Actively Recruiting
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
Led by National Cancer Institute (NCI) · Updated on 2026-05-13
158
Participants Needed
177
Research Sites
244 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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
Official Title
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
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults aged 18 years or older
- Histologically confirmed diagnosis of head and neck squamous cell carcinoma (HNSCC)
- Recurrent and/or metastatic disease not curable by local therapies
- Primary tumor located in oral cavity, oropharynx, larynx, or hypopharynx
- Measurable disease present
- Platinum-refractory disease with progression during or within 29 weeks after definitive or adjuvant therapy
- Tumor positive for PD-L1 with combined positive score (CPS) of 1 or higher
- Completed any radiation therapy at least 10 days before registration
- No prior treatment for recurrent or metastatic disease
- Prior neoadjuvant or induction anti PD-1/PD-L1 or cetuximab allowed if last dose was at least 26 weeks before registration without progression
- No live vaccine within 30 days before registration
- No history of severe hypersensitivity (grade 3 or higher) to pembrolizumab or cetuximab components
- No chronic systemic steroid therapy above 10 mg prednisone equivalent daily within 7 days before registration
- For oropharyngeal cancer, negative HPV status by p16 IHC and/or HPV ISH or CLIA-certified ctHPVDNA assay if tissue unavailable
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- Absolute neutrophil count (ANC) at least 1,500/mm3
- Platelet count at least 100,000/mm3
- Hemoglobin at least 9 g/dL (transfusions allowed to reach this level)
- Creatinine less than or equal to 1.5 times upper limit normal (ULN) or creatinine clearance at least 30 mL/min if above 1.5 x ULN
- Total bilirubin less than or equal to 1.5 x ULN or direct bilirubin below ULN if total bilirubin elevated
- AST/ALT less than or equal to 3 x ULN, or less than 5 x ULN if liver metastases present
- Not pregnant or nursing; negative pregnancy test required for women of childbearing potential within 7 days before registration
- Prior or concurrent malignancies allowed if they do not interfere with safety or efficacy assessments
- Treated or stable brain metastases allowed if no progression on follow-up imaging
- Active brain metastases or leptomeningeal disease allowed if immediate CNS treatment not required and unlikely during first therapy cycle
- HIV-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months prior to registration
- Chronic hepatitis B patients eligible if viral load undetectable on suppressive therapy
- Hepatitis C patients eligible if treated and cured or currently on treatment with undetectable viral load
- Cardiac function assessed as New York Heart Association class 2B or better
- No history of active myocarditis
- No history of pneumonitis or diffuse idiopathic or immune-mediated interstitial lung disease
- No history of solid organ transplantation
You will not qualify if you...
- Primary tumor sites other than oral cavity, oropharynx, larynx, or hypopharynx (e.g., nasopharynx) unless unknown primary approved by study chair
- Pregnancy or nursing
- History of severe hypersensitivity (grade 3 or higher) to pembrolizumab or cetuximab
- Use of chronic systemic steroids exceeding 10 mg prednisone equivalent daily within 7 days before registration
- Active brain metastases requiring immediate CNS treatment
- History of active myocarditis
- History of pneumonitis or diffuse idiopathic or immune-mediated interstitial lung disease
- History of solid organ transplantation
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 177 locations
1
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
Actively Recruiting
2
Fremont - Rideout Cancer Center
Marysville, California, United States, 95901
Active, Not Recruiting
3
VA Palo Alto Health Care System
Palo Alto, California, United States, 94304
Suspended
4
UCHealth Memorial Hospital Central
Colorado Springs, Colorado, United States, 80909
Actively Recruiting
5
Memorial Hospital North
Colorado Springs, Colorado, United States, 80920
Actively Recruiting
6
Poudre Valley Hospital
Fort Collins, Colorado, United States, 80524
Actively Recruiting
7
Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado, United States, 80528
Actively Recruiting
8
Lutheran Hospital - Cancer Centers of Colorado
Golden, Colorado, United States, 80401
Actively Recruiting
9
UCHealth Greeley Hospital
Greeley, Colorado, United States, 80631
Actively Recruiting
10
Medical Center of the Rockies
Loveland, Colorado, United States, 80538
Actively Recruiting
11
Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
Actively Recruiting
12
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, United States, 83706
Actively Recruiting
13
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, United States, 83605
Actively Recruiting
14
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, United States, 83814
Actively Recruiting
15
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, United States, 83687
Actively Recruiting
16
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, United States, 83854
Actively Recruiting
17
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, United States, 83864
Actively Recruiting
18
Advocate Good Shepherd Hospital
Barrington, Illinois, United States, 60010
Actively Recruiting
19
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
Actively Recruiting
20
Advocate Illinois Masonic Medical Center
Chicago, Illinois, United States, 60657
Actively Recruiting
21
AMG Crystal Lake - Oncology
Crystal Lake, Illinois, United States, 60014
Actively Recruiting
22
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, United States, 62526
Actively Recruiting
23
Decatur Memorial Hospital
Decatur, Illinois, United States, 62526
Actively Recruiting
24
Advocate Good Samaritan Hospital
Downers Grove, Illinois, United States, 60515
Actively Recruiting
25
Crossroads Cancer Center
Effingham, Illinois, United States, 62401
Actively Recruiting
26
Advocate Sherman Hospital
Elgin, Illinois, United States, 60123
Actively Recruiting
27
Advocate South Suburban Hospital
Hazel Crest, Illinois, United States, 60429
Actively Recruiting
28
AMG Libertyville - Oncology
Libertyville, Illinois, United States, 60048
Actively Recruiting
29
Condell Memorial Hospital
Libertyville, Illinois, United States, 60048
Actively Recruiting
30
Illinois CancerCare-Macomb
Macomb, Illinois, United States, 61455
Actively Recruiting
31
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, United States, 60451
Actively Recruiting
32
Cancer Care Center of O'Fallon
O'Fallon, Illinois, United States, 62269
Actively Recruiting
33
Advocate Christ Medical Center
Oak Lawn, Illinois, United States, 60453-2699
Actively Recruiting
34
Advocate Outpatient Center - Oak Lawn
Oak Lawn, Illinois, United States, 60453
Actively Recruiting
35
University of Chicago Medicine-Orland Park
Orland Park, Illinois, United States, 60462
Actively Recruiting
36
Advocate High Tech Medical Park
Palos Heights, Illinois, United States, 60463
Actively Recruiting
37
Advocate Lutheran General Hospital
Park Ridge, Illinois, United States, 60068
Actively Recruiting
38
Illinois CancerCare-Peoria
Peoria, Illinois, United States, 61615
Actively Recruiting
39
UW Health Carbone Cancer Center Rockford
Rockford, Illinois, United States, 61114
Actively Recruiting
40
Memorial Hospital East
Shiloh, Illinois, United States, 62269
Actively Recruiting
41
Southern Illinois University School of Medicine
Springfield, Illinois, United States, 62702
Actively Recruiting
42
Springfield Clinic
Springfield, Illinois, United States, 62702
Actively Recruiting
43
Springfield Memorial Hospital
Springfield, Illinois, United States, 62781
Actively Recruiting
44
UChicago Medicine Northwest Indiana
Crown Point, Indiana, United States, 46307
Actively Recruiting
45
Mary Greeley Medical Center
Ames, Iowa, United States, 50010
Actively Recruiting
46
McFarland Clinic - Ames
Ames, Iowa, United States, 50010
Actively Recruiting
47
McFarland Clinic - Boone
Boone, Iowa, United States, 50036
Suspended
48
Mercy Hospital
Cedar Rapids, Iowa, United States, 52403
Actively Recruiting
49
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, United States, 52403
Actively Recruiting
50
