A Study of Napabucasin Plus Nab-Paclitaxel With Gemcitabine in Adult Patients With Metastatic Pancreatic Adenocarcinoma
- Conditions
- Carcinoma, Pancreatic Ductal
- Interventions
- Registration Number
- NCT02993731
- Lead Sponsor
- Sumitomo Pharma America, Inc.
- Brief Summary
This is a randomized, open-label, multi-center, phase 3 study of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine for adult patients with Metastatic Pancreatic Ductal Adenocarcinoma.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1134
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Written, signed consent for trial participation must be obtained from the patient appropriately in accordance with applicable International Conference on Harmonization (ICH) guidelines and local and regulatory requirements prior to the performance of any study specific procedure.
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Must have histologically or cytologically confirmed advanced pancreatic ductal adenocarcinoma (PDAC) that is metastatic. The definitive diagnosis of metastatic PDAC will be made by integrating the histopathological data within the context of the clinical and radiographic data. Patients with islet cell neoplasms are excluded.
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Must not have previously received chemotherapy or any investigational agent for the treatment of PDAC. A fluoropyrimidine or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed for as long as last dose was administered > 6 months prior to randomization and no lingering toxicities are present.
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Nab-paclitaxel with gemcitabine therapy is appropriate for the patient and recommended by the Investigator.
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Patient has one or more metastatic tumors evaluable by CT scan with contrast (or MRI, if patient is allergic to CT contrast media) per RECIST 1.1. Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as necessary to document all sites of disease must be performed within 14 days prior to randomization. Qualifying scans performed as part of standard of care prior to patient signature of the study informed consent will be acceptable as baseline scanning as long as scanning is performed < 14 days prior to randomization.
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Must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1, assessed within 14 days prior to randomization. Two observers qualified to perform assessment of the performance status will be required to perform this assessment. If discrepant, the one with the most deteriorated performance status will be considered true.
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Must have life-expectancy of > 12 weeks.
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Must be ≥ 18 years of age. Due to increased risk of sepsis in patients >80 years old, candidate patients in this age group should be thoroughly evaluated prior to study randomization to ensure they are fit to receive chemotherapy. In addition to all of the inclusion/exclusion criteria listed, clinical judgment should be used regarding patients' susceptibility to infection (including but not limited to presence of ascites or diabetes mellitus increasing risk of infection). Furthermore, the expected stability of their performance status while receiving repeat weekly chemotherapy cycles should be given special attention. Patients in this age group should not be randomized on the study should there be any hesitation on any of these considerations.
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For male or female patients of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 180 days after the final dose of nab-paclitaxel and gemcitabine or for 30 days for female patients and for 90 days for male patients, after the final napabucasin dose if nab-paclitaxel and gemcitabine were not administered.
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Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 5 days prior to randomization.
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Patient has adequate biological parameters as demonstrated by the following blood counts at baseline (obtained < 14 days prior to randomization; laboratory testing performed as part of standard of care prior to patient signature of informed consent for the study will be acceptable as baseline laboratory work as long as testing is performed < 14 days prior to randomization):
- Absolute neutrophil count (ANC) > 1.5 x 10^9/L
- Platelet count > 100,000/mm^3 (100 x 10^9/L). Must not have required transfusion of platelets within 1 week of baseline platelet count assessment.
- Hemoglobin (HgB) > 9 g/dL. Must not have required transfusion of red blood cells within 1 week of baseline Hgb assessment.
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Patient has the following blood chemistry levels at baseline (obtained < 14 days prior to randomization; laboratory testing performed as part of standard of care prior to patient signature of informed consent for the study will be acceptable as baseline laboratory work as long as testing is performed < 14 days prior to randomization):
- AST (SGOT) and ALT (SGPT) ≤ 2.5 × institutional upper limit of normal (ULN) [≤ 5 × ULN in presence of liver metastases]
- Total bilirubin ≤ 1.5 x institutional ULN. If total bilirubin is > ULN and < 1.5 x ULN, it must be non-rising for at least 7 days.
