Clinical trial NCT02753127: A Study of Napabucasin (BBI-608) in Combination With FOLFIRI in Adult Patients With Previously Treated Metastatic Colorectal Cancer
Official title: A Phase 3 Study of BBI-608 in Combination With 5-Fluorouracil, Leucovorin, Irinotecan (FOLFIRI) in Adult Patients With Previously Treated Metastatic Colorectal Cancer (CRC).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Rectal Diseases
Lead sponsor: Sumitomo Pharma America, Inc.
Sponsor class: INDUSTRY
First posted: 2016-04-27
Enrollment: 1253
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

1. 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.
2. Must have histologically confirmed advanced CRC that is metastatic.
3. 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.
4. FOLFIRI therapy is appropriate for the patient and is recommended by the Investigator.
5. 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.
6. Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
7. Must be ≥ 18 years of age.
8. 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.
9. 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.
10. 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.
11. 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.
12. Must have total bilirubin ≤ 1.5 × institutional ULN \[≤ 2.0 x ULN in presence of liver metastases\] within 14 days prior to randomization.
13. 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.
14. Must have absolute neutrophil count ≥ 1.5 x 10\^9/L within 14 days prior to randomization.
15. 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.
16. 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.
17. Other baseline laboratory evaluations, listed in Section 6.0, must be done within 14 days prior to randomization.
18. 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.
19. Patient must consent to provision of a sample of blood in order that the specific correlative marker assays may be conducted.
20. 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.
21. Protocol treatment is to begin within 2 calendar days of patient randomization.
22. 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.

Exclusion Criteria:

1. 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.
2. More than one prior chemotherapy regimen administered in the metastatic setting.
3. Major surgery within 4 weeks prior to randomization.
4. Patients with any known brain or leptomeningeal metastases are excluded, even if treated.
5. 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.
6. 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).
7. Unable or unwilling to swallow napabucasin capsules daily.
8. Prior treatment with napabucasin.
9. 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.
10. Known hypersensitivity to 5-fluorouracil/leucovorin
11. Known dihydropyrimidine dehydrogenase (DPD) deficiency
12. Known hypersensitivity to irinotecan
13. Chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis)
14. Patients receiving treatment with St. John's wort or Phenytoin.
15. Patients who plan to receive yellow fever vaccine during the course of the study treatment.
16. Abnormal glucuronidation of bilirubin, known Gilbert's syndrome
17. Patients with QTc interval \> 470 milliseconds
18. 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.
19. 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.
20. Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.
21. Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Randomization to Date of Death from any cause or database cutoff date (28 Apr 2020) (Approximately 43 months)
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 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)
measure: Disease Control Rate (DCR)
timeFrame: 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)
measure: Objective Response Rate (ORR)
timeFrame: 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)
measure: Mean Change From Baseline for Global Health Status at Time 2 (Cycle 5 Day 1) and Time 4 (Cycle 9 Day 1).
timeFrame: From baseline at Time 2 (Cycle 5 Day 1), approximately 57 days and Time 4 (Cycle 9 Day 1), approximately 113 days
measure: Mean Change From Baseline for Physical Functioning Status at Time 2 (Cycle 5 Day 1) and Time 4 (Cycle 9 Day 1).
