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
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
- Recurrent Head and Neck Squamous Cell Carcinoma
- Recurrent Hypopharyngeal Squamous Cell Carcinoma
- Recurrent Laryngeal Squamous Cell Carcinoma
- Recurrent Oral Cavity Squamous Cell Carcinoma
- Recurrent Oropharyngeal Squamous Cell Carcinoma
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
| Arm | Description | Assigned 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. |
|
|
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. |
|
|
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. |
|
Recruiting Locations
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama 35233
Birmingham, Alabama 35233
Sutter Cancer Centers Radiation Oncology Services-Roseville
Roseville, California 95661
Roseville, California 95661
Sutter Roseville Medical Center
Roseville, California 95661
Roseville, California 95661
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut 06510
New Haven, Connecticut 06510
Yale University
New Haven, Connecticut 06520
New Haven, Connecticut 06520
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida 33146
Coral Gables, Florida 33146
Contact:
Site Public Contact
305-243-2647
Site Public Contact
305-243-2647
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida 33442
Deerfield Beach, Florida 33442
Contact:
Site Public Contact
305-243-2647
Site Public Contact
305-243-2647
University of Florida Health Science Center - Gainesville
Gainesville, Florida 32610
Gainesville, Florida 32610
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida 33136
Miami, Florida 33136
Contact:
Site Public Contact
305-243-2647
Site Public Contact
305-243-2647
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida 33324
Plantation, Florida 33324
Contact:
Site Public Contact
305-243-2647
Site Public Contact
305-243-2647
Moffitt Cancer Center - McKinley Campus
Tampa, Florida 33612
Tampa, Florida 33612
Moffitt Cancer Center
Tampa, Florida 33612
Tampa, Florida 33612
Emory Proton Therapy Center
Atlanta, Georgia 30308
Atlanta, Georgia 30308
Emory University Hospital Midtown
Atlanta, Georgia 30308
Atlanta, Georgia 30308
Contact:
Site Public Contact
888-946-7447
Site Public Contact
888-946-7447
Memorial Health University Medical Center
Savannah, Georgia 31404
Savannah, Georgia 31404
Carle on Vermilion
Danville, Illinois 61832
Danville, Illinois 61832
Decatur Memorial Hospital
Decatur, Illinois 62526
Decatur, Illinois 62526
Carle Physician Group-Effingham
Effingham, Illinois 62401
Effingham, Illinois 62401
Crossroads Cancer Center
Effingham, Illinois 62401
Effingham, Illinois 62401
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois 61938
Mattoon, Illinois 61938
Loyola University Medical Center
Maywood, Illinois 60153
Maywood, Illinois 60153
Contact:
Site Public Contact
708-226-4357
Site Public Contact
708-226-4357
Springfield Clinic
Springfield, Illinois 62702
Springfield, Illinois 62702
Contact:
Site Public Contact
800-444-7541
Site Public Contact
800-444-7541
Memorial Medical Center
Springfield, Illinois 62781
Springfield, Illinois 62781
Carle Cancer Center
Urbana, Illinois 61801
Urbana, Illinois 61801
Reid Health
Richmond, Indiana 47374
Richmond, Indiana 47374
Iowa Methodist Medical Center
Des Moines, Iowa 50309
Des Moines, Iowa 50309
Contact:
Site Public Contact
515-241-6727
Site Public Contact
515-241-6727
Medical Oncology and Hematology Associates-Des Moines
Des Moines, Iowa 50309
Des Moines, Iowa 50309
Contact:
Site Public Contact
515-282-2921
Site Public Contact
515-282-2921
Broadlawns Medical Center
Des Moines, Iowa 50314
Des Moines, Iowa 50314
Contact:
Site Public Contact
515-282-2200
Site Public Contact
515-282-2200
University of Kansas Cancer Center
Kansas City, Kansas 66160
Kansas City, Kansas 66160
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas 66210
Overland Park, Kansas 66210
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas 66211
Overland Park, Kansas 66211
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas 66205
Westwood, Kansas 66205
University of Kentucky/Markey Cancer Center
Lexington, Kentucky 40536
Lexington, Kentucky 40536
Contact:
Site Public Contact
859-257-3379
Site Public Contact
859-257-3379
Maryland Proton Treatment Center
Baltimore, Maryland 21201
Baltimore, Maryland 21201
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland 21201
Baltimore, Maryland 21201
Contact:
Site Public Contact
800-888-8823
Site Public Contact
800-888-8823
Central Maryland Radiation Oncology in Howard County
Columbia, Maryland 21044
Columbia, Maryland 21044
Contact:
Site Public Contact
443-546-1300
Site Public Contact
443-546-1300
UM Baltimore Washington Medical Center/Tate Cancer Center
Glen Burnie, Maryland 21061
Glen Burnie, Maryland 21061
Contact:
Site Public Contact
410-553-8100
Site Public Contact
410-553-8100
Tufts Medical Center
Boston, Massachusetts 02111
Boston, Massachusetts 02111
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan 48109
Ann Arbor, Michigan 48109
Contact:
Site Public Contact
800-865-1125
Site Public Contact
800-865-1125
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan 48201
Detroit, Michigan 48201
Weisberg Cancer Treatment Center
Farmington Hills, Michigan 48334
Farmington Hills, Michigan 48334
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota 56601
