Testing What Happens When an Immunotherapy Drug (Pembrolizumab) is Given by Itself Compared to the Usual Treatment of Chemotherapy With Radiation After Surgery for Recurrent Head and Neck Squamous Cell Carcinoma

Recurrent Head and Neck Squamous Cell Carcinoma Clinical Trial

Official title:

A Phase II Randomized Trial of Adjuvant Therapy With Pembrolizumab After Resection of Recurrent/Second Primary Head and Neck Squamous Cell Carcinoma With High Risk Features

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04671667
• Other study ID #: NCI-2020-13174
• Secondary ID: NCI-2020-13174EA
• Status: Recruiting
• Phase: Phase 2
• Start date: April 27, 2021
• Est. completion date: February 28, 2026

Study information

• Verified date: March 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies the effect of pembrolizumab alone compared to the usual approach (chemotherapy [cisplatin and carboplatin] plus radiation therapy) after surgery in treating patients with head and neck squamous cell carcinoma that has come back (recurrent) or patients with a second head and neck cancer that is not from metastasis (primary). Radiation therapy uses high energy radiation or protons to kill tumor cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Carboplatin is also in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab alone after surgery may work better than the usual approach in shrinking recurrent or primary head and neck squamous cell carcinoma.

Description:

PRIMARY OBJECTIVE:

I. To evaluate overall survival (OS) of adjuvant pembrolizumab for 12 months compared to adjuvant reirradiation plus concurrent platinum chemotherapy in high risk head and neck squamous cell carcinoma (HNSCC) patients.

SECONDARY OBJECTIVES:

I. To evaluate the following endpoints in both arms: disease free survival (DFS), locoregional control, rates of distant metastasis, toxicity.

II. To evaluate whether high PD-L1 expression (defined as Combined Positive Score [CPS] >= 20) is predictive of increased efficacy in the experimental group compared to control.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM B: Patients receive cisplatin or carboplatin intravenously (IV) on day 1. Treatment repeats every 7 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo intensity-modulated radiation therapy (IMRT) or proton beam radiation therapy (PBRT) once daily (QD) for a total of 30 fractions in the absence of disease progression or unacceptable toxicity.

ARM C: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for 9 cycles in the absence of disease progression or unacceptable toxicity.

Patients in all arms undergo computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial.

After completion of study treatment, patients are followed up at 30 days, and then every 6 months for up to 5 years from the date of registration.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 188
• Est. completion date: February 28, 2026
• Est. primary completion date: February 28, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria:

• Patient must be between 18 and 79 years of age

• Patient must have locoregionally recurrent or second primary HNSCC (oral cavity, oropharynx, larynx, hypopharynx) in a previously radiated field

• Patient must have undergone surgery with gross total resection and must be randomized within 8 weeks of surgery

• Patients must have high risk disease defined as:

• Positive margins and/or extra nodal extension (ENE)

• Positive margins are defined as malignancy at or within 1 mm of the margin. High grade dysplasia (i.e. carcinoma in situ) at the margin is also considered positive

• ENE may be either gross or microscopic

• Patient must have a PD-L1 Combined Positive Score (CPS) >= 1 in a Clinical Laboratory Improvement Act (CLIA) certified laboratory. Testing can be done locally as long as it is done in a CLIA certified laboratory. This testing must be on the tumor specimen from the resection of the patient's recurrent or second primary HNSCC

• Patient must have had prior radiation to the area of recurrent or second primary tumor. This is defined as > 50% of the presurgical tumor volume having previously received a dose of > 45 Gy as determined by the treating radiation oncologist

• Patient must have completed prior radiation a minimum of 6 months prior to randomization

• Patient must not have any evidence of distant disease based on baseline imaging done within 28 days prior to randomization

• Patient must not have received anti-PD-1/PD-L1 therapy for recurrent disease. If the patient received anti-PD-1/PD-L1 therapy as part of initial upfront curative intent treatment (either as part of definitive non-surgical therapy or in the adjuvant setting) in the past, the last dosage of anti-PD-1/PD-L1 therapy must have been given greater than one year prior to randomization

• Patient must have an 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

• 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 randomization to rule out pregnancy. A urine or serum pregnancy test must be repeated within 72 hours prior to receiving the first dose of pembrolizumab or chemotherapy if the test done for eligibility/randomization is done outside of this 72 hour window. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 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 expect to conceive or father children by using by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse while on study treatment, and continue for 120 days after the last dose of study treatment

• Absolute neutrophil count (ANC) >= 1,500/mcL (obtained =< 28 days prior to protocol randomization)

• Platelets >= 100,000/mcL (obtained =< 28 days prior to protocol randomization)

• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (obtained =< 28 days prior to protocol randomization)

• 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 protocol randomization)

• Creatinine clearance > 30 ml/min using the Cockcroft-Gault formula (obtained =< 28 days prior to protocol randomization)

• Patient must not have a current active infection that requires systemic treatment at time of randomization

• Patient must not have a history of non-infectious pneumonitis requiring steroids within 3 years prior to randomization

• Patient must not have a history of solid organ transplant or stem cell transplant