timeFrame: From baseline at Time 2 (Cycle 5 Day 1) and Time 4 (Cycle 9 Day 1)
measure: Number of Patients With Adverse Events in the General Population
timeFrame: 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
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Oncology
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE
state: Arizona
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Duarte
country: United States
facility: City of Hope- Comprehensive Care Center
state: California
city: La Jolla
country: United States
facility: University of California-San Diego/Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: Los Angeles Hematology Oncology Medical Group
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology Oncology Santa Monica
state: California
city: Santa Rosa
country: United States
facility: St. Joseph Heritage Healthcare
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Grand Junction
country: United States
facility: St Mary's Hospital & Regional Med Center
state: Colorado
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants, PA
state: Delaware
city: Fort Myers
country: United States
facility: Florida Cancer Specialists & Research Institute Fort Myers
state: Florida
city: Hollywood
country: United States
facility: Memorial Cancer Institute at Memorial Hospital
state: Florida
city: Miami
country: United States
facility: Baptist Health Medical Group Oncology, LLC
state: Florida
city: Saint Petersburg
country: United States
facility: Sarah Cannon Research Institution
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Cancer Institute
state: Florida
city: Atlanta
country: United States
facility: Piedmont Cancer Institute, PC
state: Georgia
city: Atlanta
country: United States
facility: Emory University/Winship Cancer Institute
state: Georgia
city: Lawrenceville
country: United States
facility: Suburban Hematology-Oncology Associates, PC - Lawrenceville
state: Georgia
city: Arlington Heights
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Evanston
country: United States
facility: Northshore University Healthsystem
state: Illinois
city: Tinley Park
country: United States
facility: Healthcare Research Network III, LLC
state: Illinois
city: Warrenville
country: United States
facility: Northwestern Medicine Cancer Center
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Research Center
state: Indiana
city: Goshen
country: United States
facility: Indiana University Health Goshen Center for Cancer Care
state: Indiana
city: Mishawaka
country: United States
facility: Michiana Hematology Oncology, PC
state: Indiana
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Boston
country: United States
facility: Dana Farber
state: Massachusetts
city: Worcester
country: United States
facility: Umass Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Arizona
state: Minnesota
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center ACCRU Network Site
state: Missouri
city: Grand Island
country: United States
facility: Saint Francis Cancer Treatment Center
state: Nebraska
city: Omaha
country: United States
facility: Missouri Valley Cancer Consortium
state: Nebraska
city: Omaha
country: United States
facility: Cancer Research Network of Nebraska / Oncology Associates PC
state: Nebraska
city: Omaha
country: United States
facility: Tennessee Oncology PLLC
state: Nebraska
city: Lebanon
country: United States
facility: Darthmouth-Hitchcock Medical Center
state: New Hampshire
city: Morristown
country: United States
facility: Carol G. Simon Cancer Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Center
state: New York
city: East Setauket
country: United States
facility: North Shore Hematology Oncology Associates
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Goldsboro
country: United States
facility: Southeastern Medical Oncology Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Toledo
country: United States
facility: Toledo Clinic Cancer Centers
state: Ohio
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: VA Pittsburgh Healthcare System
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford Cancer Center
state: South Dakota
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Memphis
country: United States
facility: West Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology-Austin Midtown
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Dallas Center
state: Texas
city: Denton
country: United States
facility: Texas Oncology - Denton South
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology - Fort Worth
state: Texas
city: Houston
country: United States
facility: Millenium Oncology
state: Texas
city: Plano
country: United States
facility: Texas Health Physicians Group
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology-San Antonio
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Wichita Falls
country: United States