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa, United States, 50501
Actively Recruiting
51
McFarland Clinic - Jefferson
Jefferson, Iowa, United States, 50129
Suspended
52
McFarland Clinic - Marshalltown
Marshalltown, Iowa, United States, 50158
Actively Recruiting
53
HaysMed
Hays, Kansas, United States, 67601
Actively Recruiting
54
University of Kansas Cancer Center
Kansas City, Kansas, United States, 66160
Actively Recruiting
55
Lawrence Memorial Hospital
Lawrence, Kansas, United States, 66044
Actively Recruiting
56
The University of Kansas Cancer Center - Olathe
Olathe, Kansas, United States, 66061
Actively Recruiting
57
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, United States, 66210
Actively Recruiting
58
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, United States, 66211
Actively Recruiting
59
Salina Regional Health Center
Salina, Kansas, United States, 67401
Actively Recruiting
60
University of Kansas Health System Saint Francis Campus
Topeka, Kansas, United States, 66606
Actively Recruiting
61
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, United States, 66205
Actively Recruiting
62
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201
Actively Recruiting
63
Boston Medical Center
Boston, Massachusetts, United States, 02118
Actively Recruiting
64
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, United States, 48106
Actively Recruiting
65
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, United States, 48114
Actively Recruiting
66
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, United States, 48188
Actively Recruiting
67
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, United States, 48118
Actively Recruiting
68
Cancer Hematology Centers - Flint
Flint, Michigan, United States, 48503
Actively Recruiting
69
Genesee Hematology Oncology PC
Flint, Michigan, United States, 48503
Suspended
70
Genesys Hurley Cancer Institute
Flint, Michigan, United States, 48503
Actively Recruiting
71
Hurley Medical Center
Flint, Michigan, United States, 48503
Actively Recruiting
72
University of Michigan Health - Sparrow Lansing
Lansing, Michigan, United States, 48912
Actively Recruiting
73
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, United States, 48154
Actively Recruiting
74
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, United States, 48341
Actively Recruiting
75
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, United States, 48197
Actively Recruiting
76
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, United States, 56601
Actively Recruiting
77
Minnesota Oncology - Burnsville
Burnsville, Minnesota, United States, 55337
Actively Recruiting
78
Mercy Hospital
Coon Rapids, Minnesota, United States, 55433
Actively Recruiting
79
Fairview Southdale Hospital
Edina, Minnesota, United States, 55435
Actively Recruiting
80
Saint John's Hospital - Healtheast
Maplewood, Minnesota, United States, 55109
Actively Recruiting
81
Abbott-Northwestern Hospital
Minneapolis, Minnesota, United States, 55407
Actively Recruiting
82
Hennepin County Medical Center
Minneapolis, Minnesota, United States, 55415
Actively Recruiting
83
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, United States, 55416
Actively Recruiting
84
Regions Hospital
Saint Paul, Minnesota, United States, 55101
Actively Recruiting
85
United Hospital
Saint Paul, Minnesota, United States, 55102
Actively Recruiting
86
Saint Francis Medical Center
Cape Girardeau, Missouri, United States, 63703
Actively Recruiting
87
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, United States, 63376
Actively Recruiting
88
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, United States, 63141
Actively Recruiting
89
University Health Truman Medical Center
Kansas City, Missouri, United States, 64108
Actively Recruiting
90
University of Kansas Cancer Center - Briarcliff
Kansas City, Missouri, United States, 64116
Actively Recruiting
91
University of Kansas Cancer Center - North
Kansas City, Missouri, United States, 64154
Actively Recruiting
92
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, United States, 64064
Actively Recruiting
93
Lake Regional Hospital
Osage Beach, Missouri, United States, 65065
Actively Recruiting
94
Washington University School of Medicine
St Louis, Missouri, United States, 63110
Actively Recruiting
95
Mercy Hospital South
St Louis, Missouri, United States, 63128
Actively Recruiting
96
Siteman Cancer Center-South County
St Louis, Missouri, United States, 63129
Actively Recruiting
97
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, United States, 63136
Actively Recruiting
98
Community Hospital of Anaconda
Anaconda, Montana, United States, 59711
Actively Recruiting
99
Billings Clinic Cancer Center
Billings, Montana, United States, 59101
Actively Recruiting
100
Bozeman Health Deaconess Hospital
Bozeman, Montana, United States, 59715
Actively Recruiting
101
Benefis Sletten Cancer Institute
Great Falls, Montana, United States, 59405
Actively Recruiting
102
Logan Health Medical Center
Kalispell, Montana, United States, 59901
Actively Recruiting
103
Community Medical Center
Missoula, Montana, United States, 59804
Actively Recruiting
104
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, United States, 03756
Actively Recruiting
105
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, United States, 07920
Actively Recruiting
106
Jefferson Cherry Hill Hospital
Cherry Hill, New Jersey, United States, 08002
Actively Recruiting
107
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, United States, 07748
Actively Recruiting
108
Memorial Sloan Kettering Bergen
Montvale, New Jersey, United States, 07645
Actively Recruiting
109
Sidney Kimmel Cancer Center Washington Township
Sewell, New Jersey, United States, 08080
Actively Recruiting
110
Memorial Sloan Kettering Commack
Commack, New York, United States, 11725
Actively Recruiting
111
Glens Falls Hospital
Glens Falls, New York, United States, 12801
Actively Recruiting
112
Memorial Sloan Kettering Westchester
Harrison, New York, United States, 10604
Actively Recruiting
113
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Actively Recruiting
114
State University of New York Upstate Medical University
Syracuse, New York, United States, 13210
Actively Recruiting
115
SUNY Upstate Medical Center-Community Campus
Syracuse, New York, United States, 13215
Actively Recruiting
116
Memorial Sloan Kettering Nassau
Uniondale, New York, United States, 11553
Actively Recruiting
117
Upstate Cancer Center at Verona
Verona, New York, United States, 13478
Actively Recruiting
118
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States, 27599
Actively Recruiting
119
Margaret R Pardee Memorial Hospital
Hendersonville, North Carolina, United States, 28791
Actively Recruiting
120
FirstHealth of the Carolinas-Moore Regional Hospital
Pinehurst, North Carolina, United States, 28374
Actively Recruiting
121
Sanford Bismarck Medical Center
Bismarck, North Dakota, United States, 58501
Actively Recruiting
122
Sanford Broadway Medical Center
Fargo, North Dakota, United States, 58122
Actively Recruiting
123
Sanford Roger Maris Cancer Center
Fargo, North Dakota, United States, 58122
Actively Recruiting
124
Miami Valley Hospital South
Centerville, Ohio, United States, 45459
Actively Recruiting
125
Miami Valley Hospital
Dayton, Ohio, United States, 45409
Actively Recruiting
126
Miami Valley Hospital North
Dayton, Ohio, United States, 45415
Actively Recruiting
127
Atrium Medical Center-Middletown Regional Hospital
Franklin, Ohio, United States, 45005-1066
Actively Recruiting
128
Miami Valley Cancer Care and Infusion
Greenville, Ohio, United States, 45331
Actively Recruiting
129
ProMedica Flower Hospital
Sylvania, Ohio, United States, 43560
Actively Recruiting
130
Upper Valley Medical Center
Troy, Ohio, United States, 45373
Actively Recruiting
131
Cancer Centers of Southwest Oklahoma Research
Lawton, Oklahoma, United States, 73505
Actively Recruiting
132
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
Actively Recruiting
133
Saint Alphonsus Cancer Care Center-Ontario
Ontario, Oregon, United States, 97914
Actively Recruiting
134
Providence Willamette Falls Medical Center
Oregon City, Oregon, United States, 97045
Actively Recruiting
135
Providence Portland Medical Center
Portland, Oregon, United States, 97213
Actively Recruiting
136
Providence Saint Vincent Medical Center
Portland, Oregon, United States, 97225
