Adult Study: ABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma Pediatric Study: Evaluation of ABT-414 in Children With High Grade Gliomas
- Conditions
- Glioblastoma
- Interventions
- Registration Number
- NCT02343406
- Lead Sponsor
- AbbVie
- Brief Summary
This study was conducted to evaluate the efficacy and safety of depatuxizumab mafodotin (ABT-414) alone or with temozolomide versus temozolomide or lomustine alone in adult participants with recurrent glioblastoma. The study also included a substudy to evaluate safety, tolerability and pharmacokinetics of ABT-414 in a pediatric population.
- Detailed Description
The study objectives were to assess whether depatuxizumab mafodotin (ABT-414) alone or in combination with temozolomide (TMZ) improved overall survival (OS), progression-free survival (PFS), tumor response, quality of life, neurological deterioration-free survival (NDFS), and steroid use compared to standard treatment with lomustine single agent or TMZ re-challenge in adult subjects ≥ 18 years of age with centrally-confirmed recurrent epidermal growth factor receptor (EGFR)-amplified glioblastoma. The safety, pharmacokinetics, and efficacy of depatuxizumab mafodotin in children \<18 years of age was evaluated in a pediatric substudy. The EMEA-001732-PIP02-15 pediatric investigation plan was withdrawn on 07 July 2019 due to the discontinuation of the depatuxizumab mafodotin research program.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 266
Adult participants (greater than or equal to 18 years old):
- Histologically confirmed de novo (primary) glioblastoma with unequivocal tumor progression or recurrence.
- In case of testing at the time of first progression: either at least 3 months after the end of radiotherapy or have tumor progression that is clearly outside the radiation field or have tumor progression unequivocally proven by surgery/biopsy
- Absence of any psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule; such conditions should be assessed with the patient before registration in the trial.
- Availability of adequate biological material (formalin-fixed paraffin embedded [FFPE] tumor) for central testing of Epithelial Growth Factor Receptor (EGFR) amplification
- Presence of EGFR amplification confirmed by central assessment; participants with undetermined EGFR status are excluded
- World Health Organization (WHO) Performance status 0 - 2
- No more than one line of chemotherapy (concurrent and adjuvant Temozolomide based chemotherapy including in combination with another investigational agent is considered one line of chemotherapy). Chemotherapy must have been completed at least 4 weeks prior to randomization.
- Post surgery MRI within 48 hours following surgery, however an MRI scan has to be done within 2 weeks prior to randomization.
- Surgery completed at least 2 weeks before randomization and patients should have fully recovered as assessed by investigators.
- Renal function: calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault formula.
- Liver function: bilirubin < 1.5× upper limit of the normal range (ULN), alkaline phosphatase and transaminases (ASAT) < 2.5× ULN
Pediatric sub-study participants (less than 18 years old):
- Histologically proven high grade glioma (HGG: WHO grade III glioma [e.g anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma], grade IV glioma [e.g. glioblastoma, gliosarcoma] or diffuse intrinsic pontine glioma [DIPG]).
- Must either have recurrent/progressive tumor or, if newly diagnosed, have completed any planned radiation therapy at least 4 weeks prior to first dose of ABT-414.
- The tumor tissue must have been determined to have EGFR amplification, (by local or other testing service).
- Availability of adequate biological material for retrospective confirmatory central testing of EGFR amplification
- Participant has sufficiently recovered from previous therapy. The investigator believes that benefit of treating the pediatric subject with ABT-414 outweighs the expected risks and that this treatment is in the best interests of the pediatric subject.
- Renal function: calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault formula for pediatric patients ≥12 years of age and estimated glomerular filtration rate ≥ 30 mL/min/1.73 m^2 by modified Schwartz equation for pediatric patients < 12 years of age.
- Liver function: Total bilirubin ≤ 1.5× upper limit of the normal range (ULN), Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) <= 3× ULN. Participants with Gilbert's syndrome documented in medical history may be enrolled if total bilirubin is < 3 times ULN. Not allowed are participants with known chronic liver disease and/or cirrhosis.
Adult population (greater than or equal to 18 years old):
- Prior treatment with nitrosoureas
- Prior treatment with bevacizumab
- Previous exposure to Epithelial Growth Factor Receptor (EGFR) targeted agents, including EGFRvIII targeting agents
- Prior discontinuation of temozolomide chemotherapy for toxicity reasons
- Prior Radiation Therapy (RT) with a dose over 65 Gy to the brain, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven
- Previous other malignancies, except for any previous malignancy which was treated with curative intent more than 5 years prior to randomization, and except for adequately controlled limited basal cell carcinoma of the skin, squamous carcinoma of the skin or carcinoma in situ of the cervix
- Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to randomization.
