Combining Radiation Therapy With Immunotherapy for the Treatment of Metastatic Squamous Cell Carcinoma of the Head and Neck
Study Purpose
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.
Recruitment Criteria
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
Eligible Ages | 18 Years and Over |
Gender | All |
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 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).
- - 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.
- - 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.
- - 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.
- - 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).
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.
- - 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.
- - Patient must not have received any live vaccine within 30 days prior to Step 1 registration and while participating in the study.
Trial Details
Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT05721755 |
Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 3 |
Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
ECOG-ACRIN Cancer Research Group |
Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
David J Sher |
Principal Investigator Affiliation | ECOG-ACRIN Cancer Research Group |
Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Other, NIH |
Overall Status | Recruiting |
Countries | United States |
Conditions
The disease, disorder, syndrome, illness, or injury that is being 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 |
PRIMARY OBJECTIVE:
- I. To compare overall survival (OS) between immunotherapy plus consolidative radiotherapy (CoRT) and immunotherapy alone following non-progression with systemic chemoimmunotherapy.
- 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.
- I. To compare the time-to-definitive-deterioration (TTDD) between the two arms.
- 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.
- III. To compare the time-to-deterioration (TTD) between the arms (first deterioration).
- 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.
- V. To compare quality-adjusted survival between the arms.
- 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.
- II. STEP II: Patients are randomized to 1 of 2 arms.
Arms
Experimental: 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.
Active Comparator: 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.
No Intervention: Arm S (no intervention)
Patients proceed directly to Step II.
Experimental: 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.
Interventions
Drug: - Carboplatin
Given IV
Drug: - Cisplatin
Given IV
Procedure: - Computed Tomography
Undergo CT and/or PET/CT
Drug: - Fluorouracil
Given IV
Procedure: - Magnetic Resonance Imaging
Undergo MRI
Drug: - Paclitaxel
Given IV
Biological: - Pembrolizumab
Given IV
Procedure: - Positron Emission Tomography
Undergo PET/CT
Other: - Quality-of-Life Assessment
Ancillary studies
Radiation: - Radiation Therapy
Undergo radiation therapy
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Recruiting
Address
Moffitt Cancer Center-International Plaza
Tampa 4174757, Florida 4155751, 33607
Status
Recruiting
Address
Moffitt Cancer Center - McKinley Campus
Tampa 4174757, Florida 4155751, 33612
Status
Recruiting
Address
Moffitt Cancer Center
Tampa 4174757, Florida 4155751, 33612
Status
Recruiting
Address
Emory University Hospital Midtown
Atlanta 4180439, Georgia 4197000, 30308
Status
Recruiting
Address
Saint Luke's Cancer Institute - Boise
Boise 5586437, Idaho 5596512, 83712
Status
Recruiting
Address
Saint Luke's Cancer Institute - Fruitland
Fruitland 5593708, Idaho 5596512, 83619
Status
Recruiting
Address
Saint Luke's Cancer Institute - Meridian
Meridian 5600685, Idaho 5596512, 83642
Status
Recruiting
Address
Saint Luke's Cancer Institute - Nampa
Nampa 5601933, Idaho 5596512, 83686
Status
Recruiting
Address
Saint Luke's Cancer Institute - Twin Falls
Twin Falls 5610810, Idaho 5596512, 83301
Status
Recruiting
Address
University of Illinois
Chicago 4887398, Illinois 4896861, 60612
Status
Recruiting
Address
Carle at The Riverfront
Danville 4889426, Illinois 4896861, 61832
Status
