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NCT06589804RecruitingPhase 3

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

Randomized Phase III Trial of Pembrolizumab vs. Pembrolizumab/Cetuximab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma With Platinum Refractory Disease

Source: ClinicalTrials.gov · Last updated 3 Nov 2026

Brief summary (registry, in English)

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.

Status (registry)
Recruiting
Phase (registry)
Phase 3
Study type
Interventional
Enrollment
158 (estimated)
First submitted
6 Sept 2024
Start date
27 Mar 2025
Primary completion date
25 Dec 2032
Lead sponsor
National Cancer Institute (NCI)
NCT number
NCT06589804

What you commit to

  • Study type: Interventional · Phase 3
  • Planned participants: 158
  • From 27 Mar 2025 to the primary completion date, 25 Dec 2032
  • 202 sites in 1 country
  • Visits and tests: ask the trial team, the registry does not list them

Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.

Who cannot take part

Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.

Who the study is looking for

  • 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 ≤ 29 weeks 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 neoadjuvant or induction anti PD-1/PD-L1 monoclonal antibody or cetuximab in the curative setting is allowed if last treatment dose was \>= 26 weeks 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.

Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers

Full criteria on ClinicalTrials.gov

Sites (202)

Sites in registry order. Pick your city on the disease page to sort them by distance.

