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
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CA
Roseville
Sutter Cancer Centers Radiation Oncology Services-Roseville
Contact: Site Public Contact
Email: NCIclinicaltrials@sutterhealth.org
Sutter Roseville Medical Center
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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
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Email: canceranswers@yale.edu
Waterford
Smilow Cancer Hospital Care Center - Waterford
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Email: canceranswers@yale.edu
DC
Washington
MedStar Washington Hospital Center
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FL
Coral Gables
UM Sylvester Comprehensive Cancer Center at Coral Gables
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Deerfield Beach
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
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Gainesville
University of Florida Health Science Center - Gainesville
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Email: cancer-center@ufl.edu
Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
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Plantation
UM Sylvester Comprehensive Cancer Center at Plantation
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Tampa
Moffitt Cancer Center
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Email: ClinicalTrials@moffitt.org
Moffitt Cancer Center - McKinley Campus
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Email: ClinicalTrials@moffitt.org
Moffitt Cancer Center-International Plaza
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Email: ClinicalTrials@moffitt.org
GA
Atlanta
Emory Proton Therapy Center
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Email: allyson.anderson@emory.edu
Emory University Hospital Midtown
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Emory University Hospital/Winship Cancer Institute
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Savannah
Memorial Health University Medical Center
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Email: Lorraine.OHara@hcahealthcare.com
IA
Ankeny
Mission Cancer and Blood - Ankeny
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Council Bluffs
Heartland Oncology and Hematology LLP
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Methodist Jennie Edmundson Hospital
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Email: kathryn.bartz@nmhs.org
Des Moines
Broadlawns Medical Center
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Iowa Lutheran Hospital
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Iowa Methodist Medical Center
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Mission Cancer and Blood - 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
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Northwestern University
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Email: cancer@northwestern.edu
University of Illinois
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Danville
Carle at The Riverfront
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Email: Research@Carle.com
DeKalb
Northwestern Medicine Cancer Center Kishwaukee
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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
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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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O'Fallon
HSHS Saint Elizabeth's Hospital
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Email: morganthaler.jodi@mhsil.com
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
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Email: Donald.Smith3@nm.org
IN
Richmond
Reid Health
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Email: clinical.trials@daytonncorp.org
KS
Kansas City
University of Kansas Cancer Center
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Email: KUCC_Navigation@kumc.edu
Overland Park
University of Kansas Cancer Center-Overland Park
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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
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Email: KUCC_Navigation@kumc.edu
KY
Lexington
University of Kentucky/Markey Cancer Center
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Louisville
The James Graham Brown Cancer Center at University of Louisville
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UofL Health Medical Center Northeast
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Email: ctoinfo@louisville.edu
MA
Boston
Tufts Medical Center
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Email: ContactUsCancerCenter@TuftsMedicalCenter.org
MD
Baltimore
Maryland Proton Treatment Center
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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
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Detroit
Wayne State University/Karmanos Cancer Institute
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Email: ctoadmin@karmanos.org
Farmington Hills
Weisberg Cancer Treatment Center
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Email: ctoadmin@karmanos.org
MN
Bemidji
Sanford Joe Lueken Cancer Center
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Email: OncologyClinicalTrialsFargo@sanfordhealth.org
MO
Cape Girardeau
Saint Francis Medical Center
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Email: sfmc@sfmc.net
Creve Coeur
Siteman Cancer Center at West County Hospital
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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
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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 Sletten Cancer Institute
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Email: mccinfo@mtcancer.org
Kalispell
Kalispell Regional Medical Center
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Email: mccinfo@mtcancer.org
Missoula
Community Medical Center
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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
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Email: stacey.phelps@conehealth.com
ND
Bismarck
Sanford Bismarck Medical Center
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Email: OncologyClinicalTrialsFargo@sanfordhealth.org
Fargo
Sanford Roger Maris Cancer Center
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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
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Email: info@oa-oc.com
NM
Albuquerque
University of New Mexico Cancer Center
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Email: HSC-ClinicalTrialInfo@salud.unm.edu
NY
New York
Mount Sinai Chelsea
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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
Beavercreek
Indu and Raj Soin Medical Center
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Email: clinical.trials@daytonncorp.org
Centerville
Dayton Physicians LLC-Miami Valley South
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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 Physician LLC - Englewood
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Email: clinical.trials@daytonncorp.org
Miami Valley Hospital North
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Email: clinical.trials@daytonncorp.org
Premier Blood and Cancer Center
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Franklin
Atrium Medical Center-Middletown Regional Hospital
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Email: clinical.trials@daytonncorp.org
Dayton Physicians LLC-Atrium
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Email: clinical.trials@daytonncorp.org
Greenville
Miami Valley Cancer Care and Infusion
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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
Troy
Upper Valley Medical Center
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Email: clinical.trials@daytonncorp.org
OK
Lawton
Cancer Centers of Southwest Oklahoma Research
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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
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Email: ecog.rss@jimmy.harvard.edu
Danville
Geisinger Medical Center
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Email: HemonCCTrials@geisinger.edu
Lewisburg
Geisinger Medical Oncology-Lewisburg
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Email: HemonCCTrials@geisinger.edu
Philadelphia
Fox Chase Cancer Center
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Jefferson Torresdale Hospital
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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
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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
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Email: ewd_research_admin@hshs.org
Menomonee Falls
Froedtert Menomonee Falls Hospital
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Milwaukee
Medical College of Wisconsin
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Oak Creek
Drexel Town Square Health Center
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Sturgeon Bay
Saint Vincent Hospital Cancer Center at Sturgeon Bay
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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.