Recruiting
Address
Carle Physician Group-Effingham
Effingham 4237727, Illinois 4896861, 62401
Status
Recruiting
Address
Carle Physician Group-Mattoon/Charleston
Mattoon 4244099, Illinois 4896861, 61938
Status
Recruiting
Address
Carle Cancer Center
Urbana 4914570, Illinois 4896861, 61801
Status
Recruiting
Address
Mission Cancer and Blood - Ankeny
Ankeny 4846960, Iowa 4862182, 50023
Status
Recruiting
Address
Mercy Hospital
Cedar Rapids 4850751, Iowa 4862182, 52403
Status
Recruiting
Address
Oncology Associates at Mercy Medical Center
Cedar Rapids 4850751, Iowa 4862182, 52403
Status
Recruiting
Address
Iowa Methodist Medical Center
Des Moines 4853828, Iowa 4862182, 50309
Status
Recruiting
Address
Mission Cancer and Blood - Des Moines
Des Moines 4853828, Iowa 4862182, 50309
Status
Recruiting
Address
Sanford Joe Lueken Cancer Center
Bemidji 5017822, Minnesota 5037779, 56601
Status
Recruiting
Address
Freeman Health System
Joplin 4392768, Missouri 4398678, 64804
Status
Recruiting
Address
Sands Cancer Center
Canandiaqua, New York 5128638, 14424
Status
Recruiting
Address
Wilmot Cancer Institute Radiation Oncology at Greece
Rochester 5134086, New York 5128638, 14606
Status
Recruiting
Address
Highland Hospital
Rochester 5134086, New York 5128638, 14620
Status
Recruiting
Address
University of Rochester
Rochester 5134086, New York 5128638, 14642
Status
Recruiting
Address
Stony Brook University Medical Center
Stony Brook 5139865, New York 5128638, 11794
Status
Recruiting
Address
Wilmot Cancer Institute at Webster
Webster 5143495, New York 5128638, 14580
Status
Recruiting
Address
Sanford Bismarck Medical Center
Bismarck 5688025, North Dakota 5690763, 58501
Status
Recruiting
Address
Sanford Broadway Medical Center
Fargo 5059163, North Dakota 5690763, 58122
Status
Recruiting
Address
Sanford Roger Maris Cancer Center
Fargo 5059163, North Dakota 5690763, 58122
Status
Recruiting
Address
UH Seidman Cancer Center at UH Avon Health Center
Avon 5146277, Ohio 5165418, 44011
Status
Recruiting
Address
Case Western Reserve University
Cleveland 5150529, Ohio 5165418, 44106
Status
Recruiting
Address
UH Seidman Cancer Center at Lake Health Mentor Campus
Mentor 5162645, Ohio 5165418, 44060
Status
Recruiting
Address
University of Oklahoma Health Sciences Center
Oklahoma City 4544349, Oklahoma 4544379, 73104
Status
Recruiting
Address
Providence Newberg Medical Center
Newberg 5742726, Oregon 5744337, 97132
Status
Recruiting
Address
Providence Saint Vincent Medical Center
Portland 5746545, Oregon 5744337, 97225
Status
Recruiting
Address
Fox Chase Cancer Center
Philadelphia 4560349, Pennsylvania 6254927, 19111
Status
Recruiting
Address
Medical University of South Carolina
Charleston 4574324, South Carolina 4597040, 29425
Status
Recruiting
Address
Sanford Cancer Center Oncology Clinic
Sioux Falls 5231851, South Dakota 5769223, 57104
Status
Recruiting
Address
Sanford USD Medical Center - Sioux Falls
Sioux Falls 5231851, South Dakota 5769223, 57117-5134
Status
Recruiting
Address
VCU Massey Cancer Center at Stony Point
Richmond 4781708, Virginia 6254928, 23235
Status
Recruiting
Address
Virginia Commonwealth University/Massey Cancer Center
Richmond 4781708, Virginia 6254928, 23298
Status
Recruiting
Address
Langlade Hospital and Cancer Center
Antigo 5244010, Wisconsin 5279468, 54409
Status
Recruiting
Address
Gundersen Lutheran Medical Center
La Crosse 5258957, Wisconsin 5279468, 54601
Status
Recruiting
Address
ProHealth D N Greenwald Center
Mukwonago 5263965, Wisconsin 5279468, 53149
Status
Recruiting
Address
ProHealth Oconomowoc Memorial Hospital
Oconomowoc 5265499, Wisconsin 5279468, 53066
Status
Recruiting
Address
Ascension Saint Mary's Hospital
Rhinelander 5268720, Wisconsin 5279468, 54501
Status
Recruiting
Address
Ascension Saint Michael's Hospital
Stevens Point 5274644, Wisconsin 5279468, 54481
Status
Recruiting
Address
UW Cancer Center at ProHealth Care
Waukesha 5278052, Wisconsin 5279468, 53188
Status
Recruiting
Address
Aspirus Regional Cancer Center
Wausau 5278120, Wisconsin 5279468, 54401
Status
Recruiting
Address
Aspirus Cancer Care - Wisconsin Rapids
Wisconsin Rapids 5279436, Wisconsin 5279468, 54494