RECRUITING

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

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Phase III Randomized Trial of Immunotherapy With or Without Consolidative Radiotherapy for Oligometastatic Head and Neck Squamous Cell Carcinoma

Quick Facts

Study Start:2023-06-08

Study Completion:2030-03-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05721755

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Principal Investigator

David J Sher

PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Study Locations (Sites)

Moffitt Cancer Center-International Plaza

Tampa, Florida, 33607

United States

Moffitt Cancer Center - McKinley Campus

Tampa, Florida, 33612

United States

Moffitt Cancer Center

Tampa, Florida, 33612

United States

Emory University Hospital Midtown

Atlanta, Georgia, 30308

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

University of Illinois

Chicago, Illinois, 60612

United States

Carle at The Riverfront

Danville, Illinois, 61832

United States

Carle Physician Group-Effingham

Effingham, Illinois, 62401

United States

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois, 61938

United States

Carle Cancer Center

Urbana, Illinois, 61801

United States

Mission Cancer and Blood - Ankeny

Ankeny, Iowa, 50023

United States

Mercy Hospital

Cedar Rapids, Iowa, 52403

United States

Oncology Associates at Mercy Medical Center

Cedar Rapids, Iowa, 52403

United States

Iowa Methodist Medical Center

Des Moines, Iowa, 50309

United States

Mission Cancer and Blood - Des Moines

Des Moines, Iowa, 50309

United States

Sanford Joe Lueken Cancer Center

Bemidji, Minnesota, 56601

United States

Freeman Health System

Joplin, Missouri, 64804

United States

Sands Cancer Center

Canandaigua, New York, 14424

United States

Wilmot Cancer Institute Radiation Oncology at Greece

Rochester, New York, 14606

United States

Highland Hospital

Rochester, New York, 14620

United States

University of Rochester

Rochester, New York, 14642

United States

Stony Brook University Medical Center

Stony Brook, New York, 11794

United States

Wilmot Cancer Institute at Webster

Webster, New York, 14580

United States

Sanford Bismarck Medical Center

Bismarck, North Dakota, 58501

United States

Sanford Broadway Medical Center

Fargo, North Dakota, 58122

United States

Sanford Roger Maris Cancer Center

Fargo, North Dakota, 58122

United States

UH Seidman Cancer Center at UH Avon Health Center

Avon, Ohio, 44011

United States

Case Western Reserve University

Cleveland, Ohio, 44106

United States

UH Seidman Cancer Center at Lake Health Mentor Campus

Mentor, Ohio, 44060

United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104

United States

Providence Newberg Medical Center

Newberg, Oregon, 97132

United States

Providence Saint Vincent Medical Center

Portland, Oregon, 97225

United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111

United States

Medical University of South Carolina

Charleston, South Carolina, 29425

United States

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota, 57104

United States

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, 57117-5134

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

Langlade Hospital and Cancer Center

Antigo, Wisconsin, 54409

United States

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, 54601

United States

ProHealth D N Greenwald Center

Mukwonago, Wisconsin, 53149

United States

ProHealth Oconomowoc Memorial Hospital

Oconomowoc, Wisconsin, 53066

United States

Ascension Saint Mary's Hospital

Rhinelander, Wisconsin, 54501

United States

Ascension Saint Michael's Hospital

Stevens Point, Wisconsin, 54481

United States

UW Cancer Center at ProHealth Care

Waukesha, Wisconsin, 53188

United States

Aspirus Regional Cancer Center

Wausau, Wisconsin, 54401

United States

Aspirus Cancer Care - Wisconsin Rapids

Wisconsin Rapids, Wisconsin, 54494

United States

Collaborators and Investigators

Sponsor: ECOG-ACRIN Cancer Research Group

David J Sher, PRINCIPAL_INVESTIGATOR, ECOG-ACRIN Cancer Research Group

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-06-08

Study Completion Date2030-03-31

Study Record Updates

Study Start Date2023-06-08

Study Completion Date2030-03-31

Terms related to this study

Additional Relevant MeSH Terms

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