Head and Neck Cancer

EA3191



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

STATUS: Active


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.
  • 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

United States
AL
Birmingham
University of Alabama at Birmingham Cancer Center
Contact: Site Public Contact
Email: tmyrick@uab.edu

AR
Little Rock
University of Arkansas for Medical Sciences
Contact: Site Public Contact

CA
Roseville
Sutter Cancer Centers Radiation Oncology Services-Roseville
Contact: Site Public Contact
Email: NCIclinicaltrials@sutterhealth.org

Sutter Roseville Medical Center
Contact: Site Public Contact
Email: NCIclinicaltrials@sutterhealth.org

CT
New Haven
Smilow Cancer Center/Yale-New Haven Hospital
Contact: Site Public Contact
Email: canceranswers@yale.edu

Yale University
Contact: Site Public Contact
Email: canceranswers@yale.edu

Trumbull
Smilow Cancer Hospital Care Center-Trumbull
Contact: Site Public Contact
Email: canceranswers@yale.edu

Waterford
Smilow Cancer Hospital Care Center - Waterford
Contact: Site Public Contact
Email: canceranswers@yale.edu

DC
Washington
MedStar Washington Hospital Center
Contact: Site Public Contact

FL
Coral Gables
UM Sylvester Comprehensive Cancer Center at Coral Gables
Contact: Site Public Contact

Deerfield Beach
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Contact: Site Public Contact

Gainesville
University of Florida Health Science Center - Gainesville
Contact: Site Public Contact
Email: cancer-center@ufl.edu

Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
Contact: Site Public Contact

Plantation
UM Sylvester Comprehensive Cancer Center at Plantation
Contact: Site Public Contact

Tampa
Moffitt Cancer Center
Contact: Site Public Contact
Email: ClinicalTrials@moffitt.org

Moffitt Cancer Center - McKinley Campus
Contact: Site Public Contact
Email: ClinicalTrials@moffitt.org

Moffitt Cancer Center-International Plaza
Contact: Site Public Contact
Email: ClinicalTrials@moffitt.org

GA
Atlanta
Emory Proton Therapy Center
Contact: Site Public Contact
Email: allyson.anderson@emory.edu

Emory University Hospital Midtown
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Emory University Hospital/Winship Cancer Institute
Contact: Site Public Contact

Savannah
Memorial Health University Medical Center
Contact: Site Public Contact
Email: Lorraine.OHara@hcahealthcare.com

IA
Ankeny
Mission Cancer and Blood - Ankeny
Contact: Site Public Contact

Council Bluffs
Heartland Oncology and Hematology LLP
Contact: Site Public Contact

Methodist Jennie Edmundson Hospital
Contact: Site Public Contact
Email: kathryn.bartz@nmhs.org

Des Moines
Broadlawns Medical Center
Contact: Site Public Contact

Iowa Lutheran Hospital
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Iowa Methodist Medical Center
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Medical Oncology and Hematology Associates-Des Moines
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West Des Moines
Methodist West Hospital
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IL
Chicago
John H Stroger Jr Hospital of Cook County
Contact: Site Public Contact

Northwestern University
Contact: Site Public Contact
Email: cancer@northwestern.edu

Danville
Carle at The Riverfront
Contact: Site Public Contact
Email: Research@Carle.com

DeKalb
Northwestern Medicine Cancer Center Kishwaukee
Contact: Site Public Contact
Email: Donald.Smith3@nm.org

Decatur
Cancer Care Specialists of Illinois - Decatur
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Email: morganthaler.jodi@mhsil.com

Decatur Memorial Hospital
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Email: morganthaler.jodi@mhsil.com

Effingham
Carle Physician Group-Effingham
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Email: Research@carle.com

Crossroads Cancer Center
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Email: morganthaler.jodi@mhsil.com

Geneva
Northwestern Medicine Cancer Center Delnor
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Email: Donald.Smith3@nm.org

Lake Forest
Northwestern Medicine Lake Forest Hospital
Contact: Site Public Contact
Email: cancertrials@northwestern.edu

Mattoon
Carle Physician Group-Mattoon/Charleston
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Email: Research@carle.com

Maywood
Loyola University Medical Center
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Springfield
Memorial Medical Center
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Email: pallante.beth@mhsil.com

Southern Illinois University School of Medicine
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Springfield Clinic
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Urbana
Carle Cancer Center
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Email: Research@carle.com

The Carle Foundation Hospital
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Email: Research@carle.com

