Combining Radiation Therapy With Immunotherapy for the Treatment of Metastatic Squamous Cell Carcinoma of the Head and Neck
NCT ID: NCT05721755
Last Updated: 2025-11-13
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE3
290 participants
INTERVENTIONAL
2023-06-08
2030-03-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
I. To compare overall survival (OS) between immunotherapy plus consolidative radiotherapy (CoRT) and immunotherapy alone following non-progression with systemic chemoimmunotherapy.
SECONDARY OBJECTIVES:
I. To compare progression-free survival (PFS) between the two arms. II. To compare time-to-treatment failure (TTF) between the two arms. III. To determine the risk of non-hematologic high-grade (3 or higher) toxicity with the addition of CoRT.
IV. To establish the prognostic value of quantitative positron emission tomography (PET) biomarkers at baseline (standardized uptake value maximum \[SUVmax\], metabolic tumor volume \[MTV\], total lesion glycolysis \[TLG\]) for overall survival in both arms.
V. To establish the predictive value of (a) structured qualitative read (Hopkins Criteria) and (b) quantitative analysis for assessment of the post-radiotherapy or chemotherapy restaging PET/computed tomography (CT) to evaluate its association with overall survival in both arms.
HEALTH-RELATED QUALITY-OF-LIFE (HRQL) OBJECTIVES:
I. To compare the time-to-definitive-deterioration (TTDD) between the two arms. (PRIMARY) II. To compare the mean early change in the Functional Assessment of Cancer Therapy - Head \& Neck (FACT-HN) trial outcome index (TOI) between the arms, defined as the difference between the cycle 7 time point and randomization. (SECONDARY) III. To compare the time-to-deterioration (TTD) between the arms (first deterioration). (SECONDARY) IV. To compare the nadir of the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM) score over the course of study participation between the arms. (EXPLORATORY) V. To compare quality-adjusted survival between the arms. (EXPLORATORY)
EXPLORATORY OBJECTIVES:
I. To identify differences in patterns-of-failure with respect to local regional and distant recurrences following CoRT versus immunotherapy alone.
II. To evaluate the risk of tracheostomy and/or gastrostomy in patients treated with CoRT versus immunotherapy alone.
OUTLINE:
STEP 1: Patients who have not completed initial systemic therapy prior to enrollment are assigned to Arm T and patients who have completed initial systemic therapy prior to enrollment are assigned to Arm S.
ARM T: Patients receive pembrolizumab intravenously (IV) with carboplatin IV and paclitaxel IV, or with cisplatin IV and fluorouracil IV, or with carboplatin IV and fluorouracil IV on study.
ARM S: Patients proceed directly to Step II.
STEP II: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive one cycle of pembrolizumab IV with carboplatin IV and paclitaxel IV, or with cisplatin IV and fluorouracil IV, or with carboplatin IV, and fluorouracil IV on study and then receive pembrolizumab IV with radiation therapy on study. Patients also undergo CT, PET/CT, and/or magnetic resonance imaging (MRI) throughout the trial.
ARM B: Patients receive one cycle of pembrolizumab IV with carboplatin IV and paclitaxel IV, or with cisplatin IV and fluorouracil IV, or with carboplatin IV, and fluorouracil IV on study and then receive pembrolizumab IV monotherapy on study. Patients also undergo CT, PET/CT, and/or MRI throughout the trial.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm A (pembrolizumab and radiation)
Patients receive one cycle of pembrolizumab IV with carboplatin IV and paclitaxel IV, or with cisplatin IV and fluorouracil IV, or with carboplatin IV, and fluorouracil IV on study and then receive pembrolizumab IV with radiation therapy on study. Patients also undergo CT, PET/CT, and/or MRI throughout the trial.
