A Study of Napabucasin (BBI-608) in Combination With FOLFIRI in Adult Patients With Previously Treated Metastatic Colorectal Cancer
- Conditions
- Colorectal Cancer
- Interventions
- Registration Number
- NCT02753127
- Lead Sponsor
- Sumitomo Pharma America, Inc.
- Brief Summary
This is an international multi-center, prospective, open-label, randomized, adaptive design phase 3 trial of the cancer stem cell pathway inhibitor napabucasin plus standard bi-weekly FOLFIRI versus standard bi-weekly FOLFIRI in patients with previously treated metastatic colorectal cancer (CRC).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1253
- Written, signed consent for trial participation must be obtained from the patient appropriately in accordance with applicable ICH guidelines and local and regulatory requirements prior to the performance of any study specific procedure.
- Must have histologically confirmed advanced CRC that is metastatic.
- Must have failed treatment with one regimen containing a fluoropyrimidine, oxaliplatin with or without bevacizumab for metastatic disease. All patients must have received a minimum of 6 weeks of the first-line regimen that included bevacizumab (if applicable), oxaliplatin and a fluoropyrimidine in the same cycle. Treatment failure is defined as radiologic progression during or < 6 months after the last dose of first-line therapy.
- FOLFIRI therapy is appropriate for the patient and is recommended by the Investigator.
- Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as necessary to document all sites of disease performed within 21 days prior to randomization. Patients with either measurable disease or non-measurable evaluable disease are eligible.
- Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Must be ≥ 18 years of age.
- For male or female patient of child bearing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 180 days for female and male patients, of the final FOLFIRI dose. Patients who receive single agent napabucasin without FOLFIRI must agree to use contraception or take measures to avoid pregnancy during the study and for 30 days for female patients and 90 days for male patients, of the final napabucasin dose.
- Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 5 days prior to randomization. The minimum sensitivity of the pregnancy test must be 25 IU/L or equivalent units of HCG.
- Must have alanine transaminase (ALT) ≤ 3 × institutional upper limit of normal (ULN) [≤ 5 × ULN in presence of liver metastases] within 14 days prior to randomization.
- Must have hemoglobin (Hgb) ≥ 9.0 g/dL within 14 days prior to randomization. Must not have required transfusion of red blood cells within 1 week of baseline Hgb assessment.
- Must have total bilirubin ≤ 1.5 × institutional ULN [≤ 2.0 x ULN in presence of liver metastases] within 14 days prior to randomization.
- Must have creatinine ≤ 1.5 × institutional ULN or Creatinine Clearance > 50 ml/min (as calculated by the Cockcroft-Gault equation (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) within 14 days prior to randomization.
- Must have absolute neutrophil count ≥ 1.5 x 10^9/L within 14 days prior to randomization.
- Must have platelet count ≥ 100 x 10^9/L within 14 days prior to randomization. Must not have required transfusion of platelets within 1 week of baseline platelet assessment.
- 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.
- Other baseline laboratory evaluations, listed in Section 6.0, must be done within 14 days prior to randomization.
- Patient 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 biomarker assays may be conducted. Submission of the tissue is to occur prior to randomization, unless approved by the Sponsor. Where local center regulations prohibit submission of blocks of tumor tissue, two 2 mm cores of tumor from the block and 10-30 unstained slides of whole sections of representative tumor tissue are preferred. Where two 2 mm cores of tumor from the block are unavailable, 10-30 unstained slides of whole sections of representative tumor tissue alone are 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.
- Patient must consent to provision of a sample of blood in order that the specific correlative marker assays may be conducted.
- 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.
- Protocol treatment is to begin within 2 calendar days of patient randomization.
- 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.
-
Anti-cancer chemotherapy or biologic therapy if administered prior to the first planned dose of study medication (napabucasin or FOLFIRI) within period of time equivalent to the usual cycle length of the regimen. An exception is made for oral fluoropyrimidines (e.g. capecitabine, S-1), where a minimum of 10 days since last dose must be observed prior to the first planned dose of study medication. Standard dose of bevacizumab (5 mg/kg) may be administered prior to FOLFIRI infusion, per Investigator decision, for as long as permanent decision to include or exclude bevacizumab is made prior to patient randomization. Radiotherapy, immunotherapy (including immunotherapy administered for non-malignant diseaseneoplastic treatment purposes), or investigational agents within four weeks of first planned dose of study medication, with the exception of a single dose of radiation up to 8 Gy (equal to 800 RAD) with palliative intent for pain control up to 14 days before randomization.