Warrenville
Northwestern Medicine Cancer Center Warrenville
Contact: Site Public Contact
Email: Donald.Smith3@nm.org

IN
Richmond
Reid Health
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

KS
Kansas City
University of Kansas Cancer Center
Contact: Site Public Contact
Email: KUCC_Navigation@kumc.edu

Overland Park
University of Kansas Cancer Center-Overland Park
Contact: Site Public Contact
Email: KUCC_Navigation@kumc.edu

University of Kansas Hospital-Indian Creek Campus
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Email: KUCC_Navigation@kumc.edu

Westwood
University of Kansas Hospital-Westwood Cancer Center
Contact: Site Public Contact
Email: KUCC_Navigation@kumc.edu

KY
Lexington
University of Kentucky/Markey Cancer Center
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MA
Boston
Tufts Medical Center
Contact: Site Public Contact
Email: ContactUsCancerCenter@TuftsMedicalCenter.org

MD
Baltimore
Maryland Proton Treatment Center
Contact: Site Public Contact
Email: info@mdproton.com

University of Maryland/Greenebaum Cancer Center
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Columbia
Central Maryland Radiation Oncology in Howard County
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Glen Burnie
UM Baltimore Washington Medical Center/Tate Cancer Center
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MI
Ann Arbor
University of Michigan Comprehensive Cancer Center
Contact: Site Public Contact

Detroit
Wayne State University/Karmanos Cancer Institute
Contact: Site Public Contact
Email: ctoadmin@karmanos.org

Farmington Hills
Weisberg Cancer Treatment Center
Contact: Site Public Contact
Email: ctoadmin@karmanos.org

MN
Bemidji
Sanford Joe Lueken Cancer Center
Contact: Site Public Contact
Email: OncologyClinicalTrialsFargo@sanfordhealth.org

MO
Cape Girardeau
Saint Francis Medical Center
Contact: Site Public Contact
Email: sfmc@sfmc.net

Creve Coeur
Siteman Cancer Center at West County Hospital
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Kansas City
University of Kansas Cancer Center - North
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Email: KUCC_Navigation@kumc.edu

Lee's Summit
University of Kansas Cancer Center - Lee's Summit
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Email: KUCC_Navigation@kumc.edu

North Kansas City
University of Kansas Cancer Center at North Kansas City Hospital
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Email: KUCC_Navigation@kumc.edu

Saint Louis
Siteman Cancer Center at Christian Hospital
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Siteman Cancer Center-South County
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Email: info@siteman.wustl.edu

Washington University School of Medicine
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Email: info@siteman.wustl.edu

Saint Peters
Siteman Cancer Center at Saint Peters Hospital
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Email: info@siteman.wustl.edu

Springfield
Mercy Hospital Springfield
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MS
Jackson
University of Mississippi Medical Center
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MT
Great Falls
Benefis Healthcare- Sletten Cancer Institute
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Kalispell
Kalispell Regional Medical Center
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Missoula
Community Medical Hospital
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Email: mccinfo@mtcancer.org

NC
Asheboro
Randolph Hospital
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Greensboro
Cone Health Cancer Center
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Email: stacey.phelps@conehealth.com

Reidsville
Annie Penn Memorial Hospital
Contact: Site Public Contact
Email: stacey.phelps@conehealth.com

ND
Bismarck
Sanford Bismarck Medical Center
Contact: Site Public Contact
Email: OncologyClinicalTrialsFargo@sanfordhealth.org

Fargo
Sanford Roger Maris Cancer Center
Contact: Site Public Contact
Email: OncologyClinicalTrialsFargo@sanfordhealth.org

NE
Omaha
Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
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Nebraska Methodist Hospital
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Oncology Associates PC
Contact: Site Public Contact
Email: info@oa-oc.com

NM
Albuquerque
University of New Mexico Cancer Center
Contact: Site Public Contact
Email: HSC-ClinicalTrialInfo@salud.unm.edu

NY
New York
Mount Sinai Chelsea
Contact: Site Public Contact
Email: CCTO@mssm.edu

Mount Sinai Hospital
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Email: CCTO@mssm.edu

Mount Sinai Union Square
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Email: CCTO@mssm.edu

Stony Brook
Stony Brook University Medical Center
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OH
Centerville
Dayton Physicians LLC-Miami Valley South
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Miami Valley Hospital South
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Email: clinical.trials@daytonncorp.org

Cleveland
Cleveland Clinic Foundation
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Email: TaussigResearch@ccf.org