SiteCityCountrySite status
Lehigh Valley Hospital-Cedar Crest
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AllentownUnited StatesRecruiting
Mary Greeley Medical Center
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AmesUnited StatesRecruiting
McFarland Clinic - Ames
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AmesUnited StatesRecruiting
Community Hospital of Anaconda
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AnacondaUnited StatesRecruiting
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
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Ann ArborUnited StatesRecruiting
Mount Sinai Comprehensive Cancer Center at Aventura
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AventuraUnited StatesRecruiting
University of Maryland/Greenebaum Cancer Center
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BaltimoreUnited StatesRecruiting
Advocate Good Shepherd Hospital
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BarringtonUnited StatesRecruiting
Memorial Sloan Kettering Basking Ridge
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Basking RidgeUnited StatesRecruiting
Sanford Joe Lueken Cancer Center
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BemidjiUnited StatesRecruiting
Lehigh Valley Hospital - Muhlenberg
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BethlehemUnited StatesRecruiting
Billings Clinic Cancer Center
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BillingsUnited StatesRecruiting
Sanford Bismarck Medical Center
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BismarckUnited StatesRecruiting
Saint Alphonsus Cancer Care Center-Boise
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BoiseUnited StatesRecruiting
McFarland Clinic - Boone
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BooneUnited StatesSuspended
Boston Medical Center
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BostonUnited StatesRecruiting
Bozeman Health Deaconess Hospital
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BozemanUnited StatesRecruiting
Trinity Health IHA Medical Group Hematology Oncology - Brighton
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BrightonUnited StatesRecruiting
Aurora Cancer Care-Southern Lakes VLCC
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BurlingtonUnited StatesRecruiting
Minnesota Oncology - Burnsville
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BurnsvilleUnited StatesRecruiting
Saint Alphonsus Cancer Care Center-Caldwell
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CaldwellUnited StatesRecruiting
Trinity Health IHA Medical Group Hematology Oncology - Canton
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CantonUnited StatesRecruiting
Saint Francis Medical Center
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Cape GirardeauUnited StatesRecruiting
Carlisle Regional Cancer Center
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CarlisleUnited StatesRecruiting
Oncology Associates at Mercy Medical Center
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Cedar RapidsUnited StatesRecruiting
Mercy Hospital
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Cedar RapidsUnited StatesRecruiting
Miami Valley Hospital South
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CentervilleUnited StatesRecruiting
UNC Lineberger Comprehensive Cancer Center
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Chapel HillUnited StatesRecruiting
Medical University of South Carolina
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CharlestonUnited StatesRecruiting
Vandalia Health/CAMC Institute for Academic Medicine
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CharlestonUnited StatesRecruiting
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
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ChelseaUnited StatesRecruiting
Jefferson Cherry Hill Hospital
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Cherry HillUnited StatesActive, not recruiting
University of Chicago Comprehensive Cancer Center
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ChicagoUnited StatesRecruiting
Advocate Illinois Masonic Medical Center
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ChicagoUnited StatesRecruiting
Siteman Cancer Center at Saint Peters Hospital
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City of Saint PetersUnited StatesRecruiting
Kootenai Health - Coeur d'Alene
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Coeur d'AleneUnited StatesRecruiting
Memorial Hospital North
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Colorado SpringsUnited StatesRecruiting
UCHealth Memorial Hospital Central
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Colorado SpringsUnited StatesRecruiting
Memorial Sloan Kettering Commack
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CommackUnited StatesRecruiting
Mercy Hospital
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Coon RapidsUnited StatesRecruiting
Siteman Cancer Center at West County Hospital
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Creve CoeurUnited StatesRecruiting
UChicago Medicine Northwest Indiana
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Crown PointUnited StatesRecruiting
AMG Crystal Lake - Oncology
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Crystal LakeUnited StatesRecruiting
Aurora Saint Luke's South Shore
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CudahyUnited StatesRecruiting
Carle at The Riverfront
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DanvilleUnited StatesRecruiting
Miami Valley Hospital
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DaytonUnited StatesRecruiting
Miami Valley Hospital North
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DaytonUnited StatesRecruiting
Cancer Care Specialists of Illinois - Decatur
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DecaturUnited StatesRecruiting
Decatur Memorial Hospital
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DecaturUnited StatesRecruiting
Advocate Good Samaritan Hospital
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Downers GroveUnited StatesRecruiting
Pocono Medical Center
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East StroudsburgUnited StatesRecruiting
Marshfield Medical Center-EC Cancer Center
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Eau ClaireUnited StatesRecruiting
Fairview Southdale Hospital
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EdinaUnited StatesRecruiting
Minnesota Oncology - Edina
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EdinaUnited StatesRecruiting
Carle Physician Group-Effingham
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EffinghamUnited StatesRecruiting
Crossroads Cancer Center
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EffinghamUnited StatesRecruiting
Advocate Sherman Hospital
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ElginUnited StatesRecruiting
UPMC Hillman Cancer Center Erie
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ErieUnited StatesRecruiting
Sanford Roger Maris Cancer Center
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FargoUnited StatesRecruiting
Sanford Broadway Medical Center
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FargoUnited StatesRecruiting
Cancer Hematology Centers - Flint
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FlintUnited StatesRecruiting
Genesee Hematology Oncology PC
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FlintUnited StatesSuspended
Genesys Hurley Cancer Institute
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FlintUnited StatesRecruiting
Hurley Medical Center
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FlintUnited StatesRecruiting
Cancer Care and Hematology-Fort Collins
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Fort CollinsUnited StatesRecruiting
Poudre Valley Hospital
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Fort CollinsUnited StatesRecruiting
McFarland Clinic - Trinity Cancer Center
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Fort DodgeUnited StatesRecruiting
Atrium Medical Center-Middletown Regional Hospital
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FranklinUnited StatesRecruiting
