Purpose

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.

Conditions

Eligibility

Eligible Ages
Between 18 Years and 79 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 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 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) - 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 - 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

Exclusion Criteria

  • 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 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 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) - 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 - 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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A (pembrolizumab, IMRT, PBRT)
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 also undergo IMRT or PBRT QD for a total of 30 fractions in the absence of disease progression or unacceptable toxicity.
  • Radiation: Intensity-Modulated Radiation Therapy
    Undergo IMRT
  • Biological: Pembrolizumab
    Given IV
  • Radiation: Proton Beam Radiation Therapy
    Undergo PBRT
Active Comparator
Arm B (cisplatin, carboplatin, IMRT, PBRT)
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.
  • Drug: Carboplatin
    Given IV
  • Drug: Cisplatin
    Given IV
  • Radiation: Intensity-Modulated Radiation Therapy
    Undergo IMRT
  • Radiation: Proton Beam Radiation Therapy
    Undergo PBRT
Experimental
Arm C (pembrolizumab)
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.
  • Biological: Pembrolizumab
    Given IV

Recruiting Locations

University of Alabama at Birmingham Cancer Center
Birmingham, Alabama 35233
Contact:
Site Public Contact
205-934-0220
tmyrick@uab.edu

Sutter Cancer Centers Radiation Oncology Services-Roseville
Roseville, California 95661
Contact:
Site Public Contact
415-209-2683
hempell@sutterhealth.org

Sutter Roseville Medical Center
Roseville, California 95661
Contact:
Site Public Contact
415-209-2683
hempell@sutterhealth.org

Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut 06510
Contact:
Site Public Contact
203-785-5702
canceranswers@yale.edu

Yale University
New Haven, Connecticut 06520
Contact:
Site Public Contact
203-785-5702
canceranswers@yale.edu

UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida 33146
Contact:
Site Public Contact
305-243-2647

UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida 33442
Contact:
Site Public Contact
305-243-2647

University of Florida Health Science Center - Gainesville
Gainesville, Florida 32610
Contact:
Site Public Contact
352-273-8010
cancer-center@ufl.edu

University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida 33136
Contact:
Site Public Contact
305-243-2647

UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida 33324
Contact:
Site Public Contact
305-243-2647

Moffitt Cancer Center - McKinley Campus
Tampa, Florida 33612
Contact:
Site Public Contact
800-679-0775
ClinicalTrials@moffitt.org

Moffitt Cancer Center
Tampa, Florida 33612
Contact:
Site Public Contact
800-679-0775
ClinicalTrials@moffitt.org

Emory Proton Therapy Center
Atlanta, Georgia 30308
Contact:
Site Public Contact
404-251-2854
allyson.anderson@emory.edu

Emory University Hospital Midtown
Atlanta, Georgia 30308
Contact:
Site Public Contact
888-946-7447

Memorial Health University Medical Center
Savannah, Georgia 31404
Contact:
Site Public Contact
912-350-7887
Lorraine.OHara@hcahealthcare.com

Carle on Vermilion
Danville, Illinois 61832
Contact:
Site Public Contact
800-446-5532
Research@carle.com

Decatur Memorial Hospital
Decatur, Illinois 62526
Contact:
Site Public Contact
217-876-4762
morganthaler.jodi@mhsil.com

Carle Physician Group-Effingham
Effingham, Illinois 62401
Contact:
Site Public Contact
800-446-5532
Research@carle.com

Crossroads Cancer Center
Effingham, Illinois 62401
Contact:
Site Public Contact
217-876-4762
morganthaler.jodi@mhsil.com

Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois 61938
Contact:
Site Public Contact
800-446-5532
Research@carle.com

Loyola University Medical Center
Maywood, Illinois 60153
Contact:
Site Public Contact
708-226-4357

Springfield Clinic
Springfield, Illinois 62702
Contact:
Site Public Contact
800-444-7541

Memorial Medical Center
Springfield, Illinois 62781
Contact:
Site Public Contact
217-528-7541
pallante.beth@mhsil.com

Carle Cancer Center
Urbana, Illinois 61801
Contact:
Site Public Contact
800-446-5532
Research@carle.com

Reid Health
Richmond, Indiana 47374
Contact:
Site Public Contact
937-528-2900
clinical.trials@daytonncorp.org

Iowa Methodist Medical Center
Des Moines, Iowa 50309
Contact:
Site Public Contact
515-241-6727

Medical Oncology and Hematology Associates-Des Moines
Des Moines, Iowa 50309
Contact:
Site Public Contact
515-282-2921

Broadlawns Medical Center
Des Moines, Iowa 50314
Contact:
Site Public Contact
515-282-2200