• Patient must not be on immunosuppressive medication within 7 days prior to randomization, EXCEPT for the following: a) intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b) systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent; c) steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)

• 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 with New York Heart Association class III or IV heart failure are not eligible

• Patient must not have received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist [registered trademark]) are live attenuated vaccines and are not allowed

• Patient must not have severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients

• Patient must not have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed

• Patient must not have a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial as long as they have not been HIV-infected with a history of Kaposi sarcoma and/or multicentric Castleman disease

• Patient must not have a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection

• NOTE: No testing for hepatitis B and hepatitis C is required unless mandated by a local health authority

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Recurrence
• Recurrent Head and Neck Squamous Cell Carcinoma
• Recurrent Hypopharyngeal Squamous Cell Carcinoma
• Recurrent Laryngeal Squamous Cell Carcinoma
• Recurrent Oral Cavity Squamous Cell Carcinoma
• Recurrent Oropharyngeal Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Carboplatin
Given IV
• Cisplatin
Given IV

Procedure:
• Computed Tomography
Undergo CT

Radiation:
• Intensity-Modulated Radiation Therapy
Undergo IMRT

Procedure:
• Magnetic Resonance Imaging
Undergo MRI

Biological:
• Pembrolizumab
Given IV

Radiation:
• Proton Beam Radiation Therapy
Undergo PBRT

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	UPMC Altoona	Altoona	Pennsylvania
United States	Mission Cancer and Blood - Ankeny	Ankeny	Iowa
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	ThedaCare Regional Cancer Center	Appleton	Wisconsin
United States	Randolph Hospital	Asheboro	North Carolina
United States	Emory Proton Therapy Center	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Maryland Proton Treatment Center	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Tufts Medical Center	Boston	Massachusetts
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Medical University of South Carolina	Charleston	South Carolina
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Central Maryland Radiation Oncology in Howard County	Columbia	Maryland
United States	UM Sylvester Comprehensive Cancer Center at Coral Gables	Coral Gables	Florida
United States	Heartland Oncology and Hematology LLP	Council Bluffs	Iowa
United States	Methodist Jennie Edmundson Hospital	Council Bluffs	Iowa
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Carle at The Riverfront	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton Physician LLC - Englewood	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Premier Blood and Cancer Center	Dayton	Ohio
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mission Cancer and Blood - Des Moines	Des Moines	Iowa
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	HSHS Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	UM Baltimore Washington Medical Center/Tate Cancer Center	Glen Burnie	Maryland
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	Miami Valley Cancer Care and Infusion	Greenville	Ohio
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Kettering Medical Center	Kettering	Ohio
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Loyola University Medical Center	Maywood	Illinois
United States	Froedtert Menomonee Falls Hospital	Menomonee Falls	Wisconsin
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Community Medical Center	Missoula	Montana
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut
United States	Yale University	New Haven	Connecticut
United States	Mount Sinai Chelsea	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	Mount Sinai Union Square	New York	New York
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri
United States	HSHS Saint Elizabeth's Hospital	O'Fallon	Illinois
United States	Drexel Town Square Health Center	Oak Creek	Wisconsin
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Cancer Specialists/Oncology Hematology West PC - MECC	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Oncology Associates PC	Omaha	Nebraska
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	University of Kansas Hospital-Indian Creek Campus	Overland Park	Kansas
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Jefferson Torresdale Hospital	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UPMC-Passavant Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania
United States	UM Sylvester Comprehensive Cancer Center at Plantation	Plantation	Florida
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Annie Penn Memorial Hospital	Reidsville	North Carolina
United States	Reid Health	Richmond	Indiana
United States	VCU Massey Cancer Center at Stony Point	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	Sutter Roseville Medical Center	Roseville	California
United States	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Moffitt Cancer Center	Tampa	Florida
United States	Moffitt Cancer Center - McKinley Campus	Tampa	Florida
United States	Moffitt Cancer Center-International Plaza	Tampa	Florida
United States	Upper Valley Medical Center	Troy	Ohio
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Smilow Cancer Hospital Care Center - Waterford	Waterford	Connecticut
United States	Froedtert West Bend Hospital/Kraemer Cancer Center	West Bend	Wisconsin
United States	Methodist West Hospital	West Des Moines	Iowa
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	UPMC Memorial	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS)	Kaplan-Meier estimates will be used to estimate the OS distributions. A log-rank test with one-sided 10% type I error will be used for the comparison.	From randomization to date of death from any cause, measured at 2 years
Primary	Incidence of adverse events	Assessed using Common Terminology Criteria for Adverse Events. An 80% confidence interval around the hazard ratio of the two experimental arms will be calculated. Toxicity will be compared between the two treatment arms. Toxicity will be examined by arm and compared using the Fisher's exact test.	Up to 5 years from date of registration
Secondary	Disease free survival		From the date of randomization to the date of recurrence, second primary tumor from the head and neck region, or death, assessed up to 5 years from date of registration
Secondary	PD-L1 expression	Defined as Combined Positive Score >= 20 as a predictive marker of efficacy.	Up to 5 years from date of registration