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

NCT05721755 | Active Not Recruiting Phase 3 FDA Drug

• 3 other identifiers: EA3211NCI-2022-10141U10CA180820
• Study Type: interventional
• Target: 290
• Locations: 1 country
• Sites: 51

Brief Summary

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.

Conditions

Metastatic Head and Neck Squamous Cell Carcinoma; Metastatic Hypopharyngeal Squamous Cell Carcinoma; Metastatic Oral Cavity 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; Metastatic Laryngeal Squamous Cell Carcinoma; Metastatic Oropharyngeal Squamous Cell Carcinoma; Stage IV Lip and Oral Cavity Cancer AJCC v8; Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8; Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Time from step 2 randomization to death from any cause, assessed up to 3 years

Secondary Outcomes (3)

• Progression-free survival

  Time from step 2 randomization to disease progression or death, assessed up to 3 years

• Time to treatment failure

  Time from step 2 randomization to the cessation of immunotherapy due to progression, treatment-related toxicity, or death, assessed up to 3 years

• Incidence of adverse events (AE)

  Up to 3 years

Other Outcomes (7)

• Patterns-of-failure with respect to local, regional and distant recurrences

  Up to 3 years

• Incidence of tracheostomy and/or gastrostomy

  At any point during treatment, assessed up to 3 years

• Time-to-definitive-deterioration

  At 60 weeks post-baseline

Study Arms (4)

Arm A (pembrolizumab and radiation)

EXPERIMENTAL

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.

Drug: Carboplatin; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Fluorouracil; Procedure: Magnetic Resonance Imaging; Drug: Paclitaxel; Biological: Pembrolizumab; Procedure: Positron Emission Tomography; Other: Quality-of-Life Assessment; Radiation: Radiation Therapy

Arm B (pembrolizumab monotherapy)

ACTIVE COMPARATOR

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.

Drug: Carboplatin; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Fluorouracil; Procedure: Magnetic Resonance Imaging; Drug: Paclitaxel; Biological: Pembrolizumab; Procedure: Positron Emission Tomography; Other: Quality-of-Life Assessment

Arm S (no intervention)

NO INTERVENTION

Patients proceed directly to Step II.

Arm T (pembrolizumab, chemotherapy)

EXPERIMENTAL

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.

Drug: Carboplatin; Drug: Cisplatin; Drug: Fluorouracil; Drug: Paclitaxel; Biological: Pembrolizumab

Interventions

Computed Tomography PROCEDURE

Undergo CT and/or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Arm A (pembrolizumab and radiation); Arm B (pembrolizumab monotherapy)

Fluorouracil DRUG

Given IV

Also known as: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-Fu, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Arm A (pembrolizumab and radiation); Arm B (pembrolizumab monotherapy); Arm T (pembrolizumab, chemotherapy)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Arm A (pembrolizumab and radiation); Arm B (pembrolizumab monotherapy)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Arm A (pembrolizumab and radiation); Arm B (pembrolizumab monotherapy); Arm T (pembrolizumab, chemotherapy)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Arm A (pembrolizumab and radiation); Arm B (pembrolizumab monotherapy); Arm T (pembrolizumab, chemotherapy)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Arm A (pembrolizumab and radiation); Arm B (pembrolizumab monotherapy)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm A (pembrolizumab and radiation); Arm B (pembrolizumab monotherapy)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Arm A (pembrolizumab and radiation)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Arm A (pembrolizumab and radiation); Arm B (pembrolizumab monotherapy); Arm T (pembrolizumab, chemotherapy)

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Arm A (pembrolizumab and radiation); Arm B (pembrolizumab monotherapy); Arm T (pembrolizumab, chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

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

Sponsors & Collaborators

• ECOG-ACRIN Cancer Research Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (51)

Moffitt Cancer Center-International Plaza

Tampa, Florida, 33607, United States

Location

Moffitt Cancer Center - McKinley Campus

Tampa, Florida, 33612, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Saint Luke's Cancer Institute - Boise