- No history of wheat allergies and Coeliac disease.
- No EIAED, patients who require anti-convulsant therapy must be taking non-enzyme inducing antiepileptic drugs (non-EIAED). Patients previously on EIAED must be fully switched to non-EIAED at least 2 weeks prior to randomization.
Pediatric sub-study (less than 18 years old):
- (For recurrent disease) No prior RT with a dose over 65 Gy to the brain, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven
- No current or recent (within 4 weeks or 5 half-lives [whichever is shorter] before enrollment) treatment with another investigational drug
- Female participants of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to randomization.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control_lomustine Lomustine Adult participants relapsing during temozolomide (TMZ) treatment or within the first 16 weeks after the first day of the last TMZ cycle received lomustine on Day 1 of every 42-day treatment period until one of the treatment withdrawal criteria was met, up to a maximum of 1 year. ABT-414/temozolomide Temozolomide Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants Control_ temozolomide Temozolomide Adult participants relapsing 16 weeks or more after the first day of the last temozolomide (TMZ) cycle received TMZ on Day 1 to Day 5 for the first 28-day cycle, with dose escalation in subsequent cycles in case of adequate tolerance and treatment continuing until one of the treatment withdrawal criteria was met. ABT-414_adult Depatuxizumab mafodotin Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to adult participants ABT-414/temozolomide Depatuxizumab mafodotin Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks in combination with temozolomide (TMZ) to adult participants ABT-414_ pediatric Depatuxizumab mafodotin Depatuxizumab mafodotin (ABT-414) administered once every 2 weeks to pediatric participants. Temozolomide (TMZ) was only allowed for pediatric participants if its use was in accordance with local clinical practice, and was not considered an investigational product for the study (unless this was a local requirement).
- Primary Outcome Measures
Name Time Method Adult Study: Overall Survival (OS) From the date of randomization up to the date of participant's death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months. Overall Survival (OS) was defined as time from randomization to death due to any cause, regardless of whether the event occurred on or off study drug (depatuxizumab mafodotin/temozolomide/lomustine).
Adult Study: Progression-Free Survival (PFS) Measured every 8 weeks from date of randomization until the date of first objective progression or subject's death, whichever occurred first, up to 2 years Progression-free survival was assessed per response assessment in neuro-oncology criteria (RANO) criteria and assessed by an independent review committee and was defined as the length of time during and after the treatment of a disease, that the participant lived with the disease but did not get worse.
Pediatric Study: Percentage of Participants With Adverse Events From the First Visit Until 49 Days After the Last Dose of Study Drug From participant's first visit until 49 days after the participant's last dose of study drug, up to 63 weeks The severity of each adverse event was rated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 4.0)
Pediatric Study: Maximum Observed Serum Concentration (Cmax) of ABT-414 Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose Cmax is the peak concentration that a drug achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
Pediatric Study: Maximum Observed Plasma Concentration (Cmax) of Cys-mcMMAF Samples collected Cycle 1 Days 1, 2, 3, 5, 8 Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose. Cys-mcMMAF is a toxic metabolite of depatuxizumab mafodotin.
Pediatric Study: Half-life (t1/2) Observed for ABT-414 Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose Half-life is the calculated time it takes for half of the drug to leave the body.
Pediatric Study: Half-life (t1/2) Observed for Cys-mcMMAF Samples collected Cycle 1 Days 1, 2, 3, 5, 8 Half-life is the calculated time it takes for half of the drug or drug metabolite to leave the body. CysmcMMAF is a toxic metabolite of depatuxizumab mafodotin.
Pediatric Study: Area Under the Concentration-time Curve (AUC) Observed for ABT-414 Samples collected Cycle 1 Days 1, 2,3,5,8,15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 5 Day 1; Day 1 of every two cycles starting with Cycle 5; and 35 days after the last dose AUC is a measure of how long and how much drug is present in the body after dosing. The AUC of depatuxizumab mafodotin (ABT-414) in the pediatric population was measured following treatment to confirm that this was comparable to adults, and that the dosing levels are appropriate for a pediatric population.
Pediatric Study: Area Under the Concentration-time-curve (AUC) Observed for Unconjugated Cys-mcMMAF Samples collected Cycle 1 Days 1, 2, 3, 5, 8 AUC is a measure of how long and how much drug or drug metabolite is present in the body after dosing. The AUC of Cys-mcMMAF, a toxic metabolite of depatuxizumab mafodotin, in the pediatric population was measured following treatment to confirm that this was comparable to adults, and that the dosing levels are appropriate for a pediatric population.
