Study To Compare Avelumab In Combination With Standard of Care Chemoradiotherapy (SoC CRT) Versus SoC CRT for Definitive Treatment In Patients With Locally Advanced Squamous Cell Carcinoma Of The Head And Neck (JAVELIN HEAD AND NECK 100)
- Conditions
- Squamous Cell Carcinoma of the Head and Neck
- Interventions
- Other: Chemoradiation
- Registration Number
- NCT02952586
- Lead Sponsor
- Pfizer
- Brief Summary
This is a phase 3 randomized, placebo controlled study to evaluate the safety and anti-tumor activity of Avelumab in combination with standard of care chemoradiation (SoC CRT) versus SoC CRT alone in front-line treatment of patients with locally advanced head and neck cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 697
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + SOC CRT Chemoradiation * Placebo IV matching avelumab: Days 1 of the Lead-in Phase; Days 8, 25, and 39 of the CRT Phase; Q2W for 12 months during the Maintenance Phase * Cisplatin 100 mg/m2 IV: Days 1, 22, and 43 of the CRT Phase * IMRT 70 Gy/35 fractions/7 weeks; 1 fraction per day, 5 fractions/week for 7 weeks during the CRT Phase Avelumab + SOC Chemoradiation Therapy Avelumab * Avelumab 10 mg/kg IV: Day 1 of the Lead-in Phase; Days 8, 25, and 39 of the CRT Phase; and Q2W for 12 months during the Maintenance Phase * Cisplatin 100 mg/m2 IV: Days 1, 22, and 43 of the CRT Phase * Intensity Modulated Radiation Therapy (IMRT) 70 Gy/35 fractions/7 weeks; 1 fraction per day, 5 fractions/week for 7 weeks during the CRT Phase
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) as Assessed by Investigator From randomization until documented PD or death, censored date, whichever occurred first (up to 37 months) PFS was defined as the time (in months) from the date of randomization to the first documentation of objective progressive disease (PD) per modified RECIST v1.1 as assessed by Investigator or death (due to any cause), whichever occurred first. Analysis was performed using Kaplan Meier method. PD refers to any of following: 1) Locoregional PD confirmed by pathology to verify radiographic changes represent true tumor progression and not radiation effects or non-malignant contrast enhancement. 2) Locoregional clinically detectable progression confirmed by pathology. 3) Surgical removal (salvage) of primary tumor with tumor present on final pathology. 4) Salvage neck dissection greater than (\>) 20 weeks after completion of CRT with tumor present on final pathology. 5) Metastatic PD. PFS data was censored on date of last adequate tumor assessment for participants with no PFS event.
- Secondary Outcome Measures
Name Time Method Pathologic Complete Response (pCR) Rate in Participants With Salvage Surgery at the Primary Site From randomization until PD or death (up to 37 months) pCR was defined as the absence of histologically identifiable residual cancer in any resected specimen. The pCR rate at primary site was estimated by dividing the number of participants with pCR recorded at any visit from randomization until PD per modified RECIST v1.1 or death due to any cause by the number of participants randomized who had salvage surgery at the primary site.
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Index Score at CRT Phase and Maintenance Phase Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug) EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated better health status.
Change From Baseline in the European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) VAS Score at CRT Phase and Maintenance Phase Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug) EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated worse health status. In VAS participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status.
Overall Survival (OS) From randomization to the date of death or censored date, whichever occurred first (up to 37 months) Overall survival was defined as the time (in months) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan Meier method.