University of Kansas Cancer Center
Kansas City, Kansas 66160
Contact:
Site Public Contact
913-588-3671
KUCC_Navigation@kumc.edu

University of Kansas Cancer Center-Overland Park
Overland Park, Kansas 66210
Contact:
Site Public Contact
913-588-3671
KUCC_Navigation@kumc.edu

University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas 66211
Contact:
Site Public Contact
913-588-3671
KUCC_Navigation@kumc.edu

University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas 66205
Contact:
Site Public Contact
913-588-3671
KUCC_Navigation@kumc.edu

University of Kentucky/Markey Cancer Center
Lexington, Kentucky 40536
Contact:
Site Public Contact
859-257-3379

Maryland Proton Treatment Center
Baltimore, Maryland 21201
Contact:
Site Public Contact
410-369-5226
info@mdproton.com

University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland 21201
Contact:
Site Public Contact
800-888-8823

Central Maryland Radiation Oncology in Howard County
Columbia, Maryland 21044
Contact:
Site Public Contact
443-546-1300

UM Baltimore Washington Medical Center/Tate Cancer Center
Glen Burnie, Maryland 21061
Contact:
Site Public Contact
410-553-8100

Tufts Medical Center
Boston, Massachusetts 02111
Contact:
Site Public Contact
617-636-5000
ContactUsCancerCenter@TuftsMedicalCenter.org

University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan 48109
Contact:
Site Public Contact
800-865-1125

Wayne State University/Karmanos Cancer Institute
Detroit, Michigan 48201
Contact:
Site Public Contact
313-576-9790
ctoadmin@karmanos.org

Weisberg Cancer Treatment Center
Farmington Hills, Michigan 48334
Contact:
Site Public Contact
313-576-9790
ctoadmin@karmanos.org

Sanford Joe Lueken Cancer Center
Bemidji, Minnesota 56601
Contact:
Site Public Contact
218-333-5000
OncologyClinicalTrialsFargo@sanfordhealth.org

University of Mississippi Medical Center
Jackson, Mississippi 39216
Contact:
Site Public Contact
601-815-6700

Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri 63141
Contact:
Site Public Contact
800-600-3606
info@siteman.wustl.edu

University of Kansas Cancer Center - North
Kansas City, Missouri 64154
Contact:
Site Public Contact
913-588-3671
KUCC_Navigation@kumc.edu

University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri 64064
Contact:
Site Public Contact
913-588-3671
KUCC_Navigation@kumc.edu

University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri 64116
Contact:
Site Public Contact
913-588-3671
KUCC_Navigation@kumc.edu

Washington University School of Medicine
Saint Louis, Missouri 63110
Contact:
Site Public Contact
800-600-3606
info@siteman.wustl.edu

Siteman Cancer Center-South County
Saint Louis, Missouri 63129
Contact:
Site Public Contact
800-600-3606
info@siteman.wustl.edu

Siteman Cancer Center at Christian Hospital
Saint Louis, Missouri 63136
Contact:
Site Public Contact
800-600-3606
info@siteman.wustl.edu

Siteman Cancer Center at Saint Peters Hospital
Saint Peters, Missouri 63376
Contact:
Site Public Contact
800-600-3606
info@siteman.wustl.edu

Kalispell Regional Medical Center
Kalispell, Montana 59901
Contact:
Site Public Contact
406-969-6060
mccinfo@mtcancer.org

Nebraska Methodist Hospital
Omaha, Nebraska 68114
Contact:
Site Public Contact
402-354-5144

Mount Sinai Union Square
New York, New York 10003
Contact:
Site Public Contact
212-824-7309
CCTO@mssm.edu

Mount Sinai Chelsea
New York, New York 10011
Contact:
Site Public Contact
212-824-7309
CCTO@mssm.edu

Mount Sinai Hospital
New York, New York 10029
Contact:
Site Public Contact
212-824-7309
CCTO@mssm.edu

Stony Brook University Medical Center
Stony Brook, New York 11794
Contact:
Site Public Contact
800-862-2215

Sanford Bismarck Medical Center
Bismarck, North Dakota 58501
Contact:
Site Public Contact
701-323-5760
OncologyClinicalTrialsFargo@sanfordhealth.org

Sanford Roger Maris Cancer Center
Fargo, North Dakota 58122
Contact:
Site Public Contact
701-234-6161
OncologyClinicalTrialsFargo@sanfordhealth.org

Dayton Physicians LLC-Miami Valley South
Centerville, Ohio 45459
Contact:
Site Public Contact
937-528-2900
clinical.trials@daytonncorp.org

Miami Valley Hospital South
Centerville, Ohio 45459
Contact:
Site Public Contact
937-528-2900
clinical.trials@daytonncorp.org