Dayton
Dayton Blood and Cancer Center
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Dayton Physician LLC-Miami Valley Hospital North
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Email: clinical.trials@daytonncorp.org

Miami Valley Hospital North
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Email: clinical.trials@daytonncorp.org

Franklin
Dayton Physicians LLC-Atrium
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Email: clinical.trials@daytonncorp.org

Kettering
Greater Dayton Cancer Center
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Email: clinical.trials@daytonncorp.org

Kettering Medical Center
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Email: clinical.trials@daytonncorp.org

OK
Lawton
Cancer Centers of Southwest Oklahoma Research
Contact: Site Public Contact

Oklahoma City
University of Oklahoma Health Sciences Center
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Email: ou-clinical-trials@ouhsc.edu

OR
Clackamas
Clackamas Radiation Oncology Center
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

Providence Cancer Institute Clackamas Clinic
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Email: CanRsrchStudies@providence.org

Newberg
Providence Newberg Medical Center
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Email: CanRsrchStudies@providence.org

Portland
Providence Portland Medical Center
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Email: CanRsrchStudies@providence.org

Providence Saint Vincent Medical Center
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Email: CanRsrchStudies@providence.org

PA
Altoona
UPMC Altoona
Contact: Site Public Contact
Email: ecog.rss@jimmy.harvard.edu

Danville
Geisinger Medical Center
Contact: Site Public Contact
Email: HemonCCTrials@geisinger.edu

Lewisburg
Geisinger Medical Oncology-Lewisburg
Contact: Site Public Contact
Email: HemonCCTrials@geisinger.edu

Philadelphia
Fox Chase Cancer Center
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Jefferson Torresdale Hospital
Contact: Site Public Contact
Email: ONCTrialNow@jefferson.edu

Temple University Hospital
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Thomas Jefferson University Hospital
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Email: ONCTrialNow@jefferson.edu

Pittsburgh
UPMC-Passavant Hospital
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UPMC-Shadyside Hospital
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University of Pittsburgh Cancer Institute (UPCI)
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Wilkes-Barre
Geisinger Wyoming Valley/Henry Cancer Center
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Email: HemonCCTrials@geisinger.edu

York
UPMC Memorial
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SC
Charleston
Medical University of South Carolina
Contact: Site Public Contact
Email: hcc-clinical-trials@musc.edu

SD
Sioux Falls
Avera Cancer Institute
Contact: Site Public Contact
Email: OncRegulatory@avera.org

Sanford USD Medical Center - Sioux Falls
Contact: Site Public Contact
Email: OncologyClinicalTrialsSF@SanfordHealth.org

TN
Nashville
Vanderbilt University/Ingram Cancer Center
Contact: Site Public Contact

UT
Salt Lake City
Huntsman Cancer Institute/University of Utah
Contact: Site Public Contact
Email: cancerinfo@hci.utah.edu

VA
Richmond
VCU Massey Cancer Center at Stony Point
Contact: Site Public Contact
Email: ctoclinops@vcu.edu

Virginia Commonwealth University/Massey Cancer Center
Contact: Site Public Contact
Email: CTOclinops@vcu.edu

WI
Appleton
ThedaCare Regional Cancer Center
Contact: Site Public Contact
Email: ResearchDept@thedacare.org

Eau Claire
HSHS Sacred Heart Hospital
Contact: Site Public Contact
Email: ewd_research_admin@hshs.org

Green Bay
Saint Vincent Hospital Cancer Center Green Bay
Contact: Site Public Contact
Email: ewd_research_admin@hshs.org

Saint Vincent Hospital Cancer Center at Saint Mary's
Contact: Site Public Contact
Email: ewd_research_admin@hshs.org

Menomonee Falls
Froedtert Menomonee Falls Hospital
Contact: Site Public Contact

Milwaukee
Medical College of Wisconsin
Contact: Site Public Contact

Oak Creek
Drexel Town Square Health Center
Contact: Site Public Contact

Sturgeon Bay
Saint Vincent Hospital Cancer Center at Sturgeon Bay
Contact: Site Public Contact
Email: ewd_research_admin@hshs.org

West Bend
Froedtert West Bend Hospital/Kraemer Cancer Center
Contact: Site Public Contact

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.

Interactive content above is from the official study record on the National Cancer Institute website, cancer.gov.


The ECOG-ACRIN Cancer Research Group designed this trial and is conducting it with funding from the National Cancer Institute through its National Clinical Trials Network.


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ECOG-ACRIN Cancer Research Group