Number of Participants With Shift From Baseline in Clinical Laboratory Parameters Baseline up to 15 months Grade 1 and 3 ranges are: Anemia:Hb:\<LLN-10.0,\<8.0 g/dL;LC decreased (dec):\<LLN-800/mm\^3,500-200/mm\^3;LC increased (inc):grade 3:\>20,000/mm\^3:NC dec:\<LLN-1500/mm\^3;\<1000-500/mm\^3;PC dec:\<LLN-75,000/mm\^3;\<50,000-25,000/mm\^3;WBC dec:\<LLN-3000/mm\^3;\<2000-1000/mm\^3;ALT inc:\>ULN-3.0\*ULN;\>5.0-20.0\*ULN;ALP \& GGT inc:\>ULN-2.5\*ULN;\>5.0-20.0\*ULN;AST inc:\>ULN-3.0\*ULN;\>5.0-20.0\*ULN;BB inc:\>ULN-1.5\*ULN;\>3.0-10.0\*ULN;CH high:\>ULN-300 mg/dL;\>400-500 mg/dL;CPK inc:\>ULN-2.5\*ULN;\>5\*ULN-10\*ULN;Hypercalcemia:\>ULN-11.5;\>12.5-13.5mg/dL;Hyperglycemia:\>ULN-160; \>250-500mg/dL;Hyperkalemia:\>ULN-5.5;\>6.0-7.0mmol/L;Hypermagnesemia:\>ULN-3.0;\>3.0-8.0 mg/dL;Hypernatremia:\>ULN-150; \>155-160 mmol/L;Hypertriglyceridemia;150-300;\>500-1000 mg/dL;Hypoalbuminemia:\<LLN-3;\<2g/dL;Hypocalcemia:\<LLN-8.0;\<8.0-7.0mg/dL;Hypokalemia:\<LLN-3.0;\<3.0-2.5mmol/L;Hypomagnesemia;\<LLN-1.2;\<0.9-0.7 mg/dL;Hyponatremia:\<LLN-130;\<130-120mmol/L; Hypophosphatemia:\<LLN-2.5;\<2.0-1.0mg/dL;lipase \& serum amylase inc:\>ULN-1.5\*ULN;\>2.0-5.0\*ULN.
Time to Locoregional Failure Per Modified RECIST v1.1 as Assessed by Investigator From the date of randomization to the date of the first documentation of locoregional recurrence or death, whichever occurred first (up to 37 months) Locoregional failure was defined as the time from the date of randomization to the date of the first documentation of locoregional recurrence or death due to any cause per modified RECIST v1.1 as assessed by Investigator, whichever occurred first. Analysis was performed using Kaplan Meier method.
Change From Baseline in Vital Sign - Systolic and Diastolic Blood Pressure Baseline, Lead-in phase: Day1; CRT Phase: Days 1, 8, 22, 25, 39, and 43; Maintenance phase: on Days 1 and 15 in Cycles 1 to 13 and EOT (3 days after the last dose of study drug) Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured in sitting position were reported.
Objective Response Rate (ORR) Per Modified RECIST v1.1 as Assessed by Investigator From randomization until disease progression or death, whichever occurred first (up to 37 months) Objective response (OR) was defined as a complete response (CR) or partial response (PR) per RECIST v1.1 recorded from randomization until disease progression per modified RECIST v1.1 or death due to any cause. A participant was considered to have achieved an OR if the participant had a CR or PR which did not need to be confirmed at a subsequent assessment. CR for target disease: complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis less than \[\<\] 10 millimeter \[mm\]). CR for non-target disease: disappearance of all non-target lesions and normalization of tumor marker levels. All lymph nodes must be 'normal' in size (\<10 mm short axis) . PR: Greater than or equal to (\>=) 30% decrease under baseline of the sum of diameters of all target measurable lesions. The ORR was estimated by dividing the number of participants with OR (CR or PR) by the number of participants randomized.
Time to Distant Metastatic Failure Per Modified RECIST v1.1 as Assessed by Investigator From the date of randomization to the date of the first documentation of distant metastatic or death (up to 37 months) Time to distant metastatic failure or distant metastasis (DM) was defined as the time from the date of randomization to the date of the first documentation of distant metastatic or death due to any cause, whichever occurred first. Distant metastatic disease was defined as new tumor identified at a site distant from the head and neck anatomic region or draining lymph nodes. Analysis was performed using Kaplan Meier method.
Duration of Response (DOR) Per Modified RECIST v1.1 as Assessed by Investigator From the first documentation of objective tumor response to the first documentation of PD or death or censored date, whichever occurred first (up to 37 months) DOR:time from first documentation of objective tumor response (CR/PR) to first documentation of PD/death due to any cause, whichever occurred first.PR:\>=30% decrease under baseline of sum of diameters of all target measurable lesions. CR for target disease:complete disappearance of all target lesions with exception of nodal disease.CR for non-target disease: disappearance of all non-target lesions and normalization of tumor marker levels. PD is any of following:1)Locoregional PD confirmed by pathology to verify radiographic changes denote true tumor progression and not radiation effects or non-malignant contrast enhancement.2)Locoregional clinically detectable progression confirmed by pathology.3)Surgical removal of primary tumor with tumor present on final pathology.4)Salvage neck dissection \>20 weeks after completion of CRT with tumor present on final pathology.5)Metastatic PD. DOR data was censored on date of last adequate tumor assessment for participants with no overall response.
Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC) Baseline (prior to first dose) PD-L1 biomarker expression in tumor tissue as assessed by IHC in the form of positive immune cells and tumor staining cells.
Mean Percentage (%) of Total Tumor Area Occupied by Cluster of Differentiation 8 (CD8+) Cells Baseline (prior to first dose) Description: CD8+ cells are the type of T-lymphocytes. Mean percentage of total tumor area occupied by CD8+ Cells has been reported. Area was measured in millimeter square (mm\^2).
Maximum Plasma Concentration (Cmax) of Avelumab Pre-dose and end of infusion on Day 1 of lead-in phase, Days 8, 25 of CRT phase, Day 1 of Cycle 1 and 2 (each cycle 28 days) Maximum observed plasma concentration (Cmax) of Avelumab is reported.
Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) of Total and Free Cisplatin Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase Area under the plasma concentration time-curve from time zero to the time of last measured concentration (AUClast). AUClast (dn) was calculated by dividing AUClast by the exact dose of cisplastin (in mg) administered to a participant.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 Baseline up to 44 months Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. TEAE was defined as event with onset dates occurring during the on-treatment period.
Percentage of Participants With Positive and Negative Pathology of Neck Dissection From randomization until PD as per investigator assessment (up to 37 months) Percentage of participants with positive and negative pathology of neck dissection were reported. Positive pathology included live tumor cells present or 10% or greater vital tumor tissues. Negative pathology included no live tumor cells present, complete tumor regression, no evidence of vital tumor tissues, less than 10% vital tumor tissue, or not consistent with disease under study.
Time to Attain Maximum Observed Plasma Concentration (Tmax) of Total and Free Cisplatin Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase Time to reach maximum observed plasma concentration (Tmax) of total and free Cisplatin.
Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never and Ever Positive Status Day 1 of lead-in phase and on Days 8 and 25 of CRT phase Change From Baseline in Vital Sign - Pulse Rate Baseline, Lead-in phase: Day1; CRT Phase: Days 1, 8, 22, 25, 39, and 43; Maintenance phase: on Days 1 and 15 in Cycles 1 to 13 and EOT (3 days after the last dose of study drug) Change from baseline in pulse rate in sitting position in beats per minute was reported.
Change From Baseline in National Cancer Comprehensive Network Head and Neck Symptom Index-22 Item Scores (NCCN FHNSI-22) at CRT Phase and Maintenance Phase Baseline, CRT Phase: Days 1 and 29; Maintenance phase: Cycle 1/Day 1, Cycle 3/Day 1, Cycle 7/Day 1, Cycle 7/Day 15, Cycle 11/Day 1, Cycle 11/Day 15, EOT (3 days after the last dose of study drug) The NCCN FHNSI-22 questionnaire measured disease symptoms, treatment side effects and overall quality of life in participants with head and neck cancer. The questionnaire contained 22 items with 5-point Likert scales ranging from 0 to 4 as follows: 'not at all = 0', a little bit = 1, somewhat = 2, quite a bit = 3 and very much = 4. Total score ranged from 0 to 88 where, higher scores represented better symptomatology, quality of life or functioning.
Dose Normalized Maximum Plasma Concentration (Cmax [dn]) of Total and Free Cisplastin Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase Dose normalized (dn) Cmax was calculated by dividing Cmax by the exact dose of total and free Cisplastin (in mg) administered to a participant.
Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status pre-dose on Day 1 up to 30 Days after the end of treatment ADA never-positive was defined as no positive ADA results at any time point; ADA-negative participants (titer less than\< cut point) and ADA ever-positive was defined as at least one positive ADA result at any time point; ADA-positive participants (titer greater than or equal to cut point)
Predose Plasma Concentration (Ctrough) of Avelumab Pre-dose on Day 1 of lead-in phase, Days 8, 25 of CRT phase, Day 1 of Cycle 1, 2, 5, 8, 11 (each cycle 28 days) Ctrough refers to plasma concentration of Avelumab observed just before treatment administration.
Maximum Plasma Concentration (Cmax) of Total and Free Cisplatin Pre-dose, mid-infusion, end of infusion, 3, 4, and 24 hours post dose on Day 1 of CRT phase Maximum observed plasma concentration (Cmax) of total and free Cisplatin is reported.