Aurora Health Care Germantown Health Center
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GermantownUnited StatesRecruiting
Glens Falls Hospital
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Glens FallsUnited StatesActive, not recruiting
Lutheran Hospital - Cancer Centers of Colorado
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GoldenUnited StatesRecruiting
Aurora Cancer Care-Grafton
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GraftonUnited StatesRecruiting
Benefis Sletten Cancer Institute
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Great FallsUnited StatesRecruiting
UCHealth Greeley Hospital
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GreeleyUnited StatesRecruiting
Aurora BayCare Medical Center
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Green BayUnited StatesRecruiting
UPMC Cancer Centers - Arnold Palmer Pavilion
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GreensburgUnited StatesRecruiting
Miami Valley Cancer Care and Infusion
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GreenvilleUnited StatesRecruiting
UPMC Pinnacle Cancer Center/Community Osteopathic Campus
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HarrisburgUnited StatesRecruiting
Memorial Sloan Kettering Westchester
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HarrisonUnited StatesRecruiting
HaysMed
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HaysUnited StatesRecruiting
Advocate South Suburban Hospital
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Hazel CrestUnited StatesRecruiting
Margaret R Pardee Memorial Hospital
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HendersonvilleUnited StatesRecruiting
IRMC Cancer Center
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IndianaUnited StatesRecruiting
McFarland Clinic - Jefferson
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JeffersonUnited StatesSuspended
UPMC-Johnstown/John P. Murtha Regional Cancer Center
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JohnstownUnited StatesRecruiting
Logan Health Medical Center
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KalispellUnited StatesRecruiting
University Health Truman Medical Center
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Kansas CityUnited StatesRecruiting
University of Kansas Cancer Center - Briarcliff
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Kansas CityUnited StatesRecruiting
University of Kansas Cancer Center
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Kansas CityUnited StatesRecruiting
University of Kansas Cancer Center - North
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Kansas CityUnited StatesRecruiting
Aurora Cancer Care-Kenosha South
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KenoshaUnited StatesRecruiting
Gundersen Lutheran Medical Center
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La CrosseUnited StatesRecruiting
University of Michigan Health - Sparrow Lansing
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LansingUnited StatesRecruiting
Lawrence Memorial Hospital
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LawrenceUnited StatesRecruiting
Cancer Centers of Southwest Oklahoma Research
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LawtonUnited StatesRecruiting
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
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LebanonUnited StatesRecruiting
University of Kansas Cancer Center - Lee's Summit
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Lee's SummitUnited StatesRecruiting
Liberty Hospital
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LibertyUnited StatesRecruiting
AMG Libertyville - Oncology
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LibertyvilleUnited StatesRecruiting
Condell Memorial Hospital
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LibertyvilleUnited StatesRecruiting
University of Arkansas for Medical Sciences
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Little RockUnited StatesRecruiting
Trinity Health Saint Mary Mercy Livonia Hospital
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LivoniaUnited StatesRecruiting
Medical Center of the Rockies
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LovelandUnited StatesRecruiting
Illinois CancerCare-Macomb
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MacombUnited StatesRecruiting
Saint John's Hospital - Healtheast
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MaplewoodUnited StatesRecruiting
Aurora Bay Area Medical Group-Marinette
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MarinetteUnited StatesRecruiting
McFarland Clinic - Marshalltown
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MarshalltownUnited StatesRecruiting
Marshfield Medical Center-Marshfield
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MarshfieldUnited StatesRecruiting
Fremont - Rideout Cancer Center
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MarysvilleUnited StatesTerminated
Carle Physician Group-Mattoon/Charleston
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MattoonUnited StatesRecruiting
UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion
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MechanicsburgUnited StatesRecruiting
Mount Sinai Medical Center
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Miami BeachUnited StatesRecruiting
Memorial Sloan Kettering Monmouth
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MiddletownUnited StatesRecruiting
Aurora Cancer Care-Milwaukee
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MilwaukeeUnited StatesRecruiting
Aurora Sinai Medical Center
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MilwaukeeUnited StatesRecruiting
Aurora Saint Luke's Medical Center
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MilwaukeeUnited StatesRecruiting
Abbott-Northwestern Hospital
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MinneapolisUnited StatesRecruiting
Hennepin County Medical Center
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MinneapolisUnited StatesRecruiting
Community Medical Center
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MissoulaUnited StatesRecruiting
Avera Cancer Institute - Mitchell
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MitchellUnited StatesRecruiting
UPMC Hillman Cancer Center - Monroeville
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MonroevilleUnited StatesRecruiting
Memorial Sloan Kettering Bergen
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MontvaleUnited StatesRecruiting
ProHealth D N Greenwald Center
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MukwonagoUnited StatesRecruiting
Saint Alphonsus Cancer Care Center-Nampa
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NampaUnited StatesRecruiting
UC Comprehensive Cancer Center at Silver Cross
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New LenoxUnited StatesRecruiting
Memorial Sloan-Kettering Cancer Center
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New YorkUnited StatesRecruiting
Carle Cancer Institute Normal
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NormalUnited StatesRecruiting
Carle BroMenn Medical Center
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NormalUnited StatesRecruiting
Advocate Outpatient Center - Oak Lawn
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Oak LawnUnited StatesRecruiting
Advocate Christ Medical Center
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Oak LawnUnited StatesRecruiting
ProHealth Oconomowoc Memorial Hospital
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OconomowocUnited StatesRecruiting
Cancer Care Center of O'Fallon
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O'FallonUnited StatesRecruiting
University of Oklahoma Health Sciences Center
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Oklahoma CityUnited StatesRecruiting
The University of Kansas Cancer Center - Olathe
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OlatheUnited StatesRecruiting
Saint Alphonsus Cancer Care Center-Ontario
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OntarioUnited StatesRecruiting
Providence Willamette Falls Medical Center
