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
Purpose
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.
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 Sex
- All
- Accepts Healthy Volunteers
- No
Criteria
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 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 someone, regardless of 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
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 |
---|---|---|
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. Patients also undergo CT or MRI throughout the trial. |
|
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. Patients also undergo CT or MRI throughout the trial. |
|
Recruiting Locations
Little Rock 4119403, Arkansas 4099753 72205
Site Public Contact
501-686-8274
Anaheim 5323810, California 5332921 92806
Bellflower 5327422, California 5332921 90706
Irvine 5359777, California 5332921 92612
La Jolla 5363943, California 5332921 92093
Los Angeles 5368361, California 5332921 90027
Ontario 5379439, California 5332921 91761
Orange 5379513, California 5332921 92868
San Diego 5391811, California 5332921 92121
Site Public Contact
858-299-5982
New Haven 4839366, Connecticut 4831725 06510
New Haven 4839366, Connecticut 4831725 06520
Trumbull 4844459, Connecticut 4831725 06611
Waterford 8480031, Connecticut 4831725 06385
Coral Gables 4151871, Florida 4155751 33146
Site Public Contact
305-243-2647
Deerfield Beach 4153071, Florida 4155751 33442
Site Public Contact
305-243-2647
Miami 4164138, Florida 4155751 33136
Site Public Contact
305-243-2647
Plantation 4168782, Florida 4155751 33324
Site Public Contact
305-243-2647
Tampa 4174757, Florida 4155751 33612
Tampa 4174757, Florida 4155751 33612
Atlanta 4180439, Georgia 4197000 30308
Atlanta 4180439, Georgia 4197000 30308
Site Public Contact
888-946-7447
Chicago 4887398, Illinois 4896861 60611
Chicago 4887398, Illinois 4896861 60612
Site Public Contact
312-864-5204
Chicago 4887398, Illinois 4896861 60612
Site Public Contact
312-355-3046
Danville 4889426, Illinois 4896861 61832
Decatur 4236895, Illinois 4896861 62526
DeKalb 4889553, Illinois 4896861 60115
Effingham 4237727, Illinois 4896861 62401
Effingham 4237727, Illinois 4896861 62401
Geneva 4893591, Illinois 4896861 60134
Mattoon 4244099, Illinois 4896861 61938
Maywood 4901514, Illinois 4896861 60153
Site Public Contact
708-226-4357
O'Fallon 4245926, Illinois 4896861 62269
Springfield 4250542, Illinois 4896861 62702
Site Public Contact
217-545-7929
Springfield 4250542, Illinois 4896861 62702
Site Public Contact
800-444-7541
Springfield 4250542, Illinois 4896861 62781
Urbana 4914570, Illinois 4896861 61801
Warrenville 4915525, Illinois 4896861 60555
Ankeny 4846960, Iowa 4862182 50023
Site Public Contact
515-241-3305
Council Bluffs 4852832, Iowa 4862182 51503
Site Public Contact
712-322-4136
Council Bluffs 4852832, Iowa 4862182 51503
Des Moines 4853828, Iowa 4862182 50309
Site Public Contact
515-241-6727
Des Moines 4853828, Iowa 4862182 50309
Site Public Contact
515-241-3305
Des Moines 4853828, Iowa 4862182 50314
Site Public Contact
515-282-2200
Waukee 4880981, Iowa 4862182 50263
Site Public Contact
515-241-3305
Lexington 4297983, Kentucky 6254925 40536
Site Public Contact
859-257-3379
Louisville 4299276, Kentucky 6254925 40202
Site Public Contact
502-562-3429
Louisville 4299276, Kentucky 6254925 40245
Baltimore 4347778, Maryland 4361885 21201
Site Public Contact
800-888-8823
Columbia 4352053, Maryland 4361885 21044
Site Public Contact
443-546-1300
Glen Burnie 4356188, Maryland 4361885 21061
Site Public Contact