Trial Locations
- Locations (288)
CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
🇺🇸Bakersfield, California, United States
Compassionate Care Research Group, Inc. at Compassionate Cancer Care Medical Group, Inc.
🇺🇸Riverside, California, United States
University of Maryland, Greenebaum Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Herbert-Herman Cancer Center, Sparrow Hospital
🇺🇸Lansing, Michigan, United States
Radiation Oncology Cancer Services
🇺🇸Allentown, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Stony Brook University
🇺🇸Stony Brook, New York, United States
Memorial Sloan Kettering Cancer Center- Bergen
🇺🇸Montvale, New Jersey, United States
Chris O'Brien Lifehouse Medical Imaging
🇦🇺Camperdown, New South Wales, Australia
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC Shadyside Radiation Oncology
🇺🇸Pittsburgh, Pennsylvania, United States
VA Puget Sound Health Care System
🇺🇸Seattle, Washington, United States
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
Karmanos Cancer Institute
🇺🇸Farmington Hills, Michigan, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
AOU Policlinico Di Modena
🇮🇹Modena, MO, Italy
The West Clinic, PC dba West Cancer Center
🇺🇸Germantown, Tennessee, United States
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
NYU Langone Medical Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center Commack
🇺🇸Commack, New York, United States
Memorial Sloan Kettering Cancer Center Westchester
🇺🇸Harrison, New York, United States
Stony Brook Cancer Center
🇺🇸Stony Brook, New York, United States
Memorial Sloan Kettering Cancer Center: Breast and Imaging Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center- Nassau
🇺🇸Uniondale, New York, United States
Cabinet de radiologie Privé - Dr Joseph Mocaer
🇫🇷Brest, France
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
🇺🇸Duarte, California, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Centro Hospitalar São João, E.P.E
🇵🇹Porto, Portugal
N. N. Blokhin NMRCO
🇷🇺Moscow, Russian Federation
Kansas City VA Radiation Oncology Clinic
🇺🇸Overland Park, Kansas, United States
Klinik fur Radiologie und Nuklearmedizin
🇨🇭Basel, Basel-stadt, Switzerland
Cypress Hematology and Oncology
🇺🇸Parker, Colorado, United States
Klinik fur Strahlentherapie und Radioonkologie
🇨🇭Basel, Basel-stadt, Switzerland
Universitatsspital Basel
🇨🇭Basel, Basel-stadt, Switzerland
Tianjin Cancer Hospital
🇨🇳Tianjin, Tianjin, China
Clinique Hartmann
🇫🇷Neuilly sur Seine, France
Institut Curie
🇫🇷Paris, France
NHS Grampian
🇬🇧Aberdeen, United Kingdom
Rocky Mountain Lions Eye Institute
🇺🇸Aurora, Colorado, United States
University of Colorado Denver CTO/CTRC
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Inpatient Pavilion
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Outpatient Pavilion
🇺🇸Aurora, Colorado, United States
University Of Colorado Hospital Cancer Center
🇺🇸Aurora, Colorado, United States
Cypress Hematology & Oncology
🇺🇸Denver, Colorado, United States
H. Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
Norton Hospital
🇺🇸Louisville, Kentucky, United States
University Medical Center, Inc.
🇺🇸Louisville, Kentucky, United States
Norton Brownsboro Hospital
🇺🇸Louisville, Kentucky, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Department of Radiation Oncology Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
Utah Cancer Specialists
🇺🇸Salt Lake City, Utah, United States
OU Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
University of Oklahoma Health Sciences Center- Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Henry-Joyce Cancer Clinic
🇺🇸Nashville, Tennessee, United States
MUSC SCTR Research Nexus Clinical Science Building
🇺🇸Charleston, South Carolina, United States
MUSC- Ashley River Tower
🇺🇸Charleston, South Carolina, United States
MUSC- Radiation Oncology
🇺🇸Charleston, South Carolina, United States
MUSC- University Hospital
🇺🇸Charleston, South Carolina, United States
UCSD Radiation Oncology South Bay, Cancer Treatment Centers
🇺🇸Chula Vista, California, United States
Tower Hematology Oncology Medical Group
🇺🇸Beverly Hills, California, United States
City of Hope Corona
🇺🇸Corona, California, United States
The Oncology Institute of Hope and Innovation
🇺🇸Whittier, California, United States
Beverly Hills Cancer Center
🇺🇸Beverly Hills, California, United States
UC San Diego Medical Center- La Jolla (Thornton Hospital)
🇺🇸La Jolla, California, United States
Cedars Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
🇺🇸Los Angeles, California, United States
UC San Diego Medical Center- Hillcrest
🇺🇸San Diego, California, United States
City of Hope South Pasadena
🇺🇸South Pasadena, California, United States
UC Irvine Medical Center
🇺🇸Orange, California, United States
Sylvester at Coral Gables
🇺🇸Coral Gables, Florida, United States
Sylvester at Deerfield Beach
🇺🇸Deerfield Beach, Florida, United States
Specialist Global LLC
🇺🇸Hialeah, Florida, United States
City of Hope Antelope Valley
🇺🇸Lancaster, California, United States
Memorial Cancer Institute at Memorial Regional Hospital
🇺🇸Hollywood, Florida, United States
Memorial Cancer Institute at Memorial Hospital West
🇺🇸Pembroke Pines, Florida, United States
Hollis Cancer Center
🇺🇸Lakeland, Florida, United States
Sylvester at Plantation
🇺🇸Plantation, Florida, United States
Ingalls Memorial Hospital
🇺🇸Harvey, Illinois, United States
Primary Healthcare Associates
🇺🇸Tinley Park, Illinois, United States
Ashland-Bellefonte Cancer Center
🇺🇸Ashland, Kentucky, United States
IU Health Arnett Cancer Center
🇺🇸Lafayette, Indiana, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
University of Maryland School of Medicine
🇺🇸Baltimore, Maryland, United States
Highlands Cancer Center
🇺🇸Prestonsburg, Kentucky, United States
Maryland Proton Treatment Center
🇺🇸Baltimore, Maryland, United States
University of Missouri- Ellis Fischel Cancer Center
🇺🇸Columbia, Missouri, United States
Siteman Cancer Center - West County
🇺🇸Creve Coeur, Missouri, United States
Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Washington University School of Medicine Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center- St. Peters
🇺🇸Saint Peters, Missouri, United States
Memorial Sloan Kettering Cancer Center-Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Cancer Center- Monmouth
🇺🇸Middletown, New Jersey, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
University of New Mexico Comprehensive Cancer Center
🇺🇸Albuquerque, New Mexico, United States
NYU Langone Radiology
🇺🇸New York, New York, United States
Bellevue Hospital Center
🇺🇸New York, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸New York, New York, United States
NYU Langone Radiology - Ambulatory Care Center East 41st Street
🇺🇸New York, New York, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
Oncology Specialists of Charlotte, PA
🇺🇸Charlotte, North Carolina, United States
DJL Clinical Research, PLLC
🇺🇸Charlotte, North Carolina, United States
Lehigh Valley Health Network Cancer Center Pharmacy
🇺🇸Allentown, Pennsylvania, United States
Lehigh Valley Health Network-Cedar Crest
🇺🇸Allentown, Pennsylvania, United States
