International Society of Paediatric Oncology (SIOP) PNET 5 Medulloblastoma

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International Society of Paediatric Oncology (SIOP) PNET 5 Medulloblastoma

Study Purpose

The study PNET 5 MB has been designed for children with medulloblastoma of standard risk (according to the risk-group definitions which have been used so far; e.g. in PNET 4). With the advent of biological parameters for stratification into clinical medulloblastoma trials, the ß-catenin status will be the only criterion according to which study patients will be assigned to either treatment arm PNET 5 MB

- LR or to PNET 5 MB - SR, respectively.

The initial diagnostic assessments (imaging, staging, histology, and tumor biology) required for study entry are the same for both treatment arms. With the amendment for version 12 of the protocol, patients who have a WNT-activated medulloblastoma with clinically high-risk features can be included in the PNET 5 MB WNT-HR study, and patients with a high-risk SHH medulloblastoma with TP53 mutation (both somatic or germline including mosaicism) can be included in the PNET5 MB SHH-TP53 study. Data on patients with pathogenic germline alteration or cancer predisposition syndrome, who cannot be included in any prospective trial due to unavailability or due to physician or family decision, can be documented within the observational PNET 5 MB registry.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	3 Years - 21 Years
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Age at diagnosis, at least 3

- 5 years (depending on the country) and less than 22 years (LR-arm: less than 16 years).

The date of diagnosis is the date on which surgery is undertaken. 2. Histologically proven medulloblastoma, including the following subtypes, as defined in the WHO classification (2007): classic medulloblastoma, desmoplastic/nodular medulloblastoma. Pre-treatment central pathology review is considered mandatory. 3. Standard-risk medulloblastoma, defined as;

- total or near total surgical resection with less than or equal to 1.5 cm2 (measured on axial plane) of residual tumour on early post-operative MRI, without and with contrast, on central review; - no central nervous system (CNS) metastasis on MRI (cranial and spinal) on central review; - no tumour cells on the cytospin of lumbar CSF.

- no clinical evidence of extra-CNS metastasis; Patients with a reduction of postoperative residual tumor through second surgery to less than or equal to 1.5 cm2 are eligible, if if timeline for start of radiotherapy can be kept.

4. Submission of high quality biological material including fresh frozen tumor samples for the molecular assessment of biological markers (such as the assessment of myelocytomatosis oncogene (MYC) copy number status) in national biological reference centers. Submission of blood is mandatory for all patients, who agree on germline DNA studies. Submission of CSF is recommended. 5. No amplification of MYC or MYCN (determined by FISH). 6. For LR-arm: Low-risk biological profile, defined as WNT subgroup positivity. The WNT subgroup is defined by the presence of (i) ß-catenin mutation (mandatory testing), or (ii) ß-catenin nuclear immuno-positivity by IHC (mandatory testing) and ß-catenin mutation, or (iii) ß-catenin nuclear immuno-positivity by IHC and monosomy 6 (optional testing). For SR-arm: average-risk biological profile, defined as ß-catenin nuclear immuno-negativity by IHC (mandatory) and mutation analysis (optional). 7. No prior therapy for medulloblastoma other than surgery. 8. Radiotherapy aiming to start no more than 28 days after surgery. Foreseeable inability to start radiotherapy within 40 days after surgery renders patients ineligible for the study. 9. Screening for the compliance with eligibility criteria should be completed, and patient should be included into the study within 28 days after first surgery (in case of second surgery within 35 days after first surgery). Inclusion of patients is not possible later than 40 days after first tumour surgery, or after start of radiotherapy. 10. Common toxicity criteria (CTC) grades < 2 for liver, renal, haematological function. 11. no significant sensorineural hearing deficit as defined by pure tone audiometry with bone conduction or air conduction and normal tympanogram showing no impairment ≥ 20 decibel (dB) at 1-3 kilohertz (kHz). If performance of pure tone audiometry is not possible postoperatively, normal otoacoustic emissions are acceptable, if there is no history for hearing deficit. 12. No medical contraindication to radiotherapy or chemotherapy, such as preexisting DNA breakage syndromes (e.g. Fanconi Anemia, Nijmegen breakage syndrome), Gorlin Syndrome or other reasons as defined by patient's clinician. 13. No identified Turcot and Li Fraumeni syndrome. 14. Written informed consent (and patient assent where appropriate) for therapy according to the laws of each participating country. Information must be provided to the patient on biological studies (tumour and germline), and written informed consent obtained of agreement for participation. 15. National and local ethical committee approval according to the laws of each participating country (to include approval for biological studies).