410-553-8100
Boston 4930956, Massachusetts 6254926 02111
Bemidji 5017822, Minnesota 5037779 56601
Jackson 4431410, Mississippi 4436296 39216
Site Public Contact
601-815-6700
St Louis 4407066, Missouri 4398678 63128
St Louis 4407066, Missouri 4398678 63141
Site Public Contact
314-251-7066
Great Falls 5655240, Montana 5667009 59405
Kalispell 5660340, Montana 5667009 59901
Missoula 5666639, Montana 5667009 59804
Omaha 5074472, Nebraska 5073708 68114
Site Public Contact
402-334-4773
Omaha 5074472, Nebraska 5073708 68114
Site Public Contact
402-354-5144
Albuquerque 5454711, New Mexico 5481136 87106
New York 5128581, New York 5128638 10003
New York 5128581, New York 5128638 10011
New York 5128581, New York 5128638 10029
Rochester 5134086, New York 5128638 14642
Site Public Contact
585-275-5830
Stony Brook 5139865, New York 5128638 11794
Site Public Contact
800-862-2215
The Bronx 5110266, New York 5128638 10461
The Bronx 5110266, New York 5128638 10467
Webster 5143495, New York 5128638 14580
Greensboro 4469146, North Carolina 4482348 27403
Reidsville 4487682, North Carolina 4482348 27320
Bismarck 5688025, North Dakota 5690763 58501
Fargo 5059163, North Dakota 5690763 58122
Centerville 4508204, Ohio 5165418 45459
Cleveland 5150529, Ohio 5165418 44195
Dayton 4509884, Ohio 5165418 45409
Site Public Contact
937-276-8320
Dayton 4509884, Ohio 5165418 45415
Franklin 4512203, Ohio 5165418 45005-1066
Greenville 5156493, Ohio 5165418 45331
Site Public Contact
937-569-7515
Troy 5174358, Ohio 5165418 45373
Lawton 4540737, Oklahoma 4544379 73505
Site Public Contact
877-231-4440
Oklahoma City 4544349, Oklahoma 4544379 73104
Newberg 5742726, Oregon 5744337 97132
Portland 5746545, Oregon 5744337 97213
Portland 5746545, Oregon 5744337 97225
Altoona 5178195, Pennsylvania 6254927 16601
Danville 5186327, Pennsylvania 6254927 17822
Erie 5188843, Pennsylvania 6254927 16505
Farrell 5189377, Pennsylvania 6254927 16121
Lewisburg 5197842, Pennsylvania 6254927 17837
New Castle 5203127, Pennsylvania 6254927 16105
Philadelphia 4560349, Pennsylvania 6254927 19107
Philadelphia 4560349, Pennsylvania 6254927 19111
Site Public Contact
215-728-4790
Philadelphia 4560349, Pennsylvania 6254927 19114
Pittsburgh 5206379, Pennsylvania 6254927 15215
Site Public Contact
412-784-4900
Pittsburgh 5206379, Pennsylvania 6254927 15232
Site Public Contact
412-647-8073
Pittsburgh 5206379, Pennsylvania 6254927 15237
Site Public Contact
412-367-6454
Wilkes-Barre 5219488, Pennsylvania 6254927 18711
York 4562407, Pennsylvania 6254927 17408
Site Public Contact
717-724-6760
Charleston 4574324, South Carolina 4597040 29425
Sioux Falls 5231851, South Dakota 5769223 57105
Sioux Falls 5231851, South Dakota 5769223 57117-5134
Yankton 5233053, South Dakota 5769223 57078
Nashville 4644585, Tennessee 4662168 37232
Site Public Contact
800-811-8480
Richmond 4781708, Virginia 6254928 23235
Richmond 4781708, Virginia 6254928 23298
Appleton 5244080, Wisconsin 5279468 54911
Green Bay 5254962, Wisconsin 5279468 54301
Green Bay 5254962, Wisconsin 5279468 54303
Menomonee Falls 5262630, Wisconsin 5279468 53051
Site Public Contact
262-257-5100
Milwaukee 5263045, Wisconsin 5279468 53226
Site Public Contact
414-805-3666
Oak Creek 5265228, Wisconsin 5279468 53154
Site Public Contact
414-805-0505
Sturgeon Bay 5274867, Wisconsin 5279468 54235-1495
West Bend 5278422, Wisconsin 5279468 53095
Site Public Contact
414-805-0505
More Details
- NCT ID
- NCT04671667
- Status
- Recruiting
- Sponsor
- National Cancer Institute (NCI)
Detailed Description
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.