- Secondary Outcome Measures
Name Time Method Adult Study: Objective Response Rate (ORR) Every 8 weeks at each assessment of disease, up to 28 months The objective response rate (ORR) included best overall responses - complete response (CR) and partial response (PR) - assessed by the independent review committee per response assessment in neurooncology criteria (RANO) criteria from the date of randomization until disease progression or death, whichever came first. All objective responses (CR and PR) must be have been confirmed by repeat MRI 4 weeks after the first time when CR or PR is identified. Any subject who did not meet CR or PR including those who did not have post-baseline radiological assessments was considered a nonresponder.
Adult Study: Overall Survival in the Subgroup With Epidermal Growth Factor Receptor (EGFRvIII) Mutation From the date of randomization up to the date of participant's death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months Overall Survival (OS) was defined as time from randomization to death due to any cause, regardless of whether the event occurred on or off study drug (depatuxizumab mafodotin/temozolomide/lomustine) for all randomized participants that had the Epidermal Growth Factor Receptor (EGFRvIII) mutation.
Pediatric Study: Objective Response Rate (ORR) Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Pediatric Study: Best Tumor Response Rate Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Pediatric Study: Duration of Response Evaluated every 8 weeks (+/- 7 days) at each assessment of disease according to response assessment in neuro-oncology criteria (RANO), until progression or withdrawal up to approximately 52 weeks The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Pediatric Study: Overall Survival From the date of enrollment to the date of death; participants who completed treatment were to be assessed every 12 weeks, up to 28 months The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Pediatric Study: Time to Progression Evaluated every 8 weeks (+/- 7 days) from the date of enrollment until the date of first objective progression or participant's death, whichever occurs first, up to approximately 52 weeks The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/ temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, pediatric time to progression data analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Pediatric Study: Progression-Free Survival Evaluated every 8 weeks (+/- 7 days) from the date of enrollment until the date of first objective progression or participant's death, whichever occurs first, up to approximately 52 weeks The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Pediatric Study: Percentage of Participants With Changes in Neurological Status and Functioning Baseline, Day 1 and 15 of each cycle, every 6 months for 5 years thereafter, and then annually The pediatric data collection for this study was still ongoing when INTELLANCE-1 (NCT02573324; EudraCT number 2015-001166-26) interim efficacy results overall indicated no survival benefit to adding depatuxizumab mafodotin to standard radiotherapy/temozolomide therapy in newly diagnosed glioblastoma patients. Based on the INTELLANCE-1 results, AbbVie decided to stop further enrollment of pediatric participants into the pediatric substudy and to stop the collection of efficacy data. Because of this decision not to summarize except for safety data, the pediatric substudy ORR analysis was not summarized due to the small number of pediatric participants enrolled in the study.
Trial Locations