Carboplatin
Given IV
Cisplatin
Given IV
Computed Tomography
Undergo CT and/or PET/CT
Fluorouracil
Given IV
Magnetic Resonance Imaging
Undergo MRI
Paclitaxel
Given IV
Pembrolizumab
Given IV
Positron Emission Tomography
Undergo PET/CT
Quality-of-Life Assessment
Ancillary studies
Radiation Therapy
Undergo radiation therapy
Arm B (pembrolizumab monotherapy)
Patients receive one cycle of pembrolizumab IV with carboplatin IV and paclitaxel IV, or with cisplatin IV and fluorouracil IV, or with carboplatin IV, and fluorouracil IV on study and then receive pembrolizumab IV monotherapy on study. Patients also undergo CT, PET/CT, and/or MRI throughout the trial.
Carboplatin
Given IV
Cisplatin
Given IV
Computed Tomography
Undergo CT and/or PET/CT
Fluorouracil
Given IV
Magnetic Resonance Imaging
Undergo MRI
Paclitaxel
Given IV
Pembrolizumab
Given IV
Positron Emission Tomography
Undergo PET/CT
Quality-of-Life Assessment
Ancillary studies
Arm S (no intervention)
Patients proceed directly to Step II.
No interventions assigned to this group
Arm T (pembrolizumab, chemotherapy)
Patients receive pembrolizumab IV with carboplatin IV and paclitaxel IV, or with cisplatin IV and fluorouracil IV, or with carboplatin IV and fluorouracil IV on study.
Carboplatin
Given IV
Cisplatin
Given IV
Fluorouracil
Given IV
Paclitaxel
Given IV
Pembrolizumab
Given IV
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Carboplatin
Given IV
Cisplatin
Given IV
Computed Tomography
Undergo CT and/or PET/CT
Fluorouracil
Given IV
Magnetic Resonance Imaging
Undergo MRI
Paclitaxel
Given IV
Pembrolizumab
Given IV
Positron Emission Tomography
Undergo PET/CT
Quality-of-Life Assessment
Ancillary studies
Radiation Therapy
Undergo radiation therapy
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
ECOG-ACRIN Cancer Research Group
NETWORK
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
David J Sher
Role: PRINCIPAL_INVESTIGATOR
ECOG-ACRIN Cancer Research Group
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Moffitt Cancer Center-International Plaza
Tampa, Florida, United States
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
Stony Brook University Medical Center
Stony Brook, New York, United States
Wilmot Cancer Institute at Webster
Webster, New York, United States
Sanford Bismarck Medical Center
Bismarck, North Dakota, United States
Sanford Broadway Medical Center
Fargo, North Dakota, United States
Sanford Roger Maris Cancer Center
Fargo, North Dakota, United States
UH Seidman Cancer Center at UH Avon Health Center
Avon, Ohio, United States
Case Western Reserve University
Cleveland, Ohio, United States
UH Seidman Cancer Center at Lake Health Mentor Campus
Mentor, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Providence Newberg Medical Center
Newberg, Oregon, United States
Providence Saint Vincent Medical Center
Portland, Oregon, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, United States
VCU Massey Cancer Center at Stony Point
Richmond, Virginia, United States
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States
Langlade Hospital and Cancer Center
Antigo, Wisconsin, United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, United States
ProHealth D N Greenwald Center
Mukwonago, Wisconsin, United States
ProHealth Oconomowoc Memorial Hospital
Oconomowoc, Wisconsin, United States
Ascension Saint Mary's Hospital
Rhinelander, Wisconsin, United States
Ascension Saint Michael's Hospital
Stevens Point, Wisconsin, United States
UW Cancer Center at ProHealth Care
Waukesha, Wisconsin, United States
Aspirus Regional Cancer Center
Wausau, Wisconsin, United States
Aspirus Cancer Care - Wisconsin Rapids
Wisconsin Rapids, Wisconsin, United States
Countries
Review the countries where the study has at least one active or historical site.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2022-10141
Identifier Type: REGISTRY
Identifier Source: secondary_id
EA3211
Identifier Type: OTHER
Identifier Source: secondary_id
EA3211
Identifier Type: OTHER
Identifier Source: secondary_id
EA3211
Identifier Type: -
Identifier Source: org_study_id