facility: Texas Oncology - Wichita Falls Texoma Cancer Center
state: Texas
city: Ogden
country: United States
facility: Northern Utah Associates
state: Utah
city: Fairfax
country: United States
facility: US Oncology - Virginia Cancer Specialists, PC
state: Virginia
city: Fort Belvoir
country: United States
facility: Fort Belvoir Community Hospital
state: Virginia
city: Hampton
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Roanoke
country: United States
facility: Blue Ridge Cancer Care
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Washington
city: Bankstown
country: Australia
facility: Bankstown-Lidcombe Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital
state: New South Wales
city: Fitzroy
country: Australia
facility: St Vincent's hospital Melbourne
state: New South Wales
city: Port Macquarie
country: Australia
facility: Port Macquaries Base Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: Northern Cancer Institute
state: New South Wales
city: Nambour
country: Australia
facility: Sunshine Coast Hospital and Health Service
state: Queensland
city: Southport
country: Australia
facility: Gold Coast University Hosptial
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Bendigo
country: Australia
facility: Bendigo Hospital
state: Victoria
city: Frankston
country: Australia
facility: Peninsula & South Eastern Haematology and Oncology Group
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Western Health
state: Victoria
city: Shepparton
country: Australia
facility: Goulburn Valley Health
state: Victoria
city: Randwick
country: Australia
facility: Prince of Wales Hospital
city: Bonheiden
country: Belgium
facility: Imelda Ziekenhuis
state: Antwerpen
city: Bonheiden
country: Belgium
facility: Imelda Ziekenhuis
state: Antwerpen
city: Bonheiden
country: Belgium
facility: Imelda Ziekenhuis
state: Antwerpen
city: Turnhout
country: Belgium
facility: AZ Turnhout - Campus Sint-Elisabeth
state: Antwerpen
city: Bruxelles
country: Belgium
facility: Hôpital Erasme
state: Brussels Capital Region
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi - Site Notre-Dame
state: Hainaut
city: Bruxelles
country: Belgium
facility: CHU de Liège - Domaine Universitaire du Sart Tilman
state: Liège
city: Leuven
country: Belgium
facility: UZ Leuven - Campus Gasthuisberg
state: Vlaams Brabant
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge - Oostende - Campus Sint-Jan
state: West-Vlaanderen
city: Brugge
country: Belgium
facility: AZ Sint-Lucas - Campus Sint-Lucas
state: West-Vlaanderen
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: University of Toronto - Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Saint Michael's Hospital Li Ka Shing Knowledge Institute
state: Ontario
city: Montréal
country: Canada
facility: St. Mary's Hospital Center
state: Quebec
city: Montréal
country: Canada
facility: Hopital Notre-Dame du CHUM
state: Quebec
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Henan
country: China
facility: Henan Cancer Hospital
city: Jiangsu
country: China
facility: Jiangsu Province Hospital
city: Hradec Králové
country: Czechia
facility: FN Hradec Kralove
state: Královéhradecký Kraj
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Brno
country: Czechia
facility: Masarykuv onkologicky ustav
city: Prague
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Angers
country: France
facility: Centre Paul Papin
city: Besançon
country: France
facility: Hospitalier Jean Minjoz
city: Brest
country: France
facility: Hôpital Morvan - CHRU de Brest - cancérologie et d'hématolog
city: Clermont Ferrand
country: France
facility: CHU Estaing
city: Dijon
country: France
facility: Centre de Lutte Contre le Cancer (CLCC)
city: Nantes
country: France
facility: CHU de Nantes - Hopital Hotel Dieu
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou - Digestive Oncology
city: Plérin
country: France
facility: Hôpital Privé des Côtes d'Armor - Service oncologie
city: Poitiers
country: France
facility: Hospital of Poitiers
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Saint-Herblain
country: France
facility: Centre Rene Gauducheau
city: Schweinfurt
country: Germany
facility: Leopoldina Krankenhaus Med. Klinik 2
state: Bayern
city: Magdeburg
country: Germany
facility: Schwerpunkpraxis für Hämatologie und Onkologie
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Dresden
state: Sachsen
city: Bad Nauheim
country: Germany
facility: Gesundheitszentrum Wetterau
city: Berlin
country: Germany
facility: Vivantes Klinikum Am Urban
city: Berlin
country: Germany
facility: Charite - Campus Benjamin Franklin (Cbf)
city: Berlin
country: Germany
facility: DRK Kliniken Berlin Koepenick
city: Berlin
country: Germany
facility: Charité Universitätsmedizin
city: Berlin
country: Germany
facility: MVZ Onkologischer Schwerpunkt am Oskar-Helene-Heim
city: Hamburg
country: Germany
facility: Facharztzentrum Eppendorf
