Radiation plus immunotherapy: a new hope for advanced head and neck cancer?
NCT ID NCT05721755
First seen Jun 26, 2026 · Last updated Sep 15, 2026 · Updated 4 times
Summary
This phase III trial compares the standard immunotherapy drug pembrolizumab alone versus pembrolizumab plus radiation therapy in 290 patients with metastatic head and neck cancer. The goal is to see if adding radiation improves overall survival. Participants receive pembrolizumab with chemotherapy first, then are randomly assigned to continue pembrolizumab with or without radiation.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- pembrolizumab (immunotherapy) plus radiation therapy
- What this could lead to
- If it works, this could become a new standard treatment that improves survival for people with metastatic head and neck cancer.
- What could go wrong
- This is a phase III trial, but results are not yet available. Adding radiation may increase side effects without improving outcomes.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
-
Phase 3
Large-scale testing in a bigger group. Usually the last step before a treatment can be approved.
- Participants
-
About 290 people
The number the study aims to enrol. It can still change while the study runs.
- Started
-
Jun 2023
- Expected to finish
-
Mar 2030
An estimate. End dates often move.
- Lead sponsor
-
A research network
The lead sponsor is a research network or cooperative group.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
-
18 years and older
- Sex
-
Anyone
- Healthy volunteers
-
Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Inclusion Criteria: * 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 * Patients on Arm S must have received chemoimmunotherapy * Patients will be enrolled in the quality of life (QOL) study if the patient can read and understand English, Spanish, French or Chinese (simplified or traditional characters) * NOTE: Sites cannot translate the associated QOL forms * Patients of childbearing potential and/or sexually active patients must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. Patients of childbearing potential must continue contraceptive measures for 4 months after the last dose of protocol treatment and must not breastfeed while on study treatment through 4 months after the last dose of protocol treatment * STEP 2 RANDOMIZATION: * Patient must have ECOG performance status 0-2 * Patient must have completed 3 cycles of initial systemic chemotherapy * For patients registered to Arm S on Step 1, patients must have at least stable disease after completing 3 cycles of pembrolizumab + chemotherapy * Patient must have no signs of progression (complete response \[CR\]/partial response \[PR\] or stable disease \[SD\]) on restaging imaging (consisting of neck, chest, and abdomen CT). Restaging imaging must have been done after completion of initial systemic chemotherapy with pembrolizumab + chemotherapy on Step 1 and within 7 days prior to step 2 randomization. Patients with stable or responding radiologic response are eligible for Step 2 Exclusion Criteria: * 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
Get updates
Get notified about this study
Sign up to get updates when this study changes or when new studies for Clinical stage IV HPV-mediated (P16-positive) oropharyngeal carcinoma ajcc V8 are added.
Genom att skicka in godkänner du våra Användarvillkor
Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
Contacts and locations
Locations
-
Ascension Saint Mary's Hospital
Rhinelander, Wisconsin, 54501, United States
-
Ascension Saint Michael's Hospital
Stevens Point, Wisconsin, 54481, United States
-
Aspirus Cancer Care - Wisconsin Rapids
Wisconsin Rapids, Wisconsin, 54494, United States
-
Aspirus Regional Cancer Center
Wausau, Wisconsin, 54401, United States
-
Carle Cancer Center
Urbana, Illinois, 61801, United States
-
Carle Physician Group-Effingham
Effingham, Illinois, 62401, United States
-
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938, United States
-
Carle at The Riverfront
Danville, Illinois, 61832, United States
-
Case Western Reserve University
Cleveland, Ohio, 44106, United States
-
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
-
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
-
Freeman Health System
Joplin, Missouri, 64804, United States
-
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601, United States
-
Highland Hospital
Rochester, New York, 14620, United States
-
Iowa Methodist Medical Center
Des Moines, Iowa, 50309, United States
-
Langlade Hospital and Cancer Center
Antigo, Wisconsin, 54409, United States
-
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
-
Mercy Hospital
Cedar Rapids, Iowa, 52403, United States
-
Mission Cancer and Blood - Ankeny
Ankeny, Iowa, 50023, United States
-
Mission Cancer and Blood - Des Moines
Des Moines, Iowa, 50309, United States
-
Moffitt Cancer Center
Tampa, Florida, 33612, United States
-
Moffitt Cancer Center - McKinley Campus
Tampa, Florida, 33612, United States
-
Moffitt Cancer Center-International Plaza
Tampa, Florida, 33607, United States
-
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, 52403, United States
-
ProHealth D N Greenwald Center
Mukwonago, Wisconsin, 53149, United States
-
ProHealth Oconomowoc Memorial Hospital
Oconomowoc, Wisconsin, 53066, United States
-
Providence Newberg Medical Center
Newberg, Oregon, 97132, United States
-
Providence Saint Vincent Medical Center
Portland, Oregon, 97225, United States
-
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712, United States
-
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619, United States
-
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, 83642, United States
-
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, 83686, United States
-
Saint Luke's Cancer Institute - Twin Falls
Twin Falls, Idaho, 83301, United States
-
Sands Cancer Center
Canandiaqua, New York, 14424, United States
-
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501, United States
-
Sanford Broadway Medical Center
Fargo, North Dakota, 58122, United States
-
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota, 57104, United States
-
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, 56601, United States
-
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122, United States
-
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
-
Stony Brook University Medical Center
Stony Brook, New York, 11794, United States
-
UH Seidman Cancer Center at Lake Health Mentor Campus
Mentor, Ohio, 44060, United States
-
UH Seidman Cancer Center at UH Avon Health Center
Avon, Ohio, 44011, United States
-
UW Cancer Center at ProHealth Care
Waukesha, Wisconsin, 53188, United States
-
University of Illinois
Chicago, Illinois, 60612, United States
-
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
-
University of Rochester
Rochester, New York, 14642, United States
-
VCU Massey Cancer Center at Stony Point
Richmond, Virginia, 23235, United States
-
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298, United States
-
Wilmot Cancer Institute Radiation Oncology at Greece
Rochester, New York, 14606, United States
-
Wilmot Cancer Institute at Webster
Webster, New York, 14580, United States
More trials for these conditions
Other studies related to the condition(s) this trial covers.
- Can a new drug combo slow advanced head and neck cancer?
- Can a Three-Pronged attack shrink Hard-to-Treat head and neck cancers?
- Leftover immunotherapy may boost chemo: new study investigates timing
- Can a smaller dose of this cancer drug still work? new trial aims to find out
- Remote hearing tests could save cancer Patients' hearing
- Could an antidepressant ease cancer treatment pain? new study investigates