- Serum creatinine within normal limits or calculated clearance > 60 mL/min/1.73 m^2 for patients with serum creatinine levels above or below the institutional normal value. If using creatinine clearance, actual body weight should be used for calculating creatinine clearance (eg. Using the Cockcroft-Gault formula). For patients with a Body Mass Index (BMI) > 30 kg/m^2, lean body weight should be used instead.
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Patient not on anticoagulation has acceptable coagulation studies (obtained < 14 days prior to randomization; laboratory testing performed as part of standard of care prior to patient signature of informed consent for the study will be acceptable as baseline laboratory work as long as testing is performed < 14 days prior to randomization) as demonstrated by prothrombin time (PT) and partial thromboplastin time (PTT) below or within normal limits (+15%).
Patients on anticoagulation must have coagulation values within the therapeutic range appropriate for the anti-coagulation indication.
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Patient has no clinically significant abnormalities on urinalysis results (obtained < 14 days prior to randomization; laboratory testing performed as part of standard of care prior to patient signature of informed consent for the study will be acceptable as baseline laboratory work as long as testing is performed < 14 days prior to randomization).
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Patient must have adequate nutritional status with Body Mass Index (BMI) > 18 kg/m^2 and body weight of > 40 kg with serum albumin > 3 g/dL.
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Baseline laboratory evaluations must be done within 14 days prior to randomization and some must be repeated < 72 hours prior to randomization.
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Patients requiring biliary stent placement must have biliary stent placed > 7 days prior to screening.
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Pain symptoms should be stable (of tolerable Grade 2 or less).
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Only patients with available archival tumor tissue must consent to provision of, and Investigator(s) must confirm access to and agree to submit a representative formalin fixed paraffin block of tumor tissue in order that the specific correlative marker assays (Correlative Studies) of this protocol may be conducted. Submission of the tissue does not have to occur prior to randomization. Where local center regulations prohibit submission of blocks of tumor tissue, two 2 mm cores of tumor from the block and 5-20 unstained slides of whole sections of representative tumor tissue are preferred. Where it is not possible to obtain two 2 mm cores of tumor from the block, 5-20 unstained slides of representative tumor tissue are also acceptable. Where no previously resected or biopsied tumor tissue exists or is available, on the approval of the Sponsor/designated CRO, the patient may still be considered eligible for the study.
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Patient must consent to provision of a sample of blood in order that the specific correlative marker assays (Correlative Studies) may be conducted.
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Patients must be accessible for treatment and follow up. Patients registered on this trial must receive protocol treatment and be followed at the participating center. This implies there must be reasonable geographical limits placed on patients being considered for this trial. Investigators must ensure that the patients randomized on this trial will be available for complete documentation of the treatment, response assessment, adverse events, and follow-up.
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Protocol treatment is to begin within 2 calendar days of patient randomization for patients randomized to Arm 1. Patients randomized to Arm 2 must begin protocol treatment within 7 calendar days of randomization.
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The patient is not receiving therapy in a concurrent clinical study and the patient agrees not to participate in other interventional clinical studies during their participation in this trial while on study treatment. Patients participating in surveys or observational studies are eligible to participate in this study.
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Patients with no evidence of metastatic disease as well as patients with a local recurrence following surgical resection of primary lesion.
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Patient has experienced a decline in ECOG performance status between Baseline visit and within 72 hours prior to randomization.
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Patient has a > 20% decrease in serum albumin level between Baseline visit and within 72 hours prior to randomization.
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Patient has a > 10% decrease in weight between Baseline visit and within 72 hours prior to randomization.
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Any prior anti-cancer chemotherapy, biologic or investigational therapy for PDAC.
- Patients receiving immunotherapy for non-cancer related treatment within < 4 weeks of first planned dose of study treatment will be excluded.
- A fluoropyrimidine or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed for as long as last dose was administered > 6 months prior to randomization.
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Major surgery within 4 weeks prior to randomization.
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Any known brain or leptomeningeal metastases are excluded, even if treated.
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Patients with clinically significant ascites or pleural effusions.