-
More than one prior chemotherapy regimen administered in the metastatic setting.
-
Major surgery within 4 weeks prior to randomization.
-
Patients with any known brain or leptomeningeal metastases are excluded, even if treated.
-
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 FOLFIRI and for 180 days after the last dose of FOLFIRI.
-
Gastrointestinal disorder(s) which, in the opinion of the Qualified/Principal Investigator, would significantly impede the absorption of an oral agent (e.g. intestinal occlusion, active Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection).
-
Unable or unwilling to swallow napabucasin capsules daily.
-
Prior treatment with napabucasin.
-
Uncontrolled intercurrent 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.
-
Known hypersensitivity to 5-fluorouracil/leucovorin
-
Known dihydropyrimidine dehydrogenase (DPD) deficiency
-
Known hypersensitivity to irinotecan
-
Chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis)
-
Patients receiving treatment with St. John's wort or Phenytoin.
-
Patients who plan to receive yellow fever vaccine during the course of the study treatment.
-
Abnormal glucuronidation of bilirubin, known Gilbert's syndrome
-
Patients with QTc interval > 470 milliseconds
-
For patients to be treated with a regimen containing bevacizumab:
- History of cardiac disease: congestive heart failure (CHF) > New York Heart Association (NYHA) Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; 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.
- History of arterial thrombotic or embolic events (within 6 months prior to study entry)
- Significant vascular disease (e.g., aortic aneurysm, aortic dissection, symptomatic peripheral vascular disease)
- 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 study enrollment
- Proteinuria at screening as demonstrated by urinalysis with proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
- History of abdominal fistula, gastrointestinal perforation, peptic ulcer, or intra-abdominal abscess within 6 months
- Ongoing serious, non-healing wound, ulcer, or bone fracture
- Known hypersensitivity to any component of bevacizumab
- History of reversible posterior leukoencephalopathy syndrome (RPLS)
- History of hypersensitivity to Chinese hamster ovary (CHO) cells or other human or humanized recombinant antibodies.
-
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 with no evidence of disease for > 3 years.
-
Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.
-
Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Napabucasin plus FOLFIRI Fluorouracil Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will start at least 2 hours following the first daily dose of napabucasin and will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion or at least 2 hours following the first daily dose of napabucasin if bevacizumab is not administered. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle. Napabucasin plus FOLFIRI Leucovorin Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will start at least 2 hours following the first daily dose of napabucasin and will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion or at least 2 hours following the first daily dose of napabucasin if bevacizumab is not administered. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle. Napabucasin plus FOLFIRI Bevacizumab Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will start at least 2 hours following the first daily dose of napabucasin and will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion or at least 2 hours following the first daily dose of napabucasin if bevacizumab is not administered. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle. Napabucasin plus FOLFIRI Irinotecan Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will start at least 2 hours following the first daily dose of napabucasin and will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion or at least 2 hours following the first daily dose of napabucasin if bevacizumab is not administered. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle. FOLFIRI Fluorouracil Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle. FOLFIRI Leucovorin Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle. FOLFIRI Irinotecan Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle. FOLFIRI Bevacizumab Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle. Napabucasin plus FOLFIRI Napabucasin Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will start at least 2 hours following the first daily dose of napabucasin and will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion or at least 2 hours following the first daily dose of napabucasin if bevacizumab is not administered. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Randomization to Date of Death from any cause or database cutoff date (28 Apr 2020) (Approximately 43 months) Overall survival was defined as the time from randomization until death from any cause.
Patients who are alive at the time of the interim or the final analyses or who have become lost to follow-up will be censored on the date the patient was last known to be alive.
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Randomization to Date of Death or until the date of first documented objective disease progression or database cutoff date (28 Apr 2020) (Approximately 43 months) PFS is defined as the time from randomization to the first objective documentation of disease progression per RECIST 1.1 (PD) or death, whichever comes first.
Mean Change From Baseline for Global Health Status at Time 2 (Cycle 5 Day 1) and Time 4 (Cycle 9 Day 1). From baseline at Time 2 (Cycle 5 Day 1), approximately 57 days and Time 4 (Cycle 9 Day 1), approximately 113 days The Quality of Life (QoL) of patients will be assessed using European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ-C30) (EORTC QLQ-30) while the patient remains on study treatment (FOLFIRI with or without BBI-608). EORTC QLQ-30 is used to assess the overall quality of life in cancer patients using 28 questions with a 4 point scale. (1 'Not at all' to 4'Very Much'); 2 questions use a 7-point sale (1 'Very Poor' to 7 'Excellent'). Scores are averaged and transformed to 0-100 scale; higher overall score = better quality of life.