Lehigh Valley Health Network-Muhlenberg
🇺🇸Bethlehem, Pennsylvania, United States
Precision Cancer Research / Gettysburg Cancer Center
🇺🇸Gettysburg, Pennsylvania, United States
PinnacleHealth Cancer Institute
🇺🇸Mechancisburg, Pennsylvania, United States
MUSC- Rutledge Tower
🇺🇸Charleston, South Carolina, United States
The West Clinic PC dba West Cancer Center
🇺🇸Memphis, Tennessee, United States
GHS Cancer Institute
🇺🇸Spartanburg, South Carolina, United States
Texas Oncology El Paso Cancer Treatment Center
🇺🇸El Paso, Texas, United States
Memorial Hermann Hospital - TMC
🇺🇸Houston, Texas, United States
University of Texas Medical Branch
🇺🇸Galveston, Texas, United States
William Beaumont Army Medical Center
🇺🇸El Paso, Texas, United States
UTHealth/Memorial Hermann Cancer Center
🇺🇸Houston, Texas, United States
UTMB Cancer Center at Victory Lakes
🇺🇸League City, Texas, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Chris O'Brien Lifehouse Radiation Oncology Department
🇦🇺Camperdown, New South Wales, Australia
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Northern Sydney Cancer Centre
🇦🇺St Leonards, New South Wales, Australia
Illawarra Shoalhaven Local Health District
🇦🇺Wollongong, New South Wales, Australia
Ordensklinikum Linz GmbH
🇦🇹Linz, Austria
Austin Health
🇦🇺Heidelberg, Victoria, Australia
University Hospital Brussels
🇧🇪Brussels, Belgium
Barwon Health, University Hospital Geelong
🇦🇺Geelong, Victoria, Australia
Grand Hopital de Charleroi - Site Notre-Dame
🇧🇪Charleroi, Belgium
Centre Hospitalier de Jolimont
🇧🇪Haine Saint Paul, Belgium
Site Sainte Elisabeth / CHU UCL Namur
🇧🇪Namur, Belgium
GZA Hospitals Campus Sint Augustinus
🇧🇪Wilrijk, Belgium
CHU de Quebec - Universite Laval
🇨🇦Quebec, Canada
SUN Yat-Sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Cancer Center of Guangzhou Medical University/Oncology Department
🇨🇳Guangzhou, Guangdong, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
Affiliated Tumor Hospital of Guangxi Medical University
🇨🇳Nanning, Guangxi, China
Hai Nan General Hospital
🇨🇳Haikou, Hainan, China
Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology/Cancer Center
🇨🇳Wuhan, Hubei, China
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Liaoning Cancer Hospital & Institute
🇨🇳Shenyang, Liaoning, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Xiangya Hospital Central South University/Oncology Department
🇨🇳Changsha, Hunan, China
Shanghai East Hospital/Oncology Department
🇨🇳Shanghai, Shanghai, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China
West China Hospital of Sichuan University
🇨🇳Chengdu, Sichuan, China
Institut de Cancerologie de l'Ouest (ICO) - Site Paul Papin
🇫🇷Angers cedex 02, France
Institut Sainte Catherine
🇫🇷Avignon cedex 9, France
Hopital Pellegrin - Service de radiologie et d'imagerie
🇫🇷Bordeaux, France
Hopital Saint-Andre
🇫🇷Bordeaux, France
Clinique Pasteur - CFRO
🇫🇷Brest, France
Hopital Franco-Britannique, Institut d'Oncologie Hauts-de-Seine Nord
🇫🇷Levallois-Perret, France
Institut Regional du Cancer Montpellier - Val d'Aurelle
🇫🇷Montpellier cedex 5, France
Hopital prive du Confluent S.A.S.
🇫🇷Nantes cedex 2, France
Hopital prive du Confluent S.A.S
🇫🇷Nantes cedex 2, France
Hopital Americain de Paris
🇫🇷Neuilly Sur Seine, France
Centre Antoine Lacassagne
🇫🇷Nice cedex 2, France
Institut de Cancerologie de l'Ouest (ICO) - Site Rene Gauducheau
🇫🇷Saint Herblain Cedex, France
Centre Hospitalier Prive Saint Gregoire
🇫🇷Saint Gregoire, France
Institut de cancerologie de la Loire Lucien Neuwirth
🇫🇷Saint Priest en Jarez cedex, France
ICANS - Institut de cancerologie Strasbourg Europe
🇫🇷Strasbourg, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Helios Klinikum Berlin-Buch, Institut fur Rontgendiagnostik
🇩🇪Berlin, Buch, Germany
Centre Paul Strauss - Radiologie et medecine nucleaire
🇫🇷Strasbourg Cedex, France
Helios Klinikum Berlin-Buch, Klinik fur Nuklearmedizin
🇩🇪Berlin, Buch, Germany
Helios Klinikum Berlin-Buch, Klinik fur Strahlentherapie