Cleveland Clinic Foundation
Cleveland, Ohio 44195
Contact:
Site Public Contact
866-223-8100
TaussigResearch@ccf.org

Dayton Physician LLC-Miami Valley Hospital North
Dayton, Ohio 45415
Contact:
Site Public Contact
937-528-2900
clinical.trials@daytonncorp.org

Miami Valley Hospital North
Dayton, Ohio 45415
Contact:
Site Public Contact
937-528-2900
clinical.trials@daytonncorp.org

Greater Dayton Cancer Center
Kettering, Ohio 45409
Contact:
Site Public Contact
937-528-2900
clinical.trials@daytonncorp.org

Kettering Medical Center
Kettering, Ohio 45429
Contact:
Site Public Contact
937-528-2900
clinical.trials@daytonncorp.org

Cancer Centers of Southwest Oklahoma Research
Lawton, Oklahoma 73505
Contact:
Site Public Contact
877-231-4440

University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
Contact:
Site Public Contact
405-271-8777
ou-clinical-trials@ouhsc.edu

Providence Cancer Institute Clackamas Clinic
Clackamas, Oregon 97015
Contact:
Site Public Contact
503-215-2614
CanRsrchStudies@providence.org

Providence Newberg Medical Center
Newberg, Oregon 97132
Contact:
Site Public Contact
503-215-2614
CanRsrchStudies@providence.org

Providence Portland Medical Center
Portland, Oregon 97213
Contact:
Site Public Contact
503-215-2614
CanRsrchStudies@providence.org

Providence Saint Vincent Medical Center
Portland, Oregon 97225
Contact:
Site Public Contact
503-215-2614
CanRsrchStudies@providence.org

UPMC Altoona
Altoona, Pennsylvania 16601
Contact:
Site Public Contact
ecog.rss@jimmy.harvard.edu

Geisinger Medical Center
Danville, Pennsylvania 17822
Contact:
Site Public Contact
570-271-5251
HemonCCTrials@geisinger.edu

Geisinger Medical Oncology-Lewisburg
Lewisburg, Pennsylvania 17837
Contact:
Site Public Contact
570-374-8555
HemonCCTrials@geisinger.edu

Thomas Jefferson University Hospital
Philadelphia, Pennsylvania 19107
Contact:
Site Public Contact
215-600-9151
ONCTrialNow@jefferson.edu

Fox Chase Cancer Center
Philadelphia, Pennsylvania 19111
Contact:
Site Public Contact
215-728-4790

Temple University Hospital
Philadelphia, Pennsylvania 19140
Contact:
Site Public Contact
215-728-2983

University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania 15232
Contact:
Site Public Contact
412-647-8073

Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania 18711
Contact:
Site Public Contact
570-271-5251
HemonCCTrials@geisinger.edu

UPMC Memorial
York, Pennsylvania 17408
Contact:
Site Public Contact
717-724-6760

Medical University of South Carolina
Charleston, South Carolina 29425
Contact:
Site Public Contact
843-792-9321
hcc-clinical-trials@musc.edu

Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota 57117-5134
Contact:
Site Public Contact
605-312-3320
OncologyClinicalTrialsSF@SanfordHealth.org

Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah 84112
Contact:
Site Public Contact
888-424-2100
cancerinfo@hci.utah.edu

VCU Massey Cancer Center at Stony Point
Richmond, Virginia 23235
Contact:
Site Public Contact
ctoclinops@vcu.edu

Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia 23298
Contact:
Site Public Contact
CTOclinops@vcu.edu

HSHS Sacred Heart Hospital
Eau Claire, Wisconsin 54701
Contact:
Site Public Contact
920-433-8889
ewd_research_admin@hshs.org

Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin 54301
Contact:
Site Public Contact
920-433-8889
ewd_research_admin@hshs.org

Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin 54303
Contact:
Site Public Contact
920-433-8889
ewd_research_admin@hshs.org

Froedtert Menomonee Falls Hospital
Menomonee Falls, Wisconsin 53051
Contact:
Site Public Contact
262-257-5100

Medical College of Wisconsin
Milwaukee, Wisconsin 53226
Contact:
Site Public Contact
414-805-3666

Drexel Town Square Health Center
Oak Creek, Wisconsin 53154
Contact:
Site Public Contact
414-805-0505

Saint Vincent Hospital Cancer Center at Sturgeon Bay
Sturgeon Bay, Wisconsin 54235-1495
Contact:
Site Public Contact
920-433-8889
ewd_research_admin@hshs.org

More Details

NCT ID
NCT04671667
Status
Recruiting
Sponsor
National Cancer Institute (NCI)

Detailed Description

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.