- Locations (102)
Hopital Pitie Salpetriere /ID# 145887
🇫🇷Paris, France
Fondazione IRCCS Istituto Neurologico Carlo Besta /ID# 140395
🇮🇹Milan, Italy
CHU-Hopital Avicenne /ID# 137910
🇫🇷Bobigny, Ile-de-France, France
Fakultni Nemocnice v Motole /ID# 139509
🇨🇿Prague 5, Praha 5, Czechia
FN Hradec Kralove /ID# 139510
🇨🇿Hradec Kralove, Czechia
Univ Hosp Ostrava-Poruba /ID# 139507
🇨🇿Ostrava, Czechia
Hospices Civils de Lyon /ID# 137913
🇫🇷Bron, France
Montreal Neurological Institut /ID# 136309
🇨🇦Montreal, Quebec, Canada
Samsung Medical Center /ID# 136842
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Universitaetsklinik Heidelberg /ID# 137924
🇩🇪Heidelberg, Baden-Wuerttemberg, Germany
Masarykuv onkologikcy ustav /ID# 139508
🇨🇿Brno, Czechia
Gustave Roussy /ID# 137912
🇫🇷Villejuif, Ile-de-France, France
Istituto Oncologico Veneto /ID# 138336
🇮🇹Padova, Italy
UZ Gent /ID# 152944
🇧🇪Gent, Oost-Vlaanderen, Belgium
CHU de Nice /ID# 137917
🇫🇷Nice CEDEX 1, Provence-Alpes-Cote-d Azur, France
Universitatsklinik Regensburg /ID# 137920
🇩🇪Ratisbon, Bayern, Germany
Centre Leon Berard /ID# 137918
🇫🇷Lyon CEDEX 08, Rhone, France
Institut de Cancer de l'Ouest /ID# 137909
🇫🇷Angers, France
UZ Leuven /ID# 137925
🇧🇪Leuven, Belgium
Ospedale Bellaria.Azienda USL IRCCS.Istituto delle Scienze Neurologiche di Bolog /ID# 138335
🇮🇹Bologna, Italy
Seoul National Univ Bundang ho /ID# 136841
🇰🇷Seongnam, Gyeonggido, Korea, Republic of
Univ Klinik Eppendorf Hamburg /ID# 137921
🇩🇪Hamburg, Germany
Hopital de la Timone /ID# 137911
🇫🇷Marseille CEDEX 05, Provence-Alpes-Cote-d Azur, France
Great Ormond St Hospital NHS /ID# 153421
🇬🇧London, United Kingdom
Universitatsklinikum Tubingen /ID# 137923
🇩🇪Tuebingen, Germany
Azienda Ospedaliera Sant' Andrea /ID# 138337
🇮🇹Rome, Italy
Cork University Hospital /ID# 136828
🇮🇪Cork, Ireland
National Cancer Ctr Singapore /ID# 135952
🇸🇬Singapore, Singapore
Seoul National University Hospital /ID# 136840
🇰🇷Seoul, Korea, Republic of
Hospital Universitario Nino /ID# 153800
🇪🇸Madrid, Spain
Uniwersyteckie Centrum Kliniczne /ID# 137919
🇵🇱Gdansk, Mazowieckie, Poland
Prinses Maxima Centrum /ID# 204409
🇳🇱Utrecht, Netherlands
Clinica Universitar de Navarra - Pamplona /ID# 140047
🇪🇸Pamplona, Navarra, Comunidad, Spain
Univ Hospitals Birmingham NHS Foundation trust /ID# 136978
🇬🇧Birmingham, United Kingdom
Gartnavel General Hospital /ID# 136979
🇬🇧Glasgow, United Kingdom
Hosp Univ 12 de Octubre /ID# 137908
🇪🇸Madrid, Spain
Guy's and St Thomas' NHS Found /ID# 140312
🇬🇧London, London, City Of, United Kingdom
University College Hospitals /ID# 136879
🇬🇧London, United Kingdom
Vrije Universiteit Medisch Centrum /ID# 137221
🇳🇱Amsterdam, Netherlands
Universitair Medisch Centrum Utrecht /ID# 137219
🇳🇱Utrecht, Netherlands
Sarah Cannon Research Institute at HealthONE - Denver /ID# 141798
🇺🇸Denver, Colorado, United States
Rush University Medical Center /ID# 137542
🇺🇸Chicago, Illinois, United States
Cleveland Clinic Main Campus /ID# 137540
🇺🇸Cleveland, Ohio, United States
University of Pittsburgh MC /ID# 134491
🇺🇸Pittsburgh, Pennsylvania, United States
UT Southwestern Medical Center /ID# 136718
🇺🇸Dallas, Texas, United States
Swedish Medical Center /ID# 136719
🇺🇸Seattle, Washington, United States
Royal Brisbane and Women's Hospital /ID# 147091
🇦🇺Herston, Queensland, Australia
Royal Adelaide Hospital /ID# 135208
🇦🇺Adelaide, South Australia, Australia
Turku University Hospital /ID# 140861
🇫🇮Turku, Finland
Helsinki Univ Central Hospital /ID# 140078
🇫🇮Helsinki, Finland
Helsinki Univ Central Hospital /ID# 153069
🇫🇮Helsinki, Finland
Wojewodzkie Wielospecjalistycz /ID# 137654