Exclusion Criteria:

1. One of the inclusion criteria is lacking. 2. Brainstem or supratentorial primitive neuro-ectodermal tumour. 3. Atypical teratoid rhabdoid tumour. 4. Medulloepithelioma; Ependymoblastoma. 5. Large-cell medulloblastoma, anaplastic medulloblastoma, or medulloblastoma with extensive nodularity (MBEN), centrally confirmed. 6. Unfavourable or undeterminable biological profile, defined as amplification of MYC or MYCN, or MYC or MYCN or WNT subgroup status not determinable. 7. Metastatic medulloblastoma (on CNS MRI and/or positive cytospin of postoperative lumbar CSF). 8. Patient previously treated for a brain tumour or any type of malignant disease. 9. DNA breakage syndromes (e.g. Fanconi anemia, Nijmegen breakage syndrome) or other, or identified Gorlin,Turcot, or Li Fraumeni syndrome. 10. Patients who are pregnant. 11. Female patients who are sexually active and not taking reliable contraception. 12. Patients who cannot be regularly followed up due to psychological, social, familial or geographic reasons. 13. Patients in whom non-compliance with toxicity management guidelines can be expected.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT02066220
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2/Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Universitätsklinikum Hamburg-Eppendorf
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Francois Doz, Prof. Dr.Till Milde, Dr. med.
Principal Investigator Affiliation	Institut Curie Paris, FranceHopp Children´s Tumor Center at the NCT (KiTZ) and German Cancer Research Center
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Active, not recruiting
Countries	Austria, Belgium, Czechia, Denmark, France, Germany, Ireland, Italy, Netherlands, Norway, Poland, Portugal, Spain, Sweden, Switzerland, United Kingdom
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Brain Tumors

Additional Details

The aim of the LR-study is to confirm the high rate of event-free survival in patients between the ages of 3 to 5 years and less than 22, with 'standard risk' medulloblastoma with a low-risk biological profile. Patients eligible for the study will be those with non-metastatic medulloblastoma (by CSF cytology and centrally reviewed MRI imaging) at diagnosis and low-risk biological profile, defined as ß-catenin nuclear immuno-positivity by immuno-histochemistry (IHC). Patients will have undergone total or near-total tumour resection and will receive conventionally fractionated (once a day) radiotherapy with a dose of 54 Gy to the primary tumor and 18.0 Gy to the craniospinal axis. Following radiotherapy, patients will receive a reduced-intensity chemotherapy with a total of 6 cycles of chemotherapy consisting of 3 courses of cisplatin, CCNU and vincristine alternating with 3 courses of cyclophosphamide and vincristine. The aim of the SR-study is to test whether concurrent carboplatin during radiotherapy followed by 8 cycles of maintenance chemotherapy in patients with 'standard risk' medulloblastoma with an average-risk biological profile may improve outcome. Patients eligible for the study will be those with non-metastatic medulloblastoma (by CSF cytology and centrally reviewed MRI imaging) at diagnosis and average-risk biological profile, defined as ß-catenin nuclear immuno-negativity by IHC. Patients will have undergone total or near-total tumour resection and will receive conventionally fractionated (once a day) radiotherapy with a dose of 54 Gy to the primary tumor and 23.4 Gy to the craniospinal axis. Following radiotherapy, patients will receive a modified-intensity chemotherapy with a total of 8 cycles of chemotherapy consisting of 4 courses of cisplatin, CCNU and vincristine alternating with 4 courses of cyclophosphamide and vincristine. The primary aim of the WNT-HR study is to maintain a 3-year EFS over 80 %. The small number of patients does not allow neither conventional methods of test size and power, nor strict stopping rules. The 3-year EFS will be estimated by the Kaplan-Meier method at the end of the trial and its two-sided 95 % confidence interval will be calculated. The primary endpoint of the SHH-TP53 study is event-free survival (EFS). The aim of the study is the comparison of EFS between patients receiving a dose reduced induction chemotherapy, radiotherapy and maintenance chemotherapy and a historic population from unpublished data.