Bemidji, Minnesota 56601
University of Mississippi Medical Center
Jackson, Mississippi 39216
Jackson, Mississippi 39216
Contact:
Site Public Contact
601-815-6700
Site Public Contact
601-815-6700
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri 63141
Creve Coeur, Missouri 63141
University of Kansas Cancer Center - North
Kansas City, Missouri 64154
Kansas City, Missouri 64154
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri 64064
Lee's Summit, Missouri 64064
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri 64116
North Kansas City, Missouri 64116
Washington University School of Medicine
Saint Louis, Missouri 63110
Saint Louis, Missouri 63110
Siteman Cancer Center-South County
Saint Louis, Missouri 63129
Saint Louis, Missouri 63129
Siteman Cancer Center at Christian Hospital
Saint Louis, Missouri 63136
Saint Louis, Missouri 63136
Siteman Cancer Center at Saint Peters Hospital
Saint Peters, Missouri 63376
Saint Peters, Missouri 63376
Kalispell Regional Medical Center
Kalispell, Montana 59901
Kalispell, Montana 59901
Nebraska Methodist Hospital
Omaha, Nebraska 68114
Omaha, Nebraska 68114
Contact:
Site Public Contact
402-354-5144
Site Public Contact
402-354-5144
Mount Sinai Union Square
New York, New York 10003
New York, New York 10003
Mount Sinai Chelsea
New York, New York 10011
New York, New York 10011
Mount Sinai Hospital
New York, New York 10029
New York, New York 10029
Stony Brook University Medical Center
Stony Brook, New York 11794
Stony Brook, New York 11794
Contact:
Site Public Contact
800-862-2215
Site Public Contact
800-862-2215
Sanford Bismarck Medical Center
Bismarck, North Dakota 58501
Bismarck, North Dakota 58501
Sanford Roger Maris Cancer Center
Fargo, North Dakota 58122
Fargo, North Dakota 58122
Dayton Physicians LLC-Miami Valley South
Centerville, Ohio 45459
Centerville, Ohio 45459
Miami Valley Hospital South
Centerville, Ohio 45459
Centerville, Ohio 45459
Cleveland Clinic Foundation
Cleveland, Ohio 44195
Cleveland, Ohio 44195
Dayton Physician LLC-Miami Valley Hospital North
Dayton, Ohio 45415
Dayton, Ohio 45415
Miami Valley Hospital North
Dayton, Ohio 45415
Dayton, Ohio 45415
Greater Dayton Cancer Center
Kettering, Ohio 45409
Kettering, Ohio 45409
Kettering Medical Center
Kettering, Ohio 45429
Kettering, Ohio 45429
Cancer Centers of Southwest Oklahoma Research
Lawton, Oklahoma 73505
Lawton, Oklahoma 73505
Contact:
Site Public Contact
877-231-4440
Site Public Contact
877-231-4440
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
Oklahoma City, Oklahoma 73104
Providence Cancer Institute Clackamas Clinic
Clackamas, Oregon 97015
Clackamas, Oregon 97015
Providence Newberg Medical Center
Newberg, Oregon 97132
Newberg, Oregon 97132
Providence Portland Medical Center
Portland, Oregon 97213
Portland, Oregon 97213
Providence Saint Vincent Medical Center
Portland, Oregon 97225
Portland, Oregon 97225
Geisinger Medical Center
Danville, Pennsylvania 17822
Danville, Pennsylvania 17822
Geisinger Medical Oncology-Lewisburg
Lewisburg, Pennsylvania 17837
Lewisburg, Pennsylvania 17837
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania 19107
Philadelphia, Pennsylvania 19107
Fox Chase Cancer Center
Philadelphia, Pennsylvania 19111
Philadelphia, Pennsylvania 19111
Contact:
Site Public Contact
215-728-4790
Site Public Contact
215-728-4790
Temple University Hospital
Philadelphia, Pennsylvania 19140
Philadelphia, Pennsylvania 19140
Contact:
Site Public Contact
215-728-2983
Site Public Contact
215-728-2983
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania 15232
Pittsburgh, Pennsylvania 15232
Contact:
Site Public Contact
412-647-8073
Site Public Contact
412-647-8073
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania 18711
Wilkes-Barre, Pennsylvania 18711
UPMC Memorial
York, Pennsylvania 17408
York, Pennsylvania 17408
Contact:
Site Public Contact
717-724-6760
Site Public Contact
717-724-6760
Medical University of South Carolina
Charleston, South Carolina 29425
Charleston, South Carolina 29425
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota 57117-5134
Sioux Falls, South Dakota 57117-5134
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah 84112
Salt Lake City, Utah 84112
VCU Massey Cancer Center at Stony Point
Richmond, Virginia 23235
Richmond, Virginia 23235
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia 23298
Richmond, Virginia 23298
HSHS Sacred Heart Hospital
Eau Claire, Wisconsin 54701
Eau Claire, Wisconsin 54701
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin 54301
Green Bay, Wisconsin 54301
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin 54303
Green Bay, Wisconsin 54303
Froedtert Menomonee Falls Hospital
Menomonee Falls, Wisconsin 53051
Menomonee Falls, Wisconsin 53051
Contact:
Site Public Contact
262-257-5100
Site Public Contact
262-257-5100
Medical College of Wisconsin
Milwaukee, Wisconsin 53226
Milwaukee, Wisconsin 53226
Contact:
Site Public Contact
414-805-3666
Site Public Contact
414-805-3666
Drexel Town Square Health Center
Oak Creek, Wisconsin 53154
Oak Creek, Wisconsin 53154
Contact:
Site Public Contact
414-805-0505
Site Public Contact
414-805-0505
Saint Vincent Hospital Cancer Center at Sturgeon Bay
Sturgeon Bay, Wisconsin 54235-1495
Sturgeon Bay, Wisconsin 54235-1495
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