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Women who are pregnant or breastfeeding. Women should not breastfeed while taking study treatment and for 4 weeks after the last dose of napabucasin or while undergoing treatment with nab-paclitaxel and gemcitabine and for 180 days after the last dose of nab-paclitaxel and gemcitabine.
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Gastrointestinal disorder(s) which, in the opinion of the Principal Investigator, would significantly impede the absorption of an oral agent (e.g. active Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection).
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Unable or unwilling to swallow napabucasin capsules daily.
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Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.
- History of cardiac disease: congestive heart failure (CHF) > New York Heart Association (NYHA) Class II; active coronary artery disease, myocardial infarction or coronary stenting within 6 months prior to randomization; unevaluated new onset angina within 3 months or unstable angina (angina symptoms at rest) or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).
- Current uncontrolled hypertension (systolic blood pressure [BP] > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management) as well as prior history of hypertensive crisis or hypertensive encephalopathy.
- Significant vascular disease (e.g., aortic aneurysm, aortic dissection, symptomatic peripheral vascular disease including claudication, Leo Buerger's disease). Treated peripheral vascular disease that is stable for at least 6 months is allowed.
- Evidence of bleeding diathesis or clinically significant coagulopathy.
- Major surgical procedure (including open biopsy, significant traumatic injury, etc.) within 28 days, or anticipation of the need for major surgical procedure during the course of the study as well as minor surgical procedure (excluding placement of a vascular access device or bone marrow biopsy) within 7 days prior to randomization.
- Patients with clinically significant abnormalities on urinalysis at < 14 days prior to randomization.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization.
- Ongoing serious, non-healing wound, ulcer, or bone fracture.
- Known infection with Human Immunodeficiency Virus (HIV), and/or active infection with hepatitis B, or hepatitis C.
- History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.
- History of hemolytic-uremic syndrome.
- History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa).
- Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders that could compromise the patient's safety or the study data integrity.
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Known hypersensitivity to gemcitabine, taxanes or any of their excipients, or the patient exhibits any of the events outlined in the Contraindications or Special Warnings and Precautions sections of the product or comparator Summary of Product Characteristics or Prescribing Information. Possible hypersensitivity to napabucasin or one of the excipients which include the azo dyes sunset yellow and allura red.
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Neurosensory neuropathy > grade 2 at baseline.
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Uncontrolled chronic diarrhea > grade 2 at baseline.
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Patients being treated with Warfarin.
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Patients with active, uncontrolled bacterial, viral or fungal infection(s) requiring systemic therapy
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Patients with a history of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated by surgery alone or surgery plus radiotherapy with no evidence of disease continuously for > 5 years.
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Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.
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Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol, including patients with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol. Patients planning to take a vacation for 14 or more consecutive days during the course of the study are ineligible.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: Napabucasin plus Nab-paclitaxel with Gemcitabine Nab-paclitaxel Patients randomized to this arm will receive napabucasin administered orally, twice daily in combination with weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks. Arm 2: Nab-paclitaxel with Gemcitabine Nab-paclitaxel Patients randomized to this arm will receive weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks. Arm 2: Nab-paclitaxel with Gemcitabine Gemcitabine Patients randomized to this arm will receive weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks. Arm 1: Napabucasin plus Nab-paclitaxel with Gemcitabine Gemcitabine Patients randomized to this arm will receive napabucasin administered orally, twice daily in combination with weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks. Arm 1: Napabucasin plus Nab-paclitaxel with Gemcitabine Napabucasin Patients randomized to this arm will receive napabucasin administered orally, twice daily in combination with weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.
- Primary Outcome Measures
Name Time Method Overall Survival From 4 weeks after the patient has been off study therapy, every 4 weeks thereafter for 6 months, then every 3 months thereafter until death, the study closes or 3 years since treatment discontinuation. To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Overall Survival of patients with metastatic pancreatic ductal adenocarcinoma.
- Secondary Outcome Measures
Name Time Method Progression Free Survival From date of randomization, every 8 weeks, until the date of first documented objective disease progression, up to 36 months To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Progression Free Survival (PFS) of patients with metastatic pancreatic ductal adenocarcinoma. PFS is defined as the time from randomization to the first objective documentation of disease progression or death due to any cause.