🇩🇪Berlin, Buch, Germany
Helios Klinikum Berlin-Buch
🇩🇪Berlin, Buch, Germany
Universitatsklinikum Dusseldorf
🇩🇪Dusseldorf, Germany
Universitatsklinikum Jena
🇩🇪Jena, Germany
Universitätsklinikum Regensburg
🇩🇪Regensburg, Germany
Attikon University Hospital
🇬🇷Haidari, Attica, Greece
Euromedica General Clinic
🇬🇷Thessaloniki, Greece
General Oncology Hospital of Kifissia "Agioi Anargiroi"
🇬🇷Athens, Attica, Greece
Orszagos Onkologiai Intezet, B Belgyogyaszati Osztaly
🇭🇺Budapest, Hungary
Orszagos Onkologiai Intezet, Sugarterapias Osztaly
🇭🇺Budapest, Hungary
Uzsoki Utcai Korhaz
🇭🇺Budapest, Hungary
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Petz Aladar Megyei Oktato Koraz, Onkoradiologiai osztaly
🇭🇺Gyor, Hungary
Pecsi Tudomanyegyetem, Klinikai Kozpont, Onkoterapias Intezet
🇭🇺Pecs, Hungary
St Luke's Radiation Oncology Network, St Luke's Hospital
🇮🇪Dublin, Ireland
Szegedi Tudomanyegyetem, Szent-Gyorgyi Albert Klinikai Kozpont
🇭🇺Szeged, Hungary
St James's Hospital
🇮🇪Dublin, Ireland
The Chaim Sheba M.C.Tel-Hashomer
🇮🇱Ramat Gan, Israel
St. James's Hospital
🇮🇪Dublin, Ireland
Rabin Medical Center
🇮🇱Petah Tiqva, Israel
Blackrock Clinic
🇮🇪Dublin, Ireland
Rambam Health Care Campus
🇮🇱Haifa, Israel
Hadassah University Hospital, Department of Oncology
🇮🇱Jerusalem, Israel
Istituto Scientifico Romagnolo per lo studio e la cura dei Tumori (I.R.S.T)
🇮🇹Meldola, FC, Italy
ASST degli Spedali Civili di Brescia
🇮🇹Brescia, BS, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
🇮🇹Meldola, FC, Italy
IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
🇮🇹Ravenna, RA, Italy
Ospedale M. Bufalini
🇮🇹Cesena, Forlì-cesena, Italy
Presidio Ospedaliero Vito Fazzi
🇮🇹Lecce, LE, Italy
UOC Oncologia Medica, AUSL della Romagna -RAVENNA
🇮🇹Lugo, RA, Italy
Azienda Ospedaliero-Universitaria di Parma
🇮🇹Parma, PR, Italy
UOC Oncologia Medica, AUSL della Romagna - RAVENNA
🇮🇹Ravenna, RA, Italy
AULSS 9 - Scaligera Ospedale Mater Salutis
🇮🇹Legnago, VR, Italy
Istituto Nazionale Tumori IRCCS - Fondazione Pascale
🇮🇹Napoli, Italy
AUSL - IRCCS and Reggio Emilia
🇮🇹Reggio Emilia, Italy
Aichi cancer center central hospital
🇯🇵Nagoya, Aichi, Japan
National Hospital Organization Shikoku Cancer Center
🇯🇵Matsuyama, Ehime, Japan
Nagoya University Hospital
🇯🇵Nagoya, Aichi, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Hokkaido University Hospital
🇯🇵Sapporo, Hokkaido, Japan
Miyagi Cancer Center
🇯🇵Natori, Miyagi, Japan
Kobe University Hospital
🇯🇵Kobe, Hyogo, Japan
Tohoku University Hospital
🇯🇵Sendai, Miyagi, Japan
Osaka International Cancer Institute
🇯🇵Osaka-shi, Osaka, Japan
Kindai University Hospital
🇯🇵Osakasayama, Osaka, Japan
Saitama Cancer Center
🇯🇵Kita-adachi-gun, Saitama, Japan
Jichi Medical University Hospital
🇯🇵Shimotsuke, Tochigi, Japan
Shizuoka Cancer Center
🇯🇵Sunto-gun, Shizuoka, Japan
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan
Cancer Institute Hospital, Japanese Foundation for Cancer Research
🇯🇵Koto-ku, Tokyo, Japan
Center for Proton Therapy, National Cancer Center
🇰🇷Goyang-si, Gyeonggi-do, Korea, Republic of
Center for Specific Organ Cancer, National Cancer Center
🇰🇷Goyang-si, Gyeonggi-do, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Department of Radiation Oncology, CHA Bundang Medical Center, CHA University
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Hwasun-gun, Jeollanam-do, Korea, Republic of
Department of Radiation Oncology, Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
Division of Radiation Oncology, Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Centrum Onkologii - Instytut im. M. Sklodowskiej - Curie, Klinika Radioterapii i Chemioterapii
🇵🇱Gliwice, Poland
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
Centrum Onkologii im. prof. F. Lukaszczyka
🇵🇱Bydgoszcz, Poland
SPZOZ Ministerstwa Spraw Wewnetrznych i Administracji z Warminsko-Mazurskim Centrum Onkologii
🇵🇱Olsztyn, Poland
NZOZ Provita Prolife Centrum Medyczne
🇵🇱Tomaszow Mazowiecki, Poland
Specjalistyczny Szpital Onkologiczny NU-MED sp. z o.o.
🇵🇱Tomaszow Mazowiecki, Poland
Hospital Pedro Hispano
🇵🇹Matosinhos, Porto, Portugal
CUF Porto
🇵🇹Senhora da Hora, Porto, Portugal
Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE
🇵🇹Vila Nova de Gaia, Porto, Portugal
Instituto Portugues de Oncologia de Coimbra Francisco Gentil, E.P.E.
🇵🇹Coimbra, Portugal
Instituto Portugues de Oncologia do Porto Francisco Gentil, E.P.E.
🇵🇹Porto, Portugal
Centro Hospitalar do Porto, E.P.E.- Hospital de Santo Antonio
🇵🇹Porto, Portugal
Julio Teixeira
🇵🇹Porto, Portugal
SBIH "Chelyabinsk Regional Clinical Centre of Oncology and Nuclear Medicine"
🇷🇺Chelyabinsk, Russian Federation
Budgetary Institution of Healthcare of Omsk Region "Clinical Oncology Dispensary"
🇷🇺Omsk, Russian Federation
FSBI "National Medical Research Center of Oncology n.a. N.N. Petrov"
🇷🇺Saint-Petersburg, Russian Federation
SBIH "SPb Clinical Research Centre of Specialized Kinds of Medical Care (Oncology)"
🇷🇺Saint-Petersburg, Russian Federation
SBHI YaR "Regional Clinical Oncology Hospital"
🇷🇺Yaroslavl, Russian Federation
Hospital Costa del Sol
🇪🇸Marbella, Malaga, Spain
Institut Catala d'Oncologia Badalona, Hospital Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Hospital Universitario Donostia
🇪🇸San Sebastian, Guipuzcoa, Spain
Hospital Clinico Universitario Virgen de la Arrixaca
🇪🇸El Palmar, Murcia, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Spain
Complejo Hospitalario de Jaen
🇪🇸Jaen, Spain
Institut Catala D'Oncologia de Girona
🇪🇸Girona, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Virgen de la Victoria
🇪🇸Malaga, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Fundacion Instituto Valenciano de Oncologia
🇪🇸Valencia, Spain
Hospital Clinico Universitario Lozano Blesa
🇪🇸Zaragoza, Spain
Istituto Oncologico della Svizzera Italiana IOSI, Ospedale San Giovanni
🇨🇭Bellinzona, Ticino, Switzerland
Kantonsspital Winterthur, Medizinische Onkologie
🇨🇭Winterthur, Zuerich, Switzerland
Kantonsspital Winterthur, Radiologie
🇨🇭Winterthur, Zurich, Switzerland
Kantonsspital Winterthur
🇨🇭Winterthur, Zurich, Switzerland
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Vaud, Switzerland
Radiologia ORBV, Ospedale San Giovanni
🇨🇭Bellinzona, Ticino, Switzerland
Institut fur Klinische Pathologie
🇨🇭Zurich, Switzerland
Klinik fur Nuklearmedizin
🇨🇭Zurich, Switzerland
China Medical University Hospital
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Universitatsspital Zurich
🇨🇭Zurich, Switzerland
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Chang Gung Memorial Hospital-Linkou Branch
🇨🇳Taoyuan City, Taiwan
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Bebington, United Kingdom
University Hospital Bristol NHS Foundation Trust
🇬🇧Bristol, United Kingdom
Koo Foundation Sun Yat-Sen Cancer Center
🇨🇳Taipei, Taiwan
Guy's and St. Thomas' NHS Foundation Trust
🇬🇧London, United Kingdom
NHS Lothian, Western General Hospital
🇬🇧Edinburgh, United Kingdom
Medical University of South Carolina- Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
Division of Radiation Oncology, Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
SMG-SNU Boramae Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Kansas City VA Medical Center
🇺🇸Kansas City, Missouri, United States
Montefiore-Einstein Center for Cancer Care
🇺🇸Bronx, New York, United States
Siteman Cancer Center - South County
🇺🇸Saint Louis, Missouri, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Fujian Cancer Hospital
🇨🇳Fuzhou, Fujian, China