🇵🇱Lodz, Poland
Barwon Health University Hospital Geelong /ID# 134493
🇦🇺Geelong, Victoria, Australia
ZNA Middelheim /ID# 137926
🇧🇪Antwerp, Belgium
Pecsi Tudomanyegyetem /ID# 136111
🇭🇺Pécs, Pecs, Hungary
National University Hospital /ID# 135951
🇸🇬Singapore, Singapore
Centre Hospitalier Univ Vaudoi /ID# 137929
🇨🇭Lausanne, Switzerland
University Hospital Zurich /ID# 137930
🇨🇭Zurich, Switzerland
CHRU Lille - Hôpital Claude Huriez /ID# 137916
🇫🇷Lille CEDEX, Hauts-de-France, France
National Institute of Oncology /ID# 135970
🇭🇺Budapest, Hungary
University Hospital St. Polten /ID# 139070
🇦🇹St. Pölten, Niederoesterreich, Austria
Cliniques Universitaires Saint Luc /ID# 139391
🇧🇪Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium
AZ St-Jan Brugge-Oostende AV /ID# 137927
🇧🇪Brugge, West-Vlaanderen, Belgium
Institut de Cancer de l'Ouest /ID# 137914
🇫🇷St Herblain CEDEX, Loire-Atlantique, France
Hospital Zambrano Hellion /ID# 138076
🇲🇽San Pedro Garza García, Mexico
Centre Oscar Lambret /ID# 169619
🇫🇷Lille, Hauts-de-France, France
Debreceni Egyetem Klinikai Központ /ID# 135969
🇭🇺Debrecen, Hungary
Beaumont Hospital /ID# 136829
🇮🇪Dublin, Ireland
Orszagos Klinikai Idegtudomany /ID# 135971
🇭🇺Budapest, Hungary
Taichung Veterans General Hosp /ID# 136977
🇨🇳Taichung City, Taiwan
China Medical University Hosp /ID# 136976
🇨🇳Taichung City, Taichung, Taiwan
National Taiwan Univ Hosp /ID# 136975
🇨🇳Taipei City, Taipei, Taiwan
Lucile Packard Children's Hosp /ID# 153678
🇺🇸Palo Alto, California, United States
Univ of Colorado Cancer Center /ID# 134882
🇺🇸Aurora, Colorado, United States
Children's Hospital Colorado /ID# 153677
🇺🇸Aurora, Colorado, United States
Dana-Farber Cancer Institute /ID# 154210
🇺🇸Boston, Massachusetts, United States
Long Island Brain Tumor Center /ID# 134496
🇺🇸Lake Success, New York, United States
Weill Cornell Medicine /ID# 152656
🇺🇸New York, New York, United States
Tennessee Oncology, PLLC /ID# 134492
🇺🇸Nashville, Tennessee, United States
Port Macquarie Base Hospital /ID# 134569
🇦🇺Port Macquarie, New South Wales, Australia
Sydney Children's Hospital /ID# 153533
🇦🇺Randwick, New South Wales, Australia
Royal North Shore Hospital /ID# 147092
🇦🇺Saint Leonards, New South Wales, Australia
Calvary Mater Newcastle /ID# 134570
🇦🇺Waratah, New South Wales, Australia
Royal Hobart Hospital /ID# 135209
🇦🇺Hobart, Tasmania, Australia
Southern Medical Day Care Ctr /ID# 134495
🇦🇺Wollongong, New South Wales, Australia
Royal Children's Hospital /ID# 157624
🇦🇺Melbourne, Victoria, Australia
LKH-Univ. Klinikum Graz /ID# 139071
🇦🇹Graz, Austria
Kepler Universitätsklinikum GmbH - Neuromed Campus /ID# 139068
🇦🇹Linz, Austria
Grand Hôpital de Charleroi /ID# 139342
🇧🇪Charleroi, Hainaut, Belgium
LMU Klinikum der Universität München /ID# 137922
🇩🇪Munich, Germany
Erasmus Medisch Centrum /ID# 136981
🇳🇱Rotterdam, Netherlands
Semmelweis Egyetem /ID# 152578
🇭🇺Budapest, Hungary
Ospedale Generale di Bolzano /ID# 138338
🇮🇹Bolzano, Italy
Universitair Medisch Centrum Groningen /ID# 138266
🇳🇱Groningen, Netherlands
Haaglanden Medisch Centrum /ID# 137222
🇳🇱The Hague, Netherlands
KK Women's & Children Hospital /ID# 153676
🇸🇬Singapore, Singapore
Instituto Catalán de Oncología (ICO) Badalona /ID# 140976
🇪🇸Badalona, Barcelona, Spain
Instituto Catalan de Oncologia (ICO) & Hosp. de Bellvitge /ID# 137688
🇪🇸Barcelona, Spain
Taipei Veterans General Hosp /ID# 136974
🇨🇳Taipei City, Taiwan
Linkou Chang Gung Memorial Ho /ID# 136944
🇨🇳Taoyuan City, Taiwan
Hull and East Yorkshire NHS /ID# 136917
🇬🇧Hull, United Kingdom
Christie NHS Foundation Trust /ID# 140313
🇬🇧Manchester, United Kingdom