Disease Control Rate From date of randomization, every 8 weeks, until the date of first documented objective disease progression, up to 36 months To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Disease Control Rate (DCR) of patients with metastatic pancreatic ductal adenocarcinoma. DCR is defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.
Overall Response Rate From date of randomization, every 8 weeks, until the date of first documented objective disease progression, up to 36 months To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Overall Response Rate (ORR) of patients with metastatic pancreatic ductal adenocarcinoma. ORR is evaluated using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1).
Number of Patients With Adverse Events Every 1-2 weeks from date of screening until protocol treatment discontinuation. Following permanent protocol treatment discontinuation, every 8 weeks, starting with the 4 week post-protocol treatment discontinuation visit, up to 36 months. All patients who have received at least one dose of napabucasin will be included in the safety analysis according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.0. The incidence of adverse events will be summarized by type of adverse event and severity.
Mean Change From Baseline for Global Quality of Life (QoL) at 8 Weeks. 8 weeks QoL will be measured using the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ-C30) in patients with metastatic pancreatic ductal adenocarcinoma with napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine. EORTQ QLC-C30 is a questionnaire used to assess the overall quality of life in cancer patients - 28 questions use a 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions use a 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged and transformed to 0-100 scale; higher overall score = better quality of life.
Trial Locations
- Locations (261)
Comprehensive Blood and Cancer Center
🇺🇸Bakersfield, California, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
Montefiore Cancer Center
🇺🇸Bronx, New York, United States
Centro Hospitalar Lisboa Norte
🇵🇹Lisbon, Portugal
Indiana University - Melvin and Bren Simon Cancer
🇺🇸Indianapolis, Indiana, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Przychodnia Lekarska KOMED
🇵🇱Konin, Poland
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Clearview Cancer Institute (CCI)
🇺🇸Huntsville, Alabama, United States
Kaiser Permanente - Vallejo Medical Center
🇺🇸Vallejo, California, United States
Norwalk Hospital The C Anthony and Jean Whittingham Cancer Center
🇺🇸Norwalk, Connecticut, United States
The C Anthony and Jean Whittingham Cancer Center
🇺🇸Norwalk, Connecticut, United States
Louisiana Hematology Oncology Associates (LHOA)
🇺🇸Baton Rouge, Louisiana, United States
Cotton O'Neil Cancer Center
🇺🇸Topeka, Kansas, United States
Carle Cancer Center CCOP
🇺🇸Urbana, Illinois, United States
Los Angeles Hematology Oncology Medical Group
🇺🇸Los Angeles, California, United States
Mayo Clinic Cancer Center
🇺🇸Jacksonville, Florida, United States
UCLA Medical Center Santa Monica Hematology And Oncology
🇺🇸Santa Monica, California, United States
Northwestern Medicine Regional Medical Group
🇺🇸Warrenville, Illinois, United States
Cancer Specialists of North Florida
🇺🇸Jacksonville, Florida, United States
Weill Cornell Medicine/ NewYork-Presbyterian
🇺🇸New York, New York, United States
Parkview Physician Group (PPG)
🇺🇸Fort Wayne, Indiana, United States
Maine Center for Cancer Medicine - Scarborough
🇺🇸Scarborough, Maine, United States
University of Southern California
🇺🇸Los Angeles, California, United States
UNM Cancer Research and Treatment Center
🇺🇸Albuquerque, New Mexico, United States
Metro MN Clinical Oncology Research Consortium
🇺🇸Saint Louis Park, Minnesota, United States
St. Luke's Hospital of Duluth
🇺🇸Duluth, Minnesota, United States
Saint Alphonsus Health System
🇺🇸Boise, Idaho, United States
Cancer Center of Kansas
🇺🇸Wichita, Kansas, United States
St. Vincent Frontier Cancer Center
🇺🇸Billings, Montana, United States
UMass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Jackson Oncology Associates
🇺🇸Jackson, Mississippi, United States
Ingalls Cancer Research Center
🇺🇸Harvey, Illinois, United States
Florida Cancer Specialists & Research Institute
🇺🇸Fort Myers, Florida, United States
Greater Baltimore Medical Center
🇺🇸Baltimore, Maryland, United States
Gabrail Cancer Center (GCC) - Canton Facility
🇺🇸Canton, Ohio, United States
Southeastern Medical Oncology Center
🇺🇸Goldsboro, North Carolina, United States
University of Missouri - Ellis Fischel Cancer Cent
🇺🇸Columbia, Missouri, United States
Stony Brook University
🇺🇸Stony Brook, New York, United States
FirstHealth Outpatient Cancer Center
🇺🇸Pinehurst, North Carolina, United States
Tennessee Oncology Chattanooga
🇺🇸Chattanooga, Tennessee, United States
Cone Health Cancer Center
🇺🇸Greensboro, North Carolina, United States
Kaiser Permanente - Westside Medical Office
🇺🇸Hillsboro, Oregon, United States
UZ Ghent
🇧🇪Gent, Belgium
Fox Chase Cancer Center (FCCC) - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
The Center for Cancer and Blood Disorders
🇺🇸Fort Worth, Texas, United States
Avera Medical Group
🇺🇸Sioux Falls, South Dakota, United States
North Shore Hematology Oncology Associates PC
🇺🇸East Setauket, New York, United States
Toledo Clinic Cancer Centers
🇺🇸Toledo, Ohio, United States
ICON Cancer Care
🇦🇺South Brisbane, Australia
Bon Secours Cancer Institute Medical Oncology
🇺🇸Midlothian, Virginia, United States
Cancer Center of Southwest Oklahoma
🇺🇸Lawton, Oklahoma, United States
Prince of Wales Private Hospital
🇦🇺Randwick, Australia
Sydney Adventist Hospital
🇦🇺Wahroonga, Australia
Dr. Everett Chalmers Regional Hospital
🇨🇦Fredericton, New Brunswick, Canada
Landeskrankenhaus Medical University Innsbruck
🇦🇹Innsbruck, Austria
Universitatsklinik far Innere Medizin III
🇦🇹Salzburg, Austria
Medical University Vienna
🇦🇹Vienna, Austria
MultiCare Institute for Research and Innovation
🇺🇸Tacoma, Washington, United States
Green Bay Oncology, Ltd. - West Green Bay
🇺🇸Green Bay, Wisconsin, United States
The Austin Hospital
🇦🇺Heidelberg, Australia
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Australia
UZ Leuven
🇧🇪Leuven, Belgium
Macquarie University Hospital
🇦🇺Sydney, Australia
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States
The Tweed Hospital
🇦🇺Tweed Heads, Australia
University of Toronto - St. Michael's Hospital
🇨🇦Toronto, Canada
Cabrini Hospital
🇦🇺Malvern, Australia
Blacktown Cancer and Haematology Centre
🇦🇺Blacktown, Australia
LKH Universitätsklinikum Graz
🇦🇹Graz, Austria
The Everett Clinic
🇺🇸Everett, Washington, United States
Cross Cancer Institute
🇨🇦Edmonton, Canada
ULB Erasme
🇧🇪Bruxelles, Belgium
Antwerp University Hospital
🇧🇪Edegem, Belgium
UZ Brussel
🇧🇪Jette, Belgium
Onkologické oddělení
🇨🇿Zlín, Czechia
CHU-Hôtel Dieu
🇫🇷Nantes Cedex 1, France