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Marburg
country: Germany
facility: Universitätsklinikum Marburg
city: Ulm
country: Germany
facility: Medizinische Universitaetsklin
city: Hong Kong
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Afula
country: Israel
facility: Ha'Emek Medical Center
city: Ashkelon
country: Israel
facility: The Barzilai Medical Center - Oncology Institute
city: Be'er Sheva
country: Israel
facility: Soroka University Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical center
city: Kefar Saba
country: Israel
facility: Meir Medical Center
city: Petah tikva
country: Israel
facility: Rabin MC - Oncology, Davidoff Center
city: Safed
country: Israel
facility: Ziv Medical Center (The Rebecca Sieff Hospital)
city: Tel HaShomer
country: Israel
facility: The Chaim Sheba Medical Centre - Division of Oncology
city: Tel-Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center - Oncology
city: Torrette Di Ancona
country: Italy
facility: AOU Ospedali Riuniti Umberto I - GM.Lanc
state: Ancona
city: Feltre
country: Italy
facility: Ospedale Santa Maria del Prato
state: Belluno
city: Meldola
country: Italy
facility: Irccs Irst
state: Forli
city: Faenza
country: Italy
facility: AUSL della Romagna, Osp. degli Infermi
state: Ravenna
city: Bologna
country: Italy
facility: Policlinico S.Orsola Malpighi, AOU di Bologna
city: Cremona
country: Italy
facility: PO di Cremona, ASST di Cremona
city: Genova
country: Italy
facility: AO S. Martino, IRCCS, IST
city: Milano
country: Italy
facility: Ieo, Irccs
city: Modena
country: Italy
facility: AOU Policlinico di Modena
city: Napoli
country: Italy
facility: Università degli studi della Campania "L.Vanvitelli"
city: Piacenza
country: Italy
facility: Ospedale Guglielmo da Saliceto, AUSL Piacenza
city: Torino
country: Italy
facility: AOU Città della Salute e della Scienza di Torino - Molinette
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Matsunami
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
state: Ehime
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Kawasaki
country: Japan
facility: ST. Marianna University School of Medicine
state: Kanagawa
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Takatsuki
country: Japan
facility: Osaka Medical College Hospital
state: Osaka
city: Kita-Adachi
country: Japan
facility: Saitama Cancer Center
state: Saitama
city: Sunto
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Bunkyo-ku
country: Japan
facility: Medical Hospital, Tokyo Medical and Dental University
state: Tokyo
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto-ku
country: Japan
facility: The cancer insitute hospital of JFCR (Japanese Foundation For Cancer Research)
state: Tokyo
city: Fukuoka
country: Japan
facility: National Kyushu Cancer Center
city: Osaka
country: Japan
facility: Osaka Medical Center for Cancer and Cardiovascular Diseases
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Medical Center
state: Daegu Gwang'yeogsi
city: Goyang
country: Korea, Republic of
facility: National Cancer Centre
state: Gyeonggido
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
state: Gyeonggido
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
state: Incheon Gwang'yeogsi
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Seoul Teugbyeolsi
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
state: Friesland
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Hoofddorp
country: Netherlands
facility: Spaarne Gasthuis
city: Maastricht
country: Netherlands
facility: Maastricht UMC
city: Tilburg
country: Netherlands
facility: Elizabeth Tweesteden Ziekenhuis locatie Tilburg
city: Singapore
country: Singapore
facility: National University Cancer Institute
state: Central Singapore
city: Singapore
country: Singapore
facility: National Cancer Centre
state: Central Singapore
city: Singapore
country: Singapore
facility: Raffles Hospital
state: Central Singapore
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Sevilla
country: Spain
facility: H.U.V. del Rocío
state: Andalucía
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Badalona
country: Spain
facility: Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: A Coruña
country: Spain
facility: Complexo Hospital Universitario A Coruña
state: Galicia
city: Alcorcón
country: Spain
facility: Hospital Universitario Fundacion Alcorcon (HUFA)
state: Madrid
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro-Majadahonda
state: Madrid
city: Comunidad Valenciana
country: Spain
facility: Consorci Hospital General Universitari Valencia (CHGUV)
state: Valencia
city: Baleares
country: Spain
facility: Hospital Son Llatzer
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebrón
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de la Macarena
city: Valencia
country: Spain
facility: H.C.U.Valencia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
References: