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, Arkansas 72205
Site Public Contact
501-686-8274
Anaheim, California 92806
Bellflower, California 90706
Irvine, California 92612
La Jolla, California 92093
Los Angeles, California 90027
Ontario, California 91761
Orange, California 92868
San Diego, California 92121
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858-299-5982
New Haven, Connecticut 06510
New Haven, Connecticut 06520
Trumbull, Connecticut 06611
Waterford, Connecticut 06385
Washington, District of Columbia 20010
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202-877-8839
Coral Gables, Florida 33146
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305-243-2647
Deerfield Beach, Florida 33442
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Tampa, Florida 33612
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Atlanta, Georgia 30308
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Chicago, Illinois 60612
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DeKalb, Illinois 60115
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Effingham, Illinois 62401
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Maywood, Illinois 60153
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708-226-4357
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Albuquerque, New Mexico 87106
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Bronx, New York 10467
New York, New York 10011
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800-862-2215
Greensboro, North Carolina 27403
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Cleveland, Ohio 44195
Dayton, Ohio 45409
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Dayton, Ohio 45415
Dayton, Ohio 45415
Franklin, Ohio 45005-1066
Franklin, Ohio 45005
Greenville, Ohio 45331
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Kettering, Ohio 45409
Kettering, Ohio 45429
Troy, Ohio 45373
Lawton, Oklahoma 73505
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Oklahoma City, Oklahoma 73104
Newberg, Oregon 97132
Portland, Oregon 97213
Portland, Oregon 97225
Danville, Pennsylvania 17822
Farrell, Pennsylvania 16121
Lewisburg, Pennsylvania 17837
New Castle, Pennsylvania 16105
Philadelphia, Pennsylvania 19107
Philadelphia, Pennsylvania 19111
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215-728-4790
Philadelphia, Pennsylvania 19114
Pittsburgh, Pennsylvania 15215
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Pittsburgh, Pennsylvania 15232
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Pittsburgh, Pennsylvania 15237
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Wilkes-Barre, Pennsylvania 18711
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Charleston, South Carolina 29425
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Yankton, South Dakota 57078
Nashville, Tennessee 37232
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Richmond, Virginia 23235
Richmond, Virginia 23298
Appleton, Wisconsin 54911
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Green Bay, Wisconsin 54303
Menomonee Falls, Wisconsin 53051
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262-257-5100
Milwaukee, Wisconsin 53226
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414-805-3666
Oak Creek, Wisconsin 53154
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414-805-0505
Sturgeon Bay, Wisconsin 54235-1495
West Bend, Wisconsin 53095
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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.