Cancer Center of Guangzhou Medical University
🇨🇳Guangzhou, China
Guangdong General Hospital
🇨🇳Guangzhou, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, China
The Second Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, China
Fondazione Poliambulanza
🇮🇹Brescia, Italy
Fakultni nemocnice Brno Interni hematoonkologicka klinika
🇨🇿Brno, Czechia
Gesundheitszentrum St. Marien GmbH
🇩🇪Amberg, Germany
Klinikum Chemnitz
🇩🇪Chemnitz, Germany
Universitätsmedizin Mannheim
🇩🇪Mannheim, Germany
University Hospital Bonn
🇩🇪Bonn, Germany
Medizinische Hochschule
🇩🇪Hannover, Germany
University Hospital Olomouc
🇨🇿Olomouc, Czechia
Hôpital Sud - CHU Amiens Picardie
🇫🇷Amiens, France
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan
Dermatological Hospital San Lazzaro
🇮🇹Torino, Italy
ASST Settelaghi
🇮🇹Varese, Italy
Institute de Cancerologie de Lorraine
🇫🇷Vandœuvre-lès-Nancy, France
Chonnam National University Hwasun Hospital
🇰🇷Jeongnam, Korea, Republic of
Aichi Cancer Center Hospital
🇯🇵Nagoya, Aichi, Japan
Centre Eugene Marquis
🇫🇷Rennes, France
Krankenhaus Nordwest
🇩🇪Frankfurt am main, Germany
Osaka International Cancer Institute
🇯🇵Osaka, Japan
Hopital Europeen Georges Pompidou
🇫🇷Paris, France
Hopital Edourard Herriot
🇫🇷Lyon Cedex 03, France
Hopital Civil de strasbourg
🇫🇷Strasbourg, France
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Klinikum Bogenhausen
🇩🇪München, Germany
Kursk Regional Clinical Oncology Dispensary
🇷🇺Kislino, Kursk, Russian Federation
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
Zuyderland Medical Center
🇳🇱Sittard, Netherlands
Santa Maria de Prato Hospital
🇮🇹Feltre, Italy
Centrum Onkologii-Instytut im.M.Sklodowskiej-Curie
🇵🇱Gliwice, Poland
IRCCS Ospedale San Raffaele
🇮🇹Milano, Italy
Onkologicke oddeleni
🇨🇿Benešov, Czechia
Centre Antoine Lacassagne
🇫🇷Nice, France
Klinikum Oldenburg AöR - UK für Innere Medizin
🇩🇪Oldenburg, Germany
Seoul national University Bundang Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Clinique Saint Anne
🇫🇷Strasbourg, France
Klinika Chirurgii Onkologicznej
🇵🇱Lublin, Poland
Poitiers University Hospital
🇫🇷Poitiers, France
SLK-Kliniken Heilbronn GmbH
🇩🇪Heilbronn, Germany
AOU Mater Domini
🇮🇹Catanzaro, Italy
Shikoku Cancer Center
🇯🇵Matsuyama, Ehime, Japan
Ospedale degli Infermi
🇮🇹Rimini, Italy
Hokkaido University Hospital
🇯🇵Sapporo, Hokkaido, Japan
University of Tokyo Hospital
🇯🇵Bunkyō-Ku, Tokyo, Japan
Medisch Centrum Leeuwarden (MCL)
🇳🇱Leeuwarden, Netherlands
Istituto Ricerca e la Cura del Cancro (IRCC)
🇮🇹Candiolo, Italy
Kanagawa Cancer Center
🇯🇵Yokohama, Kanagawa, Japan
AO SM Misericordia
🇮🇹Perugia, Italy
Saitama Cancer Center
🇯🇵Saitama, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Samodzielny Publiczny Szpital Kliniczny
🇵🇱Poznań, Poland
Wojewodzki Szpital Zespolony
🇵🇱Toruń, Poland
Llc Evimed
🇷🇺Chelyabinsk, Russian Federation
Hospital da Luz
🇵🇹Lisboa, Portugal
Republican Clinical Oncology Dispensary
🇷🇺Cheboksary, Russian Federation
Centro Hospitalar Entre Douro e Vouga
🇵🇹Santa Maria Da Feira, Portugal
Tan Tock Seng Hospital
🇸🇬Singapore, Singapore
Railway Clinical Hospital on station Chelyabinsk
🇷🇺Chelyabinsk, Russian Federation
Arkhangelsk Regional Clinical Oncology Dispensary
🇷🇺Arkhangel'sk, Russian Federation
N.N. Blokhin Russian Cancer Research Center
🇷🇺Moscow, Russian Federation
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Clínico y Provincial de Barcelona
🇪🇸Barcelona, Spain
Zaytsev Institute General and Urgent Surgery of National Academy Medical Science of Ukraine
🇺🇦Kharkiv, Ukraine
National Institute of Cancer
🇺🇦Kyiv, Ukraine
CHU Dinant Godinne
🇧🇪Yvoir, Belgium
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Mercy Clinic Oncology and Hematology - McAuley
🇺🇸Oklahoma City, Oklahoma, United States
SCRI - Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Jilin Cancer Hospital
🇨🇳Changchun, China
Beijing Cancer Hospital
🇨🇳Beijing, China
The first hospital of jilin university
🇨🇳Changchun, China
The First Affiliated Hospital Zhejiang University
🇨🇳Hangzhou, China
Sir Run Shaw Hospital School of Medicine Zhejiang University
🇨🇳Hangzhou, China
The First Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, China
The Affiliated Hospital of Qingdao University
🇨🇳Qingdao, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
Huashan Hospital
🇨🇳Shanghai, China
Ren Ji Hospital Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, China
East Hospital of Tongji University
🇨🇳Shanghai, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, China
General Hospital of Ningxia Medical University
🇨🇳Yinchuan, China
Henan Cancer Hospital
🇨🇳Zhengzhou, China
UAB Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
OHSU Knight Cancer Institute
🇺🇸Portland, Oregon, United States
IRCCS - Studio e la Cura dei Tumori
🇮🇹Meldola, Italy
Tochigi Cancer Center
🇯🇵Utsunomiya, Tochigi, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Aurora St. Luke's Medical Center - Vince Lombardi
🇺🇸Milwaukee, Wisconsin, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Highlands Oncology Group
🇺🇸Fayetteville, Arkansas, United States
Hospital Universitario Germans Trias i Pujol
🇪🇸Barcelona, Spain
Torrance Health Association DBA Torrance Memorial
🇺🇸Redondo Beach, California, United States
Helen F. Graham Cancer Center
🇺🇸Newark, Delaware, United States
St. Joseph Hospital of Orange
🇺🇸Orange, California, United States
Georgetown University Medical Center (GUMC)
🇺🇸Washington, District of Columbia, United States
Memorial Regional Hospital
🇺🇸Hollywood, Florida, United States
Mount Sinai Medical Center
🇺🇸Miami Beach, Florida, United States
Florida Cancer Specialists North
🇺🇸Saint Petersburg, Florida, United States
Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Florida Cancer Specialists East Region
🇺🇸Wellington, Florida, United States
NorthShore University Health Systems
🇺🇸Evanston, Illinois, United States
University Cancer & Blood Center
🇺🇸Athens, Georgia, United States
Columbus Regional Research Institute
🇺🇸Columbus, Georgia, United States
Mercy Clinic - Cancer & Hematology
🇺🇸Springfield, Missouri, United States
San Juan Oncology Associates
🇺🇸Farmington, New Mexico, United States
Englewood Hospital and Medical Center
🇺🇸Englewood, New Jersey, United States
Basset Medical Center
🇺🇸Cooperstown, New York, United States
Clinical Research Alliance
🇺🇸Lake Success, New York, United States
Hematology Oncology Associates of Central New York
🇺🇸East Syracuse, New York, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Saint Francis Cancer Center
🇺🇸Greenville, South Carolina, United States
GHS Cancer Institute
🇺🇸Greenville, South Carolina, United States
Oncology and Hematology Associates of Southwest Virginia
🇺🇸Roanoke, Virginia, United States
HSHS St. Vincent Hospital Regional Cancer Center
🇺🇸Green Bay, Wisconsin, United States
West Virginia University Mary Babb Randolph Cancer Center (MBRCC)
🇺🇸Morgantown, West Virginia, United States
Border Medical Oncology
🇦🇺East Albury, Australia