Arms & Interventions

Arms

Experimental: PNET 5 MB-LR (low-risk)

Radiotherapy and reduced-intensity maintenance chemotherapy. Total treatment duration is 39 weeks.

Experimental: PNET 5 MB-SR (standard-risk)

Radiotherapy with carboplatin or radiotherapy without carboplatin and maintenance chemotherapy. Total treatment duration is 48 weeks.

Experimental: PNET 5 MB WNT-HR

Radiotherapy adapted to age and metastatic Status and maintenance chemotherapy adapted to age. Total treatment duration is 39 to 48 weeks.

Experimental: PNET 5 MB SHH-TP53

Reduced chemotherapy with Doxorubicin, VCR, HD-MTX, Carboplatin, and MTX intraventricularly Stratification of radiotherapy according to - presence of metastasis - germline mutation in TP53 (including mosaicism) Maintenance chemotherapy with VBL Total treatment duration is 1 year

Interventions

Radiation: - Radiotherapy without Carboplatin

Brain - 23.40 Gy in 13 daily fractions of 1.80 Gy Spine - 23.40 Gy in 13 daily fractions of 1.80 Gy Primary tumour boost - 30.60 Gy in 17 daily fractions of 1.80 Gy Total dose - 54 Gy Duration of radiotherapy 6 weeks LR Arm after Amendment (Protocol version 11- 17 Nov 2014): Brain - 18.0 Gy in 10 daily fractions of 1.80 Gy Spine - 18.0 Gy in 10 daily fractions of 1.80 Gy Primary tumour boost - 36.0 Gy in 20 daily fractions of 1.80 Gy Total dose - 54 Gy Duration of radiotherapy 6 weeks

Drug: - Reduced-intensity maintenance chemotherapy

Starts 6 weeks after radiotherapy. 6 cycles alternating Regimen A and Regimen B. Regimen A (cycles 1, 3, 5): cisplatin 70 mg/m2 day 1, CCNU 75 mg/m2 day 1, vincristine 1.5 mg/m2 days 1, 8 and 15, Regimen B: (cycles 2, 4, 6): cyclophosphamide 1 x 1000 mg/m2 days 1-2, vincristine 1.5 mg/m2 day 1. Interval after cycle A: 6 weeks, after cycle B: 3 weeks, for a total duration of 27 weeks. Cumulative doses of chemotherapy drugs: cisplatin 210 mg/m2, lomustine (CCNU) 225 mg/m2, vincristine 18 mg/m2, cyclophosphamide 6 g/m2.

Radiation: - Radiotherapy with Carboplatin

Brain - 23.40 Gy in 13 daily fractions of 1.80 Gy Spine - 23.40 Gy in 13 daily fractions of 1.80 Gy Primary tumour boost - 30.60 Gy in 17 daily fractions of 1.80 Gy Total dose - 54 G Carboplatin 35 mg/m2 5 times/week.