Disease Control Rate (DCR) Randomization to Date of Death or until the date of first documented objective disease progression or database cutoff date (28 Apr 2020) (Approximately 43 months) DCR is defined as the percentage of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1. The primary estimate of DCR will be based on patients with measurable disease by RECIST 1.1 at randomization
Objective Response Rate (ORR) Randomization to Date of Death or until the date of first documented objective disease progression or database cutoff date (28 Apr 2020) (Approximately 43 months) ORR is defined as the proportion of patients with a documented complete response and partial response (CR + PR) based on RECIST 1.1. The primary estimate for ORR will be based on patients with measurable disease by RECIST 1.1 at randomization.
Mean Change From Baseline for Physical Functioning Status at Time 2 (Cycle 5 Day 1) and Time 4 (Cycle 9 Day 1). From baseline at Time 2 (Cycle 5 Day 1) and Time 4 (Cycle 9 Day 1) The Quality of Life (QoL) of patients will be assessed using European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ-C30) (EORTC QLQ-30) while the patient remains on study treatment (FOLFIRI with or without BBI-608). EORTC QLQ-30 is used to assess the overall quality of life in cancer patients using 28 questions with a 4 point scale. (1 'Not at all' to 4'Very Much'); 2 questions use a 7-point sale (1 'Very Poor' to 7 'Excellent'). Scores are averaged and transformed to 0-100 scale; higher overall score = better quality of life.
Number of Patients With Adverse Events in the General Population All adverse event are collected from date of signed informed consent until 30 days after protocol treatment discontinuation. Outcome followed until study discontinuation up to 4 years All patients who have received at least one dose of either BBI-608 or FOLFIRI 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.
Trial Locations
- Locations (207)
Illinois Cancer Specialists
🇺🇸Arlington Heights, Illinois, United States
Dana Farber
🇺🇸Boston, Massachusetts, United States
University of Toronto - Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Saint Michael's Hospital Li Ka Shing Knowledge Institute
🇨🇦Toronto, Ontario, Canada
National University Cancer Institute
🇸🇬Singapore, Central Singapore, Singapore
Raffles Hospital
🇸🇬Singapore, Central Singapore, Singapore
Soroka University Medical Center
🇮🇱Be'er Sheva, Israel
Tel Aviv Sourasky Medical Center - Oncology
🇮🇱Tel-Aviv, Israel
National Hospital Organization Osaka National Hospital
🇯🇵Osaka, Japan
Meir Medical Center
🇮🇱Kefar Saba, Israel
The cancer insitute hospital of JFCR (Japanese Foundation For Cancer Research)
🇯🇵Koto-ku, Tokyo, Japan
Centre Eugene Marquis
🇫🇷Rennes, France
Saitama Cancer Center
🇯🇵Kita-Adachi, Saitama, Japan
Minnesota Oncology Hematology, P.A.
🇺🇸Minneapolis, Minnesota, United States
The Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Millenium Oncology
🇺🇸Houston, Texas, United States
Virginia Mason
🇺🇸Seattle, Washington, United States
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
Ha'Emek Medical Center
🇮🇱Afula, Israel
Palm Beach Cancer Institute
🇺🇸West Palm Beach, Florida, United States
Alabama Oncology
🇺🇸Birmingham, Alabama, United States
Baptist Health Medical Group Oncology, LLC
🇺🇸Miami, Florida, United States
Memorial Cancer Institute at Memorial Hospital
🇺🇸Hollywood, Florida, United States
Comprehensive Blood and Cancer Center
🇺🇸Bakersfield, California, United States
Emory University/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
City of Hope- Comprehensive Care Center
🇺🇸Duarte, California, United States
St Mary's Hospital & Regional Med Center
🇺🇸Grand Junction, Colorado, United States
Healthcare Research Network III, LLC
🇺🇸Tinley Park, Illinois, United States
Saint Francis Cancer Treatment Center
🇺🇸Grand Island, Nebraska, United States
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
UCLA Hematology Oncology Santa Monica
🇺🇸Santa Monica, California, United States
Florida Cancer Specialists & Research Institute Fort Myers
🇺🇸Fort Myers, Florida, United States
Piedmont Cancer Institute, PC
🇺🇸Atlanta, Georgia, United States
Cancer Center of Kansas
🇺🇸Wichita, Kansas, United States
Parkview Research Center
🇺🇸Fort Wayne, Indiana, United States
Texas Oncology - Wichita Falls Texoma Cancer Center
🇺🇸Wichita Falls, Texas, United States
Northern Utah Associates
🇺🇸Ogden, Utah, United States
Texas Oncology - Tyler
🇺🇸Tyler, Texas, United States
Bankstown-Lidcombe Hospital
🇦🇺Bankstown, New South Wales, Australia
Southeastern Medical Oncology Center
🇺🇸Goldsboro, North Carolina, United States
Texas Oncology - Denton South
🇺🇸Denton, Texas, United States
Texas Health Physicians Group
🇺🇸Plano, Texas, United States
Fort Belvoir Community Hospital
🇺🇸Fort Belvoir, Virginia, United States
Virginia Oncology Associates
🇺🇸Hampton, Virginia, United States
Texas Oncology - Fort Worth
🇺🇸Fort Worth, Texas, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Port Macquaries Base Hospital
🇦🇺Port Macquarie, New South Wales, Australia
Northwest Cancer Specialists, P.C.
🇺🇸Vancouver, Washington, United States
St Vincent's hospital Melbourne
🇦🇺Fitzroy, New South Wales, Australia
Henan Cancer Hospital
🇨🇳Henan, China
Jiangsu Province Hospital
🇨🇳Jiangsu, China
FN Hradec Kralove
🇨🇿Hradec Králové, Královéhradecký Kraj, Czechia
Vseobecna fakultni nemocnice v Praze
🇨🇿Prague, Czechia
Sunshine Coast Hospital and Health Service
🇦🇺Nambour, Queensland, Australia
Gold Coast University Hosptial
🇦🇺Southport, Queensland, Australia
Grand Hôpital de Charleroi - Site Notre-Dame
🇧🇪Charleroi, Hainaut, Belgium
AZ Sint-Lucas - Campus Sint-Lucas
🇧🇪Brugge, West-Vlaanderen, Belgium
St Vincent's Hospital
🇦🇺Darlinghurst, New South Wales, Australia
Flinders Medical Centre
🇦🇺Bedford Park, South Australia, Australia
The Queen Elizabeth Hospital
🇦🇺Woodville, South Australia, Australia
CHU de Liège - Domaine Universitaire du Sart Tilman
🇧🇪Bruxelles, Liège, Belgium
Centre Paul Papin
🇫🇷Angers, France
Masarykuv onkologicky ustav
🇨🇿Brno, Czechia
Prince of Wales Hospital
🇦🇺Randwick, Australia
Beijing Cancer Hospital
🇨🇳Beijing, China
Hopital Notre-Dame du CHUM
🇨🇦Montréal, Quebec, Canada
Hospitalier Jean Minjoz
🇫🇷Besançon, France
Centre de Lutte Contre le Cancer (CLCC)
🇫🇷Dijon, France
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
AZ Turnhout - Campus Sint-Elisabeth
🇧🇪Turnhout, Antwerpen, Belgium
AZ Sint-Jan Brugge - Oostende - Campus Sint-Jan
🇧🇪Brugge, West-Vlaanderen, Belgium
CHU Estaing
🇫🇷Clermont Ferrand, France
St. Mary's Hospital Center
🇨🇦Montréal, Quebec, Canada
Charité Universitätsmedizin
🇩🇪Berlin, Germany
Schwerpunkpraxis für Hämatologie und Onkologie
🇩🇪Magdeburg, Sachsen-Anhalt, Germany
Gesundheitszentrum Wetterau
🇩🇪Bad Nauheim, Germany
CHU de Nantes - Hopital Hotel Dieu
🇫🇷Nantes, France
Hôpital Privé des Côtes d'Armor - Service oncologie
🇫🇷Plérin, France
Rabin MC - Oncology, Davidoff Center
🇮🇱Petah tikva, Israel
Ziv Medical Center (The Rebecca Sieff Hospital)
🇮🇱Safed, Israel
AO S. Martino, IRCCS, IST
🇮🇹Genova, Italy
The Barzilai Medical Center - Oncology Institute
🇮🇱Ashkelon, Israel
Medizinische Universitaetsklin
🇩🇪Ulm, Germany
Irccs Irst
🇮🇹Meldola, Forli, Italy
Policlinico S.Orsola Malpighi, AOU di Bologna
🇮🇹Bologna, Italy
Ospedale Guglielmo da Saliceto, AUSL Piacenza
🇮🇹Piacenza, Italy
Ieo, Irccs
🇮🇹Milano, Italy
AOU Ospedali Riuniti Umberto I - GM.Lanc
🇮🇹Torrette Di Ancona, Ancona, Italy
PO di Cremona, ASST di Cremona
🇮🇹Cremona, Italy
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan
AOU Città della Salute e della Scienza di Torino - Molinette
🇮🇹Torino, Italy
Medisch Centrum Leeuwarden
🇳🇱Leeuwarden, Friesland, Netherlands
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Aichi Cancer Center Hospital
🇯🇵Nagoya, Aichi, Japan
Hospital Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain
H.C.U.Valencia
🇪🇸Valencia, Spain
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Osaka Medical College Hospital
🇯🇵Takatsuki, Osaka, Japan
Medical Hospital, Tokyo Medical and Dental University
🇯🇵Bunkyo-ku, Tokyo, Japan
Academisch Medisch Centrum
🇳🇱Amsterdam, Netherlands
Spaarne Gasthuis
🇳🇱Hoofddorp, Netherlands
Samsung Medical Center
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Elizabeth Tweesteden Ziekenhuis locatie Tilburg
🇳🇱Tilburg, Netherlands
Consorci Hospital General Universitari Valencia (CHGUV)
🇪🇸Comunidad Valenciana, Valencia, Spain
Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Asturias, Spain
H.U.V. del Rocío
🇪🇸Sevilla, Andalucía, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Son Llatzer
🇪🇸Baleares, Spain
Hospital Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Universitario Vall d'Hebrón
🇪🇸Barcelona, Spain
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
The Ottawa Hospital Cancer Centre
🇨🇦Ottawa, Ontario, Canada
Korea University Guro Hospital
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Leopoldina Krankenhaus Med. Klinik 2
🇩🇪Schweinfurt, Bayern, Germany
Universitätsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Sachsen, Germany
Charite - Campus Benjamin Franklin (Cbf)
🇩🇪Berlin, Germany
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Macarena
🇪🇸Sevilla, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Northern Cancer Institute
🇦🇺St Leonards, New South Wales, Australia
Sarah Cannon Research Institution
🇺🇸Saint Petersburg, Florida, United States
Northshore University Healthsystem
🇺🇸Evanston, Illinois, United States
Suburban Hematology-Oncology Associates, PC - Lawrenceville
🇺🇸Lawrenceville, Georgia, United States
Northwestern Medicine Cancer Center
🇺🇸Warrenville, Illinois, United States
Umass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Indiana University Health Goshen Center for Cancer Care
🇺🇸Goshen, Indiana, United States
Michiana Hematology Oncology, PC
🇺🇸Mishawaka, Indiana, United States
Texas Oncology - Dallas Center
🇺🇸Dallas, Texas, United States
Blue Ridge Cancer Care
🇺🇸Roanoke, Virginia, United States
MVZ Onkologischer Schwerpunkt am Oskar-Helene-Heim
🇩🇪Berlin, Germany
US Oncology - Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Mayo Clinic Arizona
🇺🇸Rochester, Minnesota, United States
University of Michigan Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Cancer Research Network of Nebraska / Oncology Associates PC
🇺🇸Omaha, Nebraska, United States
Missouri Valley Cancer Consortium
🇺🇸Omaha, Nebraska, United States
Tennessee Oncology PLLC
🇺🇸Omaha, Nebraska, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Arizona Oncology Associates, PC - HOPE
🇺🇸Tucson, Arizona, United States
Los Angeles Hematology Oncology Medical Group
🇺🇸Los Angeles, California, United States
University of California-San Diego/Moores UCSD Cancer Center
🇺🇸La Jolla, California, United States
Medical Oncology Hematology Consultants, PA
🇺🇸Newark, Delaware, United States
St. Joseph Heritage Healthcare
🇺🇸Santa Rosa, California, United States
Missouri Baptist Medical Center ACCRU Network Site
🇺🇸Saint Louis, Missouri, United States
Darthmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Carol G. Simon Cancer Center
🇺🇸Morristown, New Jersey, United States
North Shore Hematology Oncology Associates
🇺🇸East Setauket, New York, United States
University of New Mexico
🇺🇸Albuquerque, New Mexico, United States
Roswell Park Cancer Center
🇺🇸Buffalo, New York, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
VA Pittsburgh Healthcare System
🇺🇸Pittsburgh, Pennsylvania, United States
Toledo Clinic Cancer Centers
🇺🇸Toledo, Ohio, United States
Sanford Cancer Center
🇺🇸Sioux Falls, South Dakota, United States
West Cancer Center
🇺🇸Memphis, Tennessee, United States
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States
Texas Oncology-San Antonio
🇺🇸San Antonio, Texas, United States
Peninsula & South Eastern Haematology and Oncology Group
🇦🇺Frankston, Victoria, Australia
Goulburn Valley Health
🇦🇺Shepparton, Victoria, Australia
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Hôpital Morvan - CHRU de Brest - cancérologie et d'hématolog
🇫🇷Brest, France
Hospital of Poitiers
🇫🇷Poitiers, France
Hôpital Européen Georges Pompidou - Digestive Oncology
🇫🇷Paris, France
Centre Rene Gauducheau
🇫🇷Saint-Herblain, France
DRK Kliniken Berlin Koepenick
🇩🇪Berlin, Germany
Vivantes Klinikum Am Urban
🇩🇪Berlin, Germany
Universitätsklinikum Marburg
🇩🇪Marburg, Germany
Asklepios Klinik Altona
🇩🇪Hamburg, Germany
Ospedale Santa Maria del Prato
🇮🇹Feltre, Belluno, Italy
Università degli studi della Campania "L.Vanvitelli"
🇮🇹Napoli, Italy
AOU Policlinico di Modena
🇮🇹Modena, Italy
Shizuoka Cancer Center
🇯🇵Sunto, Shizuoka, Japan
National Kyushu Cancer Center
🇯🇵Fukuoka, Japan
Osaka Medical Center for Cancer and Cardiovascular Diseases
🇯🇵Osaka, Japan
Yeungnam University Medical Center
🇰🇷Daegu, Daegu Gwang'yeogsi, Korea, Republic of
Ajou University Hospital
🇰🇷Suwon, Gyeonggido, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Incheon Gwang'yeogsi, Korea, Republic of
National Cancer Centre
🇸🇬Singapore, Central Singapore, Singapore
Korea University Anam Hospital
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Maastricht UMC
🇳🇱Maastricht, Netherlands
Hospital General Universitario de Elche
🇪🇸Elche, Alicante, Spain
Complexo Hospital Universitario A Coruña
🇪🇸A Coruña, Galicia, Spain
Hospital Universitario Fundacion Alcorcon (HUFA)
🇪🇸Alcorcón, Madrid, Spain
Hospital Universitario Puerta de Hierro-Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Research Medical Center
🇺🇸Kansas City, Missouri, United States
Texas Oncology-Austin Midtown
🇺🇸Austin, Texas, United States
Imelda Ziekenhuis
🇧🇪Bonheiden, Antwerpen, Belgium
Hôpital Erasme
🇧🇪Bruxelles, Brussels Capital Region, Belgium
UZ Leuven - Campus Gasthuisberg
🇧🇪Leuven, Vlaams Brabant, Belgium
Bendigo Hospital
🇦🇺Bendigo, Victoria, Australia
The Chaim Sheba Medical Centre - Division of Oncology
🇮🇱Tel HaShomer, Israel
Shaare Zedek Medical center
🇮🇱Jerusalem, Israel
National Hospital Organization Shikoku Cancer Center
🇯🇵Matsunami, Ehime, Japan
Hokkaido University Hospital
🇯🇵Sapporo, Hokkaido, Japan
Kobe City Medical Center General Hospital
🇯🇵Kobe, Hyogo, Japan
ST. Marianna University School of Medicine
🇯🇵Kawasaki, Kanagawa, Japan
Osaka University Hospital
🇯🇵Suita, Osaka, Japan
AUSL della Romagna, Osp. degli Infermi
🇮🇹Faenza, Ravenna, Italy
Western Health
🇦🇺Melbourne, Victoria, Australia
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
Facharztzentrum Eppendorf
🇩🇪Hamburg, Germany
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Pamela Youde Nethersole Eastern Hospital
🇭🇰Hong Kong, Hong Kong