Boise, Idaho, 83712, United States

Location

Saint Luke's Cancer Institute - Fruitland

Fruitland, Idaho, 83619, United States

Location

Saint Luke's Cancer Institute - Meridian

Meridian, Idaho, 83642, United States

Location

Saint Luke's Cancer Institute - Nampa

Nampa, Idaho, 83686, United States

Location

Saint Luke's Cancer Institute - Twin Falls

Twin Falls, Idaho, 83301, United States

Location

University of Illinois

Chicago, Illinois, 60612, United States

Location

Carle at The Riverfront

Danville, Illinois, 61832, United States

Location

Carle Physician Group-Effingham

Effingham, Illinois, 62401, United States

Location

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois, 61938, United States

Location

Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Mission Cancer and Blood - Ankeny

Ankeny, Iowa, 50023, United States

Location

Mercy Hospital

Cedar Rapids, Iowa, 52403, United States

Location

Oncology Associates at Mercy Medical Center

Cedar Rapids, Iowa, 52403, United States

Location

Iowa Methodist Medical Center

Des Moines, Iowa, 50309, United States

Location

Mission Cancer and Blood - Des Moines

Des Moines, Iowa, 50309, United States

Location

Sanford Joe Lueken Cancer Center

Bemidji, Minnesota, 56601, United States

Location

Freeman Health System

Joplin, Missouri, 64804, United States

Location

Sands Cancer Center

Canandiaqua, New York, 14424, United States

Location

Wilmot Cancer Institute Radiation Oncology at Greece

Rochester, New York, 14606, United States

Location

Highland Hospital

Rochester, New York, 14620, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

Wilmot Cancer Institute at Webster

Webster, New York, 14580, United States

Location

Sanford Bismarck Medical Center

Bismarck, North Dakota, 58501, United States

Location

Sanford Broadway Medical Center

Fargo, North Dakota, 58122, United States

Location

Sanford Roger Maris Cancer Center

Fargo, North Dakota, 58122, United States

Location

UH Seidman Cancer Center at UH Avon Health Center

Avon, Ohio, 44011, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

UH Seidman Cancer Center at Lake Health Mentor Campus

Mentor, Ohio, 44060, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Providence Newberg Medical Center

Newberg, Oregon, 97132, United States

Location

Providence Saint Vincent Medical Center

Portland, Oregon, 97225, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota, 57104, United States

Location

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, 57117-5134, United States

Location

VCU Massey Cancer Center at Stony Point

Richmond, Virginia, 23235, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Langlade Hospital and Cancer Center

Antigo, Wisconsin, 54409, United States

Location

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, 54601, United States

Location

ProHealth D N Greenwald Center

Mukwonago, Wisconsin, 53149, United States

Location

ProHealth Oconomowoc Memorial Hospital

Oconomowoc, Wisconsin, 53066, United States

Location

Ascension Saint Mary's Hospital

Rhinelander, Wisconsin, 54501, United States

Location

Ascension Saint Michael's Hospital

Stevens Point, Wisconsin, 54481, United States

Location

UW Cancer Center at ProHealth Care

Waukesha, Wisconsin, 53188, United States

Location

Aspirus Regional Cancer Center

Wausau, Wisconsin, 54401, United States

Location

Aspirus Cancer Care - Wisconsin Rapids

Wisconsin Rapids, Wisconsin, 54494, United States

Location

MeSH Terms

Conditions

Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Mouth Neoplasms; Carcinoma

Interventions

Carboplatin; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Fluorouracil; dehydroftorafur; Magnetic Resonance Spectroscopy; Paclitaxel; Taxes; pembrolizumab; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Carcinoma, Squamous Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Mouth Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Therapeutics; Physical Phenomena

Study Officials

• David J Sher

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2023
• First Posted: February 10, 2023
• Study Start: June 8, 2023
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): March 31, 2030
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (51)