Drug: - Maintenance chemotherapy

Starts 6 weeks after radiotherapy. 8 cycles alternating Regimen A and Regimen B. Regimen A (cycles 1, 3, 5, 7): cisplatin 70 mg/m2 day 1, CCNU 75 mg/m2 day 1, vincristine 1.5 mg/m2 days 1, 8 and 15 Regimen B: (cycles 2, 4, 6, 8): cyclophosphamide 1 x 1000 mg/m2 days 1-2, vincristine 1.5 mg/m2 day 1. Interval after cycle A: 6 weeks, after cycle B: 3 weeks. Duration 36 weeks. Cumulative doses of chemotherapy drugs: cisplatin 280 mg/m2, lomustine (CCNU) 300 mg/m2, vincristine 24 mg/m2, cyclophosphamide 8 g/m2, carboplatin 1050 mg/m2 (in randomized patients).

Radiation: - WNT-HR < 16 years

Brain - 23.4 Gy in 13 daily fractions of 1.8 Gy Spine - 23.4 Gy in 13 daily fractions of 1.8 Gy Primary tumour boost - 30.6 Gy in 17 daily fractions of 1.8 Gy Boost to macroscopic metastases - 21.6 Gy in 12 daily fractions of 1.8 Gy Total dose to primary tumour - 54.0 Gy in 30 daily fractions of 1.8 Gy Total dose to cranial metastases - 45.0 Gy in 25 daily fractions of 1.8 Gy Total dose to spinal metastases - 45.0 Gy in 25 daily fractions of 1.8 Gy

Radiation: - WNT-HR >= 16 years

Brain - 36.0 Gy in 20 daily fractions of 1.8 Gy Spine - 36.0 Gy in 20 daily fractions of 1.8 Gy Primary tumour boost - 18.0 Gy in 10 daily fractions of 1.8 Gy Metastases boost (cranial) - 14.4 Gy in 8 daily fractions of 1.8 Gy Metastases boost (spinal) - 9.0 Gy in 5 daily fractions of 1.8 Gy Total dose to primary tumour - 54.0 Gy in 30 daily fractions of 1.8 Gy Total dose to cranial metastases - 50.4 Gy in 30 daily fractions of 1.8 Gy Total dose to spinal metastases - 45.0 Gy in 25 daily fractions of 1.8 Gy

Drug: - Induction Chemotherapy

Doxorubicin 37,5mg/m² in 24h-infusion, days 1 and 2 (If administration of doxorubicin is not deemed appropriate, doxorubicin can be substituted by carboplatin 200mg/m²) VCR 1,5mg/m² (max. dose 2mg) in short infusion, days 1, 15, 29, 43 HD-MTX 5g/m²in two doses (0.5g/m² in 0.5h and 4.5g/m² in 23.5h), days 15 and 29 (+ Leucovorin) Carboplatin 200mg/m² in 1h-infusion, days 43, 44, and 45 MTX 2mg intraventricularly, days 1-4, 15, 16, 29, 30, 43-46

Radiation: - SHH-TP53 M0

- with VCR 1,5 mg/m2 (max. 2mg), once weekly during radiotherapy, for a maximum of 6 weeks - clinical target volume (CTV): safety margin along typical spread 10 mm: 23.4.Gy in 13 fractions to CTV. - focal RT boost to tumour bed and residual tumour (GTV) (boost: 30.6 Gy in 17 daily fractions of 1.8 Gy)

Radiation: - SHH-TP53 M+ (germline)

craniospinal radiotherapy with boost to tumour bed, residual tumour and metastatic deposits with VCR 1,5 mg/m2 (max. 2mg), once weekly during radiotherapy, for a maximum of 6 weeks Brain - 23.4 Gy in 13 daily fractions of 1.8 Gy Spine - 23.4 Gy in 13 daily fractions of 1.8 Gy Primary tumour boost - 30.6 Gy in 17 daily fractions of 1.8 Gy Metastases boost (cranial) - 30.6 Gy in 17 daily fractions of 1.8 Gy Metastases boost (spinal) - 21.6 Gy in 12 daily fractions of 1.8 Gy Total dose to primary tumour - 54.0 Gy in 30 daily fractions of 1.8 Gy Total dose to cranial metastases - 54.0 Gy in 30 daily fractions of 1.8 Gy Total dose to spinal metastases - 45.0 Gy in 25 daily fractions of 1.8 Gy

Radiation: - SHH-TP53 (somatic)

craniospinal radiotherapy with boost to tumour bed, residual tumour and metastatic deposits with VCR 1,5 mg/m2 (max. 2mg), once weekly during radiotherapy, for a maximum of 6 weeks Brain - 36.0 Gy in 20 daily fractions of 1.8 Gy Spine - 36.0 Gy in 20 daily fractions of 1.8 Gy Primary tumour boost - 18.0 Gy in 10 daily fractions of 1.8 Gy Metastases boost (cranial) - 18.0 Gy in 10 daily fractions of 1.8 Gy Metastases boost (spinal) - 9.0 Gy in 5 daily fractions of 1.8 Gy Total dose to primary tumour - 54.0 Gy in 30 daily fractions of 1.8 Gy Total dose to cranial metastases - 54.0 Gy in 30 daily fractions of 1.8 Gy Total dose to spinal metastases - 45 Gy in 25 daily fractions of 1.80 Gy

Drug: - Vinblastin Maintenance

Weekly VBL (5mg/m², max. 10mg/dose) for 24 weeks

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Medical University of Graz, Graz 2778067, Austria

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Medical University of Graz

Graz 2778067, , 8010

University Hospital Gasthuisberg, Leuven 2792482, Belgium

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University Hospital Gasthuisberg

Leuven 2792482, , 3000

University Hospital Brno, Brno 3078610, Czechia

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University Hospital Brno

Brno 3078610, , 61300

Rigshospitalet, Copenhagen 2618425, Denmark

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Rigshospitalet

Copenhagen 2618425, , 2100

CHU de Grenoble, Grenoble 3014728, France

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CHU de Grenoble

Grenoble 3014728, , 38045

Institute Curie, Paris 2988507, France

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Institute Curie

Paris 2988507, , 75231

CHU-TOURS - Hôpital Clocheville, Tours 2972191, France

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CHU-TOURS - Hôpital Clocheville

Tours 2972191, , 37044

Hôpital NANCY-BRABOIS, Vandœuvre-lès-Nancy 2970797, France

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Hôpital NANCY-BRABOIS

Vandœuvre-lès-Nancy 2970797, , 54500

University Hospital Aachen, Aachen 3247449, Germany

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University Hospital Aachen

Aachen 3247449, , 52074

Klinikum Augsburg, Augsburg 2954172, Germany

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Klinikum Augsburg

Augsburg 2954172, , 86156

Helios Klinikum Berlin-Buch, Berlin 2950159, Germany

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Helios Klinikum Berlin-Buch

Berlin 2950159, , 13125

Charite Campus, University of Berlin, Berlin 2950159, Germany

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Charite Campus, University of Berlin

Berlin 2950159, , 13353

Evangelisches Krankenhaus Bielefeld, Bielefeld 2949186, Germany

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Evangelisches Krankenhaus Bielefeld

Bielefeld 2949186, , 33617

University Hospital Bonn, Bonn 2946447, Germany

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University Hospital Bonn

Bonn 2946447, , 53113

Klinikum Braunschweig, Braunschweig 2945024, Germany

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Klinikum Braunschweig

Braunschweig 2945024, , 38118

Klinikum Bremen-Mitte, Bremen 2944388, Germany

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Klinikum Bremen-Mitte

Bremen 2944388, , 28177

Klinikum Chemnitz, Chemnitz 2940132, Germany

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Klinikum Chemnitz

Chemnitz 2940132, , 09116

Kliniken der Stadt Köln, Cologne 2886242, Germany

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Kliniken der Stadt Köln

Cologne 2886242, , 50735

University Hospital Cologne, Cologne 2886242, Germany

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University Hospital Cologne

Cologne 2886242, , 50924

Carl-Thiem-Klinikum Cottbus, Cottbus 2939811, Germany

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Carl-Thiem-Klinikum Cottbus

Cottbus 2939811, , 03048

Datteln 2938784, Germany

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Vestische Kinder- und Jugendklinik, University Witten/Herdecke

Datteln 2938784, , 45711

Klinikum Dortmund, Dortmund 2935517, Germany

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Klinikum Dortmund

Dortmund 2935517, , 44137

University Hospital Dresden, Dresden 2935022, Germany

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University Hospital Dresden

Dresden 2935022, , 01307

Klinikum Duisburg, Duisburg 2934691, Germany

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Klinikum Duisburg

Duisburg 2934691, , 47055

University Hospital Düsseldorf, Düsseldorf 2934246, Germany

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University Hospital Düsseldorf

Düsseldorf 2934246, , 40225

HELIOS Klinikum-Erfurt, Erfurt 2929670, Germany

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HELIOS Klinikum-Erfurt

Erfurt 2929670, , 99089

University Hospital Erlangen, Erlangen 2929567, Germany

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University Hospital Erlangen

Erlangen 2929567, , 91054

University Hospital Essen, Essen 2928810, Germany

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University Hospital Essen

Essen 2928810, , 45147

University Hospital Frankfurt/Main, Frankfurt 2925536, Germany

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University Hospital Frankfurt/Main

Frankfurt 2925536, , 60590

University Hospital Freiburg, Freiburg im Breisgau 2925177, Germany

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University Hospital Freiburg

Freiburg im Breisgau 2925177, , 79106

University Hospital Gießen and Marburg, Giessen 2920512, Germany

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University Hospital Gießen and Marburg

Giessen 2920512, , 35392

University Hospital Göttingen, Göttingen 2918632, Germany

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University Hospital Göttingen

Göttingen 2918632, , 37075

University Hospital Greifswald, Greifswald 2917788, Germany

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University Hospital Greifswald

Greifswald 2917788, , 17475

University Hospital Halle/Saale, Halle 2911522, Germany

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University Hospital Halle/Saale

Halle 2911522, , 06120

Hamburg 2911298, Germany

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University Medical Center Hamburg-Eppendorf

Hamburg 2911298, , 20246

Medizinische Hochschule Hannover, Hanover 2910831, Germany

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Medizinische Hochschule Hannover

Hanover 2910831, , 30625

Angelika-Lautenschläger-Klinik, Heidelberg 2907911, Germany

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Angelika-Lautenschläger-Klinik

Heidelberg 2907911, , 69120

Gemeinschaftskrankenhaus Herdecke, Herdecke 2906152, Germany

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Gemeinschaftskrankenhaus Herdecke

Herdecke 2906152, , 58313

University Hospital Homburg/Saar, Homburg 2899449, Germany

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University Hospital Homburg/Saar

Homburg 2899449, , 66421

University Hospital Jena, Jena 2895044, Germany

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University Hospital Jena

Jena 2895044, , 07740

Städtisches Klinikum Karlsruhe, Karlsruhe 2892794, Germany

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Städtisches Klinikum Karlsruhe

Karlsruhe 2892794, , 76133

Klinikum Kassel, Kassel 2892518, Germany

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Klinikum Kassel

Kassel 2892518, , 34125

UK-SH Campus Kiel, Kiel 2891122, Germany

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UK-SH Campus Kiel

Kiel 2891122, , 24105

Gemeinschaftsklinikum Koblenz-Mayen, Koblenz 2886946, Germany

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Gemeinschaftsklinikum Koblenz-Mayen

Koblenz 2886946, , 56073

HELIOS Klinikum Krefeld, Krefeld 2884509, Germany

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HELIOS Klinikum Krefeld

Krefeld 2884509, , 47805

University Hospital Leipzig, Leipzig 2879139, Germany

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University Hospital Leipzig

Leipzig 2879139, , 04103

University Hospital Lübeck, Lübeck 2875601, Germany

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University Hospital Lübeck

Lübeck 2875601, , 23538

University Hospital Magdeburg, Magdeburg 2874545, Germany

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University Hospital Magdeburg

Magdeburg 2874545, , 39120

University Hospital Mainz, Mainz 2874225, Germany

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University Hospital Mainz

Mainz 2874225, , 55131

University Hospital Mannheim, Mannheim 2873891, Germany

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University Hospital Mannheim

Mannheim 2873891, , 68167

Johannes Wesling Klinikum Minden, Minden 2871039, Germany

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Johannes Wesling Klinikum Minden

Minden 2871039, , 32429

München 2867711, Germany

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University Hospital München, Dr. von Haunersches Kinderspital

München 2867711, , 80337

München 2867711, Germany

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Klinikum Schwabing, Pediatric Hospital of Technical University

München 2867711, , 80804

University Hospital Münster, Münster 2867543, Germany

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University Hospital Münster

Münster 2867543, , 48149

Cnopf'sche Kinderklinik, Nuremberg 2861650, Germany

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Cnopf'sche Kinderklinik

Nuremberg 2861650, , 90419

Klinikum Oldenburg, Oldenburg 2857458, Germany

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Klinikum Oldenburg

Oldenburg 2857458, , 26133

University Hospital Regensburg, Regensburg 2849483, Germany

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University Hospital Regensburg

Regensburg 2849483, , 93053

University Hospital Rostock, Rostock 2844588, Germany

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University Hospital Rostock

Rostock 2844588, , 18057

Asklepios Klinik Sankt Augustin, Sankt Augustin 2841648, Germany

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Asklepios Klinik Sankt Augustin

Sankt Augustin 2841648, , 53757

HELIOS-Kliniken Schwerin, Schwerin 2834282, Germany

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HELIOS-Kliniken Schwerin

Schwerin 2834282, , 19049

Klinikum Stuttgart, Stuttgart 2825297, Germany

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Klinikum Stuttgart

Stuttgart 2825297, , 70176

Mutterhaus der Borromäerinnen, Trier 2821164, Germany

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Mutterhaus der Borromäerinnen

Trier 2821164, , 54290

University Hospital Tübingen, Tübingen 2820860, Germany

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University Hospital Tübingen

Tübingen 2820860, , 72076

University Hospital Ulm, Ulm 2820256, Germany

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University Hospital Ulm

Ulm 2820256, , 89075

Dr. Horst Schmidt Kliniken, Wiesbaden 2809346, Germany

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Dr. Horst Schmidt Kliniken

Wiesbaden 2809346, , 65199

Klinikum der Stadt Wolfsburg, Wolfsburg 2806654, Germany

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Klinikum der Stadt Wolfsburg

Wolfsburg 2806654, , 38440

University Hospital Würzburg, Würzburg 2805615, Germany

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University Hospital Würzburg

Würzburg 2805615, , 97080

Our Lady's Children's Hospital, Dublin 2964574, Ireland

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Our Lady's Children's Hospital

Dublin 2964574, , 12

Milan 6951411, Italy

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Fondazione IRCCS Istituto Nazionale Tumori

Milan 6951411, , 20133

Bilthoven 2758927, Netherlands

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Prinses Máxima Center for Pediatric Oncology

Bilthoven 2758927, , 3720

Rigshospitalet, Oslo 3143244, Norway

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Rigshospitalet

Oslo 3143244, , 0424

The Children's Memorial Health Institute, Warsaw 756135, Poland

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The Children's Memorial Health Institute

Warsaw 756135, , 04-730

University Hospital S.Joao, Porto 2735943, Portugal

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University Hospital S.Joao

Porto 2735943, , 4200

Oncology Hospital Cruces Bilbao, Barakaldo 3109453, Spain

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Oncology Hospital Cruces Bilbao

Barakaldo 3109453, , 48903

Göteburg, Sweden

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Barncancercentrum Drottning Silvias Barnochungdomssjukhus

Göteburg, , 41685

University Children's Hospital, Zurich 2657896, Switzerland

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University Children's Hospital

Zurich 2657896, , 8032

Great Ormond Street Hospital, London 2643743, United Kingdom

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Great Ormond Street Hospital

London 2643743, , WC1N 3JH

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