Actively Recruiting
137
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, United States, 18103
Actively Recruiting
138
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, United States, 18017
Actively Recruiting
139
Pocono Medical Center
East Stroudsburg, Pennsylvania, United States, 18301
Actively Recruiting
140
Jefferson Torresdale Hospital
Philadelphia, Pennsylvania, United States, 19114
Actively Recruiting
141
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Actively Recruiting
142
Avera Cancer Institute - Mitchell
Mitchell, South Dakota, United States, 57301
Actively Recruiting
143
Avera Cancer Institute at Pierre
Pierre, South Dakota, United States, 57501
Actively Recruiting
144
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota, United States, 57104
Actively Recruiting
145
Avera Cancer Institute
Sioux Falls, South Dakota, United States, 57105
Actively Recruiting
146
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, United States, 57117-5134
Actively Recruiting
147
Avera Cancer Institute at Yankton
Yankton, South Dakota, United States, 57078
Actively Recruiting
148
Dartmouth Cancer Center - North
Saint Johnsbury, Vermont, United States, 05819
Actively Recruiting
149
VCU Massey Cancer Center at Stony Point
Richmond, Virginia, United States, 23235
Actively Recruiting
150
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States, 23298
Actively Recruiting
151
West Virginia University Charleston Division
Charleston, West Virginia, United States, 25304
Actively Recruiting
152
Aurora Cancer Care-Southern Lakes VLCC
Burlington, Wisconsin, United States, 53105
Actively Recruiting
153
Aurora Saint Luke's South Shore
Cudahy, Wisconsin, United States, 53110
Actively Recruiting
154
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, United States, 54701
Actively Recruiting
155
Aurora Health Care Germantown Health Center
Germantown, Wisconsin, United States, 53022
Actively Recruiting
156
Aurora Cancer Care-Grafton
Grafton, Wisconsin, United States, 53024
Actively Recruiting
157
Aurora BayCare Medical Center
Green Bay, Wisconsin, United States, 54311
Actively Recruiting
158
Aurora Cancer Care-Kenosha South
Kenosha, Wisconsin, United States, 53142
Actively Recruiting
159
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, United States, 54601
Actively Recruiting
160
Aurora Bay Area Medical Group-Marinette
Marinette, Wisconsin, United States, 54143
Actively Recruiting
161
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, United States, 54449
Actively Recruiting
162
Aurora Cancer Care-Milwaukee
Milwaukee, Wisconsin, United States, 53209
Actively Recruiting
163
Aurora Saint Luke's Medical Center
Milwaukee, Wisconsin, United States, 53215
Actively Recruiting
164
Aurora Sinai Medical Center
Milwaukee, Wisconsin, United States, 53233
Actively Recruiting
165
ProHealth D N Greenwald Center
Mukwonago, Wisconsin, United States, 53149
Actively Recruiting
166
ProHealth Oconomowoc Memorial Hospital
Oconomowoc, Wisconsin, United States, 53066
Actively Recruiting
167
Vince Lombardi Cancer Clinic - Oshkosh
Oshkosh, Wisconsin, United States, 54904
Actively Recruiting
168
Aurora Cancer Care-Racine
Racine, Wisconsin, United States, 53406
Actively Recruiting
169
Vince Lombardi Cancer Clinic-Sheboygan
Sheboygan, Wisconsin, United States, 53081
Actively Recruiting
170
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, United States, 54482
Actively Recruiting
171
Aurora Medical Center in Summit
Summit, Wisconsin, United States, 53066
Actively Recruiting
172
Vince Lombardi Cancer Clinic-Two Rivers
Two Rivers, Wisconsin, United States, 54241
Actively Recruiting
173
ProHealth Waukesha Memorial Hospital
Waukesha, Wisconsin, United States, 53188
Actively Recruiting
174
UW Cancer Center at ProHealth Care
Waukesha, Wisconsin, United States, 53188
Actively Recruiting
175
Aurora Cancer Care-Milwaukee West
Wauwatosa, Wisconsin, United States, 53226
Actively Recruiting
176
Aurora West Allis Medical Center
West Allis, Wisconsin, United States, 53227
Actively Recruiting
177
Marshfield Medical Center - Weston
Weston, Wisconsin, United States, 54476
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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