Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
Purpose
This phase III trial compares the effect of adding cetuximab to pembrolizumab versus pembrolizumab alone in treating patients with head and neck squamous cell carcinoma (HNSCC) that has come back after a period of improvement (recurrent) and/or that has spread from where it first started (primary site) to other places in the body (metastatic). Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of tumor cells. This may help keep tumor cells from growing. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving cetuximab and pembrolizumab together may be more effective at treating patients with recurrent and/or metastatic HNSCC than pembrolizumab alone.
Conditions
- Metastatic Head and Neck Squamous Cell Carcinoma
- Metastatic Hypopharyngeal Squamous Cell Carcinoma
- Metastatic Laryngeal Squamous Cell Carcinoma
- Metastatic Oral Cavity Squamous Cell Carcinoma
- Metastatic Oropharyngeal Squamous Cell Carcinoma
- Recurrent Head and Neck Squamous Cell Carcinoma
- Recurrent Hypopharyngeal Squamous Cell Carcinoma
- Recurrent Laryngeal Squamous Cell Carcinoma
- Recurrent Neck Squamous Cell Carcinoma of Unknown Primary
- Recurrent Oral Cavity Squamous Cell Carcinoma
- Recurrent Oropharyngeal Squamous Cell Carcinoma
- Refractory Head and Neck Squamous Cell Carcinoma
- Refractory Hypopharyngeal Squamous Cell Carcinoma
- Refractory Laryngeal Squamous Cell Carcinoma
- Refractory Oral Cavity Squamous Cell Carcinoma
- Refractory Oropharyngeal Squamous Cell Carcinoma
- Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8
- Stage IV Hypopharyngeal Carcinoma AJCC v8
- Stage IV Laryngeal Cancer AJCC v8
- Stage IV Lip and Oral Cavity Cancer AJCC v8
- Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Criteria
Inclusion Criteria:
- Histologically confirmed diagnosis head and neck squamous cell carcinomas (HNSCC).
- Previously untreated for recurrent and/or metastatic disease incurable by local
therapies.
- Primary tumor location of oral cavity, oropharynx, larynx, or hypopharynx.
- Note: Other primary tumor sites of HNSCC, including nasopharynx primary tumor
are not eligible. Unknown primary tumors may be eligible and can be enrolled at
the discretion of the treatment team with approval by the study chair.
- Measurable disease.
- Must have platinum-refractory disease defined as disease progression during or ≤ 6
months after completion of definitive therapy (chemoradiation therapy) or adjuvant
(post-operative) therapy.
- Patient must have a combined positive score PD-L1 positive (CPS >/= 1) tumor.
- Any radiation therapy must be completed >= 10 days prior to registration.
- Patients should not have received any prior treatment in the recurrent or metastatic
setting.
- Prior therapy with anti PD-1/PD-L1 monoclonal antibody or cetuximab in the curative
setting is allowed if last treatment dose was >= 6 months prior to registration
without evidence of disease progression during that treatment period.
- Patient has not received a live vaccine within 30 days prior to registration.
- Patient does not have a history of any contraindication or has a severe
hypersensitivity to any component of pembrolizumab or cetuximab (≥ grade 3).
- Patient has not received chronic systemic steroid therapy (in dosing exceeding 10 mg
daily of prednisone or equivalent) or any other form of immunosuppressive therapy
within 7 days prior to registration.
- Patient with oropharyngeal cancer only must have negative results from testing of
human papillomavirus (HPV) status defined as p16 immunohistochemistry (IHC) and/or
HPV in situ hybridization (ISH).
- Note: A Clinical Laboratory Improvement Act (CLIA) certified circulating tumor
HPV deoxyribonucleic acid (ctHPVDNA) assay can be used if tissue sample is not
available.
- Age ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Absolute neutrophil count (ANC) ≥ 1,500/mm^3.
- Platelet count ≥ 100,000/mm^3.
- Hemoglobin (Hgb) ≥ 9 g/dL (if < 9 g/dL, then transfusions are acceptable to increase
hemoglobin above 9 g/dL).
- Creatinine ≤ 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine
clearance ≥ 30 mL/min using the Cockcroft-Gault formula for participant with
creatinine levels > 1.5 x institutional ULN.
- Total bilirubin ≤ 1.5 x ULN OR direct bilirubin < ULN for participant with total
bilirubin > 1.5 x institutional ULN.
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT])
≤ 3.0 x ULN unless liver metastases are present in which case < 5.0 x ULN.
- Not pregnant and not nursing, because this study involves an agent that has known
genotoxic, mutagenic, and teratogenic effects.
- Therefore, for women of childbearing potential only, a negative pregnancy test
done ≤ 7 days prior to registration is required.
- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen should be included.
- For treated/stable brain metastases: Patients with treated brain metastases are
eligible if follow-up brain imaging after central nervous system (CNS)-directed
therapy shows no evidence of progression.
