa, United States
• Mercy Hospital — Cedar Rapids, Iowa, United States
• Oncology Associates at Mercy Medical Center — Cedar Rapids, Iowa, United States
• Iowa Methodist Medical Center — Des Moines, Iowa, United States
• Mission Cancer and Blood - Des Moines — Des Moines, Iowa, United States
• Sanford Joe Lueken Cancer Center — Bemidji, Minnesota, United States
• Freeman Health System — Joplin, Missouri, United States
• Sands Cancer Center — Canandiaqua, New York, United States
• Wilmot Cancer Institute Radiation Oncology at Greece — Rochester, New York, United States
• Highland Hospital — Rochester, New York, United States
• University of Rochester — Rochester, New York, United States
• Moffitt Cancer Center-International Plaza — Tampa, Florida, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.