Landeskrankenhaus Feldkirch
🇦🇹Rankweil, Austria
Centre Hospitalier de St. Mary
🇨🇦Pointe-Claire, Quebec, Canada
CHU de Liege
🇧🇪Liège, Belgium
The Atlantic Clinical Cancer Research Unit (ACCRU)
🇨🇦Halifax, Nova Scotia, Canada
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, China
Chinese PLA General Hospital
🇨🇳Beijing, China
The Second Affiliated Hospital Zhejiang University
🇨🇳Hangzhou, China
Jiangsu Cancer Hospital
🇨🇳Nanjing, China
Tianjin Medical University Cancer Institute & Hospital
🇨🇳Tianjin, China
The First Affiliated Hospital of Xian Jiao Tong University
🇨🇳Xian, China
Hôpital Trousseau, CHRU de Tours
🇫🇷Chambray-lès-Tours, France
IRCCS Azienda Ospedaliera S.Maria Nuova
🇮🇹Reggio Emilia, Italy
Isala Ziekenhuis
🇳🇱Zwolle, Netherlands
Shizuoka Cancer Center
🇯🇵Shizuoka, Japan
Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Centrum Onkologii Ziemi Lubelskiej
🇵🇱Lublin, Poland
Privolzhsk District Medical Center
🇷🇺Nizhny Novgorod, Russian Federation
Republic Clinical Oncology Dispensary
🇷🇺Kazan, Russian Federation
Budgetary Healthcare Institution of Omsk Region
🇷🇺Omsk, Russian Federation
Orenburg Regional Clinical Oncology Dispensary
🇷🇺Orenburg, Russian Federation
Pyatigorsk Oncology Dispensary
🇷🇺Pyatigorsk, Russian Federation
FSBI "Russian Research Centre of Radiology and Surgical Technologies"
🇷🇺Saint Petersburg, Russian Federation
Multi-type clinic 'REAVIZ'
🇷🇺Samara, Russian Federation
St.Petersburg Medical Universitet n.a. I.P. Pavlov
🇷🇺Saint Petersburg, Russian Federation
City Clinical Oncology Dispensary
🇷🇺Saint Petersburg, Russian Federation
National Research Mordovia State University
🇷🇺Saransk, Russian Federation
Hospital Vall d´Hebron
🇪🇸Barcelona, Spain
National Cancer Centre Singapore
🇸🇬Singapore, Singapore
Hospital Universitario Gregorio Marañón
🇪🇸Madrid, Spain
(ICO) Hospital Duran i Reynals
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
Hospital Universitario Puerta de Hierro
🇪🇸Madrid, Spain
Hospital Regional Universitario de Málaga
🇪🇸Málaga, Spain
Hospital Universitario Fundacion Alcorcon
🇪🇸Madrid, Spain
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung City, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
LinKou Chang Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei City, Taiwan
UC Davis
🇺🇸Sacramento, California, United States
Wake Forest Baptist Hospital
🇺🇸Winston-Salem, North Carolina, United States
UF Health Cancer Center - Orlando Health
🇺🇸Orlando, Florida, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Virginia Cancer Institute
🇺🇸Richmond, Virginia, United States
The Cancer Institute Hospital Of JFCR
🇯🇵Koto-Ku, Tokyo, Japan
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdańsk, Poland
Centro Hospitalar do Porto, E.P.E
🇵🇹Porto, Portugal
IPO Porto Francisco Gentil, E.P.E.
🇵🇹Porto, Portugal
Kyorin University Hopsital
🇯🇵Mitaka, Tokyo, Japan
Fundação Champalimaud
🇵🇹Lisboa, Portugal
Saint Luke's Hospital
🇺🇸Kansas City, Missouri, United States
HCA Midwest Division (Kansas City)
🇺🇸Kansas City, Missouri, United States
UNC Chapel Hill / Lineberger Comprehensive Cancer
🇺🇸Chapel Hill, North Carolina, United States
Charleston Hematology Oncology Associates
🇺🇸Charleston, South Carolina, United States
Medical University of South Carolina (MUSC)
🇺🇸Charleston, South Carolina, United States
Ciusssmcq
🇨🇦Trois-Rivières, Quebec, Canada
University Medical Center Utrecht
🇳🇱Utrecht, Netherlands
The 81 Hospital of the Chinese Peoples Liberation Army
🇨🇳Nanjing, China