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
Birmingham, Alabama 35233
Little Rock, Arkansas 72205
Site Public Contact
501-686-8274
New Haven, Connecticut 06510
New Haven, Connecticut 06520
Washington, District of Columbia 20010
Site Public Contact
202-877-8839
Coral Gables, Florida 33146
Site Public Contact
305-243-2647
Deerfield Beach, Florida 33442
Site Public Contact
305-243-2647
Gainesville, Florida 32610
Miami, Florida 33136
Site Public Contact
305-243-2647
Plantation, Florida 33324
Site Public Contact
305-243-2647
Tampa, Florida 33612
Tampa, Florida 33612
Atlanta, Georgia 30308
Atlanta, Georgia 30308
Site Public Contact
888-946-7447
Savannah, Georgia 31404
Chicago, Illinois 60611
Danville, Illinois 61832
Decatur, Illinois 62526
DeKalb, Illinois 60115
Effingham, Illinois 62401
Effingham, Illinois 62401
Geneva, Illinois 60134
Mattoon, Illinois 61938
Maywood, Illinois 60153
Site Public Contact
708-226-4357
Springfield, Illinois 62702
Site Public Contact
800-444-7541
Springfield, Illinois 62781
Urbana, Illinois 61801
Warrenville, Illinois 60555
Richmond, Indiana 47374
Des Moines, Iowa 50309
Site Public Contact
515-241-6727
Des Moines, Iowa 50309
Site Public Contact
515-241-3305
Des Moines, Iowa 50314
Site Public Contact
515-282-2200
Kansas City, Kansas 66160
Overland Park, Kansas 66210
Overland Park, Kansas 66211
Westwood, Kansas 66205
Lexington, Kentucky 40536
Site Public Contact
859-257-3379
Baltimore, Maryland 21201
Baltimore, Maryland 21201
Site Public Contact
800-888-8823
Columbia, Maryland 21044
Site Public Contact
443-546-1300
Glen Burnie, Maryland 21061
Site Public Contact
410-553-8100
Boston, Massachusetts 02111
Ann Arbor, Michigan 48109
Site Public Contact
800-865-1125
Bemidji, Minnesota 56601
Jackson, Mississippi 39216
Site Public Contact
601-815-6700
Kansas City, Missouri 64154
Lee's Summit, Missouri 64064
North Kansas City, Missouri 64116
Great Falls, Montana 59405
Kalispell, Montana 59901
Omaha, Nebraska 68114
Site Public Contact
402-354-5144
New York, New York 10003
New York, New York 10011
New York, New York 10029
Stony Brook, New York 11794
Site Public Contact
800-862-2215
Asheboro, North Carolina 27203
Greensboro, North Carolina 27403
Reidsville, North Carolina 27320
Bismarck, North Dakota 58501
Fargo, North Dakota 58122
Centerville, Ohio 45459
Centerville, Ohio 45459
Cleveland, Ohio 44195
Dayton, Ohio 45415
Dayton, Ohio 45415
Kettering, Ohio 45409
Kettering, Ohio 45429
Lawton, Oklahoma 73505
Site Public Contact
877-231-4440
Oklahoma City, Oklahoma 73104
Clackamas, Oregon 97015
Newberg, Oregon 97132
Portland, Oregon 97213
Portland, Oregon 97225
Lewisburg, Pennsylvania 17837
Philadelphia, Pennsylvania 19107
Pittsburgh, Pennsylvania 15232
Site Public Contact
412-647-8073
Wilkes-Barre, Pennsylvania 18711
York, Pennsylvania 17408
Site Public Contact
717-724-6760
Charleston, South Carolina 29425
Sioux Falls, South Dakota 57117-5134
Nashville, Tennessee 37232
Site Public Contact
800-811-8480
Richmond, Virginia 23235
Richmond, Virginia 23298
Eau Claire, Wisconsin 54701
Green Bay, Wisconsin 54301
Green Bay, Wisconsin 54303
Menomonee Falls, Wisconsin 53051
Site Public Contact
262-257-5100
Milwaukee, Wisconsin 53226
Site Public Contact
414-805-3666
Oak Creek, Wisconsin 53154
Site Public Contact
414-805-0505
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