- Patients with new or progressive brain metastases (active brain metastases) or
leptomeningeal disease are eligible if the treating physician determines that
immediate CNS specific treatment is not required and is unlikely to be required
during the first cycle of therapy.
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral
load within 6 months prior to registration are eligible for this trial.
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated.
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load.
- 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. To be
eligible for this trial, patients should be class 2B or better.
- Patients does not have a history of active myocarditis.
- Patients does not have a history of any form of pneumonitis or diffuse idiopathic or
immune mediated interstitial pulmonary disease.
- Patient does not have a history of solid organ transplantation.
Study Design
- Phase
- Phase 3
- 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 1 (pembrolizumab) |
Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 42 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, PET/CT or MRI throughout the trial and optionally undergo blood sample collection on study and at disease progression or end of treatment. |
|
|
Experimental Arm 2 (cetuximab, pembrolizumab) |
Patients receive cetuximab IV over 120 minutes on day -14 prior to cycle 1 and then on days 1, 15 and 29 of each cycle and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 42 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, PET/CT or MRI throughout the trial and optionally undergo blood sample collection on study and at disease progression or end of treatment. |
|
Recruiting Locations
Little Rock 4119403, Arkansas 4099753 72205
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501-686-8274
Marysville 5370984, California 5332921 95901
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530-749-4400
Golden 5423294, Colorado 5417618 80401
Boise 5586437, Idaho 5596512 83706
Caldwell 5587698, Idaho 5596512 83605
Coeur d'Alene 5589173, Idaho 5596512 83814
Nampa 5601933, Idaho 5596512 83687
Post Falls 5604353, Idaho 5596512 83854
Sandpoint 5606401, Idaho 5596512 83864
Barrington 4884116, Illinois 4896861 60010
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847-842-4847
Chicago 4887398, Illinois 4896861 60637
Chicago 4887398, Illinois 4896861 60657
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773-296-5360
Crystal Lake 4889229, Illinois 4896861 60014
Decatur 4236895, Illinois 4896861 62526
Decatur 4236895, Illinois 4896861 62526
Downers Grove 4890119, Illinois 4896861 60515
Effingham 4237727, Illinois 4896861 62401
Elgin 4890864, Illinois 4896861 60123
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847-429-2907
Hazel Crest 4895416, Illinois 4896861 60429
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708-799-9995
Libertyville 4899739, Illinois 4896861 60048
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Macomb 4900817, Illinois 4896861 61455
New Lenox 4903535, Illinois 4896861 60451
O'Fallon 4245926, Illinois 4896861 62269
Oak Lawn 4904365, Illinois 4896861 60453-2699
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800-323-8622
Oak Lawn 4904365, Illinois 4896861 60453
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847-384-3621
Peoria 4905687, Illinois 4896861 61615
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217-545-7929
Springfield 4250542, Illinois 4896861 62702
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Springfield 4250542, Illinois 4896861 62781
Crown Point 4919451, Indiana 4921868 46307
Ames 4846834, Iowa 4862182 50010
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Hays 4272782, Kansas 4273857 67601
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Kansas City 4273837, Kansas 4273857 66160
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Olathe 4276614, Kansas 4273857 66061
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Overland Park 4276873, Kansas 4273857 66211
Salina 4278890, Kansas 4273857 67401
Topeka 4280539, Kansas 4273857 66606
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785-295-8000
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Baltimore 4347778, Maryland 4361885 21201
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800-888-8823
Ann Arbor 4984247, Michigan 5001836 48106
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Livonia 4999837, Michigan 5001836 48154
Pontiac 5006166, Michigan 5001836 48341
Ypsilanti 5015688, Michigan 5001836 48197
Bemidji 5017822, Minnesota 5037779 56601
Coon Rapids 5022025, Minnesota 5037779 55433
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Maplewood 5036588, Minnesota 5037779 55109
Minneapolis 5037649, Minnesota 5037779 55407
Saint Louis Park 5045021, Minnesota 5037779 55416
Saint Paul 5045360, Minnesota 5037779 55101
Saint Paul 5045360, Minnesota 5037779 55102
Cape Girardeau 4379966, Missouri 4398678 63703
City of Saint Peters 4407237, Missouri 4398678 63376
Creve Coeur 4382837, Missouri 4398678 63141
Kansas City 4393217, Missouri 4398678 64108
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816-404-4375
Kansas City 4393217, Missouri 4398678 64154
Lee's Summit 4394870, Missouri 4398678 64064