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Oregon CityUnited StatesRecruiting
University of Chicago Medicine-Orland Park
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Orland ParkUnited StatesRecruiting
Lake Regional Hospital
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Osage BeachUnited StatesRecruiting
Vince Lombardi Cancer Clinic - Oshkosh
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OshkoshUnited StatesRecruiting
University of Kansas Hospital-Indian Creek Campus
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Overland ParkUnited StatesRecruiting
University of Kansas Cancer Center-Overland Park
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Overland ParkUnited StatesRecruiting
VA Palo Alto Health Care System
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Palo AltoUnited StatesRecruiting
Advocate High Tech Medical Park
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Palos HeightsUnited StatesRecruiting
Advocate Lutheran General Hospital
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Park RidgeUnited StatesRecruiting
Illinois CancerCare-Peoria
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PeoriaUnited StatesRecruiting
Jefferson Torresdale Hospital
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PhiladelphiaUnited StatesActive, not recruiting
Avera Cancer Institute at Pierre
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PierreUnited StatesRecruiting
FirstHealth of the Carolinas-Moore Regional Hospital
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PinehurstUnited StatesRecruiting
UPMC Hillman Cancer Center
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PittsburghUnited StatesRecruiting
UPMC-Saint Clair Hospital Cancer Center
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PittsburghUnited StatesRecruiting
UPMC-Saint Margaret
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PittsburghUnited StatesRecruiting
UPMC-Passavant Hospital
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PittsburghUnited StatesRecruiting
Trinity Health Saint Joseph Mercy Oakland Hospital
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PontiacUnited StatesRecruiting
Providence Saint Vincent Medical Center
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PortlandUnited StatesRecruiting
Providence Portland Medical Center
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PortlandUnited StatesRecruiting
Kootenai Clinic Cancer Services - Post Falls
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Post FallsUnited StatesRecruiting
Aurora Cancer Care-Racine
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RacineUnited StatesRecruiting
Marshfield Medical Center-Rice Lake
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Rice LakeUnited StatesRecruiting
VCU Massey Comprehensive Cancer Center
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RichmondUnited StatesRecruiting
VCU Massey Cancer Center at Stony Point
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RichmondUnited StatesRecruiting
UW Health Carbone Cancer Center Rockford
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RockfordUnited StatesRecruiting
Dartmouth Cancer Center - North
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Saint JohnsburyUnited StatesRecruiting
Park Nicollet Clinic - Saint Louis Park
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Saint Louis ParkUnited StatesRecruiting
Regions Hospital
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Saint PaulUnited StatesRecruiting
United Hospital
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Saint PaulUnited StatesRecruiting
Salina Regional Health Center
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SalinaUnited StatesRecruiting
Kootenai Clinic Cancer Services - Sandpoint
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SandpointUnited StatesRecruiting
UPMC Cancer Center at UPMC Northwest
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SenecaUnited StatesRecruiting
Sidney Kimmel Cancer Center Washington Township
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SewellUnited StatesActive, not recruiting
Vince Lombardi Cancer Clinic-Sheboygan
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SheboyganUnited StatesRecruiting
Memorial Hospital East
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ShilohUnited StatesRecruiting
Avera Cancer Institute
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Sioux FallsUnited StatesRecruiting
Sanford USD Medical Center - Sioux Falls
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Sioux FallsUnited StatesRecruiting
Sanford Cancer Center Oncology Clinic
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Sioux FallsUnited StatesRecruiting
Springfield Memorial Hospital
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SpringfieldUnited StatesRecruiting
Southern Illinois University School of Medicine
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SpringfieldUnited StatesRecruiting
Springfield Clinic
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SpringfieldUnited StatesRecruiting
Marshfield Medical Center-River Region at Stevens Point
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Stevens PointUnited StatesRecruiting
Siteman Cancer Center-South County
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St LouisUnited StatesRecruiting
Siteman Cancer Center at Christian Hospital
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St LouisUnited StatesRecruiting
Mercy Hospital South
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St LouisUnited StatesRecruiting
Washington University School of Medicine
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St LouisUnited StatesRecruiting
Aurora Medical Center in Summit
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SummitUnited StatesRecruiting
ProMedica Flower Hospital
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SylvaniaUnited StatesRecruiting
State University of New York Upstate Medical University
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SyracuseUnited StatesRecruiting
SUNY Upstate Medical Center-Community Campus
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SyracuseUnited StatesRecruiting
University of Kansas Health System Saint Francis Campus
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TopekaUnited StatesRecruiting
Upper Valley Medical Center
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TroyUnited StatesRecruiting
Vince Lombardi Cancer Clinic-Two Rivers
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Two RiversUnited StatesRecruiting
Memorial Sloan Kettering Nassau
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UniondaleUnited StatesRecruiting
UPMC Cancer Center-Uniontown
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UniontownUnited StatesRecruiting
Carle Cancer Center
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UrbanaUnited StatesRecruiting
Upstate Cancer Center at Verona
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VeronaUnited StatesRecruiting
UPMC Cancer Center-Washington
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WashingtonUnited StatesRecruiting
UW Cancer Center at ProHealth Care
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WaukeshaUnited StatesRecruiting
ProHealth Waukesha Memorial Hospital
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WaukeshaUnited StatesRecruiting
Aurora Cancer Care-Milwaukee West
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WauwatosaUnited StatesRecruiting
Aurora West Allis Medical Center
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West AllisUnited StatesRecruiting
Marshfield Medical Center - Weston
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WestonUnited StatesRecruiting
University of Kansas Hospital-Westwood Cancer Center
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WestwoodUnited StatesRecruiting
Avera Cancer Institute at Yankton
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YanktonUnited StatesRecruiting
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
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YpsilantiUnited StatesRecruiting

This page is information, not medical advice. Discuss any trial with your doctor.