Head and Neck Cancer

EA3191



Testing What Happens When an Immunotherapy Drug (Pembrolizumab) is Added to Radiation or 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 in combination with radiation therapy or pembrolizumab alone compared to the usual approach (chemotherapy 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. Chemotherapy drugs, such as cisplatin and carboplatin kill tumor cells by stopping them from dividing. 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 in combination with radiation therapy or 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., computed tomography [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) 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
Status: ACTIVE
Contact: Site Public Contact
Email: tmyrick@uab.edu

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

Sutter Roseville Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: hempell@sutterhealth.org

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

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

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

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

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

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

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

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

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

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

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

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

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

Emory University Hospital / Winship Cancer Institute
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Emory University Hospital Midtown
Status: ACTIVE
Contact: Site Public Contact

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

IA
Des Moines
Broadlawns Medical Center
Status: ACTIVE
Contact: Site Public Contact

Iowa Lutheran Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Iowa Methodist Medical Center
Status: ACTIVE
Contact: Site Public Contact

Medical Oncology and Hematology Associates-Des Moines
Status: ACTIVE
Contact: Site Public Contact

West Des Moines
Methodist West Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

IL
Danville
Carle on Vermilion
Status: ACTIVE
Contact: Site Public Contact
Email: Research@carle.com

Decatur
Cancer Care Specialists of Illinois - Decatur
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Decatur Memorial Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Effingham
Carle Physician Group-Effingham
Status: ACTIVE
Contact: Site Public Contact
Email: Research@carle.com

Crossroads Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Mattoon
Carle Physician Group-Mattoon / Charleston
Status: ACTIVE
Contact: Site Public Contact
Email: Research@carle.com

Maywood
Loyola University Medical Center
Status: ACTIVE
Contact: Site Public Contact

Springfield
Memorial Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: pallante.beth@mhsil.com

Southern Illinois University School of Medicine
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Springfield Clinic
Status: ACTIVE
Contact: Site Public Contact

Urbana
Carle Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: Research@carle.com

The Carle Foundation Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: Research@carle.com

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

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

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

University of Kansas Hospital-Indian Creek Campus
Status: ACTIVE
Contact: Site Public Contact
Email: KUCC_Navigation@kumc.edu

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

KY
Lexington
University of Kentucky / Markey Cancer Center
Status: ACTIVE
Contact: Site Public Contact

MA
Boston
Tufts Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: ContactUsCancerCenter@TuftsMedicalCenter.org

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

University of Maryland / Greenebaum Cancer Center
Status: ACTIVE
Contact: Site Public Contact

Columbia
Central Maryland Radiation Oncology in Howard County
Status: ACTIVE
Contact: Site Public Contact

Glen Burnie
UM Baltimore Washington Medical Center / Tate Cancer Center
Status: ACTIVE
Contact: Site Public Contact

MI
Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: ACTIVE
Contact: Site Public Contact

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

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

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

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

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

Kansas City
University of Kansas Cancer Center - North
Status: ACTIVE
Contact: Site Public Contact
Email: KUCC_Navigation@kumc.edu

Lee's Summit
University of Kansas Cancer Center - Lee's Summit
Status: ACTIVE
Contact: Site Public Contact
Email: KUCC_Navigation@kumc.edu

North Kansas City
University of Kansas Cancer Center at North Kansas City Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: KUCC_Navigation@kumc.edu

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

Siteman Cancer Center-South County
Status: ACTIVE
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Washington University School of Medicine
Status: ACTIVE
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Saint Peters
Siteman Cancer Center at Saint Peters Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Springfield
Mercy Hospital Springfield
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

MS
Jackson
University of Mississippi Medical Center
Status: ACTIVE
Contact: Site Public Contact

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

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

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

NE
Omaha
Nebraska Methodist Hospital
Status: ACTIVE
Contact: Site Public Contact

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

Mount Sinai Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: CCTO@mssm.edu

Mount Sinai Union Square
Status: ACTIVE
Contact: Site Public Contact
Email: CCTO@mssm.edu

Stony Brook
Stony Brook University Medical Center
Status: ACTIVE
Contact: Site Public Contact

OH
Centerville
Dayton Physicians LLC-Miami Valley South
Status: ACTIVE
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Miami Valley Hospital South
Status: ACTIVE
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Cleveland
Cleveland Clinic Foundation
Status: ACTIVE
Contact: Site Public Contact
Email: TaussigResearch@ccf.org

Dayton
Dayton Physician LLC-Miami Valley Hospital North
Status: ACTIVE
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Miami Valley Hospital North
Status: ACTIVE
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Kettering
Greater Dayton Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Kettering Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

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

Oklahoma City
University of Oklahoma Health Sciences Center
Status: ACTIVE
Contact: Site Public Contact
Email: ou-clinical-trials@ouhsc.edu

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

Providence Cancer Institute Clackamas Clinic
Status: ACTIVE
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

Newberg
Providence Newberg Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

Portland
Providence Portland Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

Providence Saint Vincent Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

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

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

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

Philadelphia
Fox Chase Cancer Center
Status: ACTIVE
Contact: Site Public Contact

Temple University Hospital
Status: ACTIVE
Contact: Site Public Contact

Thomas Jefferson University Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: ONCTrialNow@jefferson.edu

Pittsburgh
UPMC-Shadyside Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact

University of Pittsburgh Cancer Institute (UPCI)
Status: ACTIVE
Contact: Site Public Contact

Wilkes-Barre
Geisinger Wyoming Valley / Henry Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: HemonCCTrials@geisinger.edu

York
UPMC Memorial
Status: ACTIVE
Contact: Site Public Contact

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

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

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

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

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

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

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

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

Menomonee Falls
Froedtert Menomonee Falls Hospital
Status: ACTIVE
Contact: Site Public Contact

Milwaukee
Medical College of Wisconsin
Status: ACTIVE
Contact: Site Public Contact

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

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

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

SECONDARY OBJECTIVES:
I. To evaluate the following endpoints in all 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 groups compared to control.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM A: Patients receive pembrolizumab intravenously (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 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 B: Patients receive cisplatin or carboplatin IV on day 1. Treatment repeats every 7 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo IMRT or PBRT 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.

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.


EA3191 Home Page
ECOG-ACRIN Cancer Research Group