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St Louis 4407066, Missouri 4398678 63110
St Louis 4407066, Missouri 4398678 63129
St Louis 4407066, Missouri 4398678 63136
Anaconda 5637146, Montana 5667009 59711
Billings 5640350, Montana 5667009 59101
Bozeman 5641727, Montana 5667009 59715
Great Falls 5655240, Montana 5667009 59405
Kalispell 5660340, Montana 5667009 59901
Missoula 5666639, Montana 5667009 59804
Cherry Hill 4501198, New Jersey 5101760 08002
Sewell 4504048, New Jersey 5101760 08080
Glens Falls 5118693, New York 5128638 12801
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518-926-6700
Syracuse 5140405, New York 5128638 13210
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Syracuse 5140405, New York 5128638 13215
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Verona 5142333, New York 5128638 13478
Chapel Hill 4460162, North Carolina 4482348 27599
Hendersonville 4470592, North Carolina 4482348 28791
Pinehurst 4485272, North Carolina 4482348 28374
Bismarck 5688025, North Dakota 5690763 58501
Fargo 5059163, North Dakota 5690763 58122
Fargo 5059163, North Dakota 5690763 58122
Sylvania 5173572, Ohio 5165418 43560
Lawton 4540737, Oklahoma 4544379 73505
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Oklahoma City 4544349, Oklahoma 4544379 73104
Ontario 5744166, Oregon 5744337 97914
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Portland 5746545, Oregon 5744337 97225
Allentown 5178127, Pennsylvania 6254927 18103
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Philadelphia 4560349, Pennsylvania 6254927 19114
Mitchell 5229794, South Dakota 5769223 57301
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Sioux Falls 5231851, South Dakota 5769223 57104
Sioux Falls 5231851, South Dakota 5769223 57105
Sioux Falls 5231851, South Dakota 5769223 57117-5134
Yankton 5233053, South Dakota 5769223 57078
Richmond 4781708, Virginia 6254928 23235
Richmond 4781708, Virginia 6254928 23298
Charleston 4801859, West Virginia 4826850 25304
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304-388-9944
Burlington 5247214, Wisconsin 5279468 53105
Cudahy 5249871, Wisconsin 5279468 53110
Germantown 5254218, Wisconsin 5279468 53022
Grafton 5254739, Wisconsin 5279468 53024
Green Bay 5254962, Wisconsin 5279468 54311
Kenosha 5258393, Wisconsin 5279468 53142
La Crosse 5258957, Wisconsin 5279468 54601
Marinette 5261852, Wisconsin 5279468 54143
Milwaukee 5263045, Wisconsin 5279468 53209
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Milwaukee 5263045, Wisconsin 5279468 53233
Mukwonago 5263965, Wisconsin 5279468 53149
Oconomowoc 5265499, Wisconsin 5279468 53066
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262-928-7878
Oshkosh 5265838, Wisconsin 5279468 54904
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Waukesha 5278052, Wisconsin 5279468 53188
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262-928-7632
Waukesha 5278052, Wisconsin 5279468 53188
Wauwatosa 5278159, Wisconsin 5279468 53226
West Allis 5278420, Wisconsin 5279468 53227
More Details
- NCT ID
- NCT06589804
- Status
- Recruiting
- Sponsor
- National Cancer Institute (NCI)
Detailed Description
PRIMARY OBJECTIVE: I. To assess whether the combination of cetuximab and pembrolizumab (arm 2) compared to pembrolizumab alone (arm 1) results in improved overall survival (OS) in subjects with platinum refractory HNSCC. SECONDARY OBJECTIVES: I. To compare pembrolizumab + cetuximab (arm 2) versus (vs.) pembrolizumab alone (arm 1) with respect to objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. II. To compare pembrolizumab + cetuximab (arm 2) vs. pembrolizumab alone (arm 1) with respect to progression free survival (PFS) per RECIST 1.1. III. To evaluate pembrolizumab + cetuximab (arm 2) vs. pembrolizumab alone (arm 1) with respect to duration of response (DOR) per RECIST 1.1. IV. To assess the safety and tolerability of pembrolizumab + cetuximab (arm 2) vs. pembrolizumab alone (arm 1). V. To assess the patient-reported toxicity using Patient Reported Outcomes version of Common Terminology Criteria for Adverse Events (PRO-CTCAE) of pembrolizumab + cetuximab (arm 2) vs. pembrolizumab alone (arm 1). EXPLORATORY OBJECTIVES: I. To identify specific mutational changes that may be indicative of clinical response to pembrolizumab + cetuximab and pembrolizumab alone. II. To evaluate circulating tumor-derived deoxyribonucleic acid (ctDNA) kinetics over the course of treatment in response to pembrolizumab + cetuximab and pembrolizumab alone. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 42 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT), positron emission tomography (PET)/CT or magnetic resonance imaging (MRI) throughout the trial and optionally undergo blood sample collection on study and at disease progression or end of treatment. ARM 2: Patients receive cetuximab IV over 120 minutes on day -14 prior to cycle 1 and then on days 1, 15 and 29 of each cycle and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 42 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, PET/CT or MRI throughout the trial and optionally undergo blood sample collection on study and at disease progression or end of treatment. After completion of study treatment, patients are followed up within 4 weeks and then every 3 and/or 6 months for up to 5 years.