AzTrials
AzTrials

Brain TumorsPhase 2/3NCT02066220

International Society of Paediatric Oncology (SIOP) PNET 5 Medulloblastoma

A Phase 2/3 study testing Radiotherapy without Carboplatin, Reduced-intensity maintenance chemotherapy and Radiotherapy with Carboplatin in people with Brain Tumors, run by Universitätsklinikum Hamburg-Eppendorf at 77 sites in 16 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 3 to 21 years
Conditions the study is for
Brain Tumors
What is being tested?
Radiotherapy without Carboplatin, Reduced-intensity maintenance chemotherapy and Radiotherapy with Carboplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
360 participants
Where
77 sitesin 16 countries
Study dates
Jun 2014to Dec 2026
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
  • 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.
  • 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
Show all 20Show fewer
  • 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.
  • 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.
  • No amplification of MYC or MYCN (determined by FISH).
  • 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).
  • No prior therapy for medulloblastoma other than surgery.
  • 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.
  • 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.
  • Common toxicity criteria (CTC) grades < 2 for liver, renal, haematological function
  • 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.
  • 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.
  • No identified Turcot and Li Fraumeni syndrome.
  • 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.
  • National and local ethical committee approval according to the laws of each participating country (to include approval for biological studies).

Who cannot join

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

Trial locations and contacts

77 sites in 16 countries.

77 sites in 16 countries

Germany59 sites

  • University Hospital Aachen

    Aachen, 52074

  • Klinikum Augsburg

    Augsburg, 86156

  • Helios Klinikum Berlin-Buch

    Berlin, 13125

  • Charite Campus, University of Berlin

    Berlin, 13353

  • Evangelisches Krankenhaus Bielefeld

    Bielefeld, 33617

  • University Hospital Bonn

    Bonn, 53113

  • Klinikum Braunschweig

    Braunschweig, 38118

  • Klinikum Bremen-Mitte

    Bremen, 28177

  • Klinikum Chemnitz

    Chemnitz, 09116

  • Kliniken der Stadt Köln

    Cologne, 50735

  • University Hospital Cologne

    Cologne, 50924

  • Carl-Thiem-Klinikum Cottbus

    Cottbus, 03048

  • Vestische Kinder- und Jugendklinik, University Witten/Herdecke

    Datteln, 45711

  • Klinikum Dortmund

    Dortmund, 44137

  • University Hospital Dresden

    Dresden, 01307

  • Klinikum Duisburg

    Duisburg, 47055

  • University Hospital Düsseldorf

    Düsseldorf, 40225

  • HELIOS Klinikum-Erfurt

    Erfurt, 99089

  • University Hospital Erlangen

    Erlangen, 91054

  • University Hospital Essen

    Essen, 45147

  • University Hospital Frankfurt/Main

    Frankfurt, 60590

  • University Hospital Freiburg

    Freiburg im Breisgau, 79106

  • University Hospital Gießen and Marburg

    Giessen, 35392

  • University Hospital Göttingen

    Göttingen, 37075

  • University Hospital Greifswald

    Greifswald, 17475

  • University Hospital Halle/Saale

    Halle, 06120

  • University Medical Center Hamburg-Eppendorf

    Hamburg, 20246

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • Angelika-Lautenschläger-Klinik

    Heidelberg, 69120

  • Gemeinschaftskrankenhaus Herdecke

    Herdecke, 58313

  • University Hospital Homburg/Saar

    Homburg, 66421

  • University Hospital Jena

    Jena, 07740

  • Städtisches Klinikum Karlsruhe

    Karlsruhe, 76133

  • Klinikum Kassel

    Kassel, 34125

  • UK-SH Campus Kiel

    Kiel, 24105

  • Gemeinschaftsklinikum Koblenz-Mayen

    Koblenz, 56073

  • HELIOS Klinikum Krefeld

    Krefeld, 47805

  • University Hospital Leipzig

    Leipzig, 04103

  • University Hospital Lübeck

    Lübeck, 23538

  • University Hospital Magdeburg

    Magdeburg, 39120

  • University Hospital Mainz

    Mainz, 55131

  • University Hospital Mannheim

    Mannheim, 68167

  • Johannes Wesling Klinikum Minden

    Minden, 32429

  • University Hospital München, Dr. von Haunersches Kinderspital

    München, 80337

  • Klinikum Schwabing, Pediatric Hospital of Technical University

    München, 80804

  • University Hospital Münster

    Münster, 48149

  • Cnopf'sche Kinderklinik

    Nuremberg, 90419

  • Klinikum Oldenburg

    Oldenburg, 26133

  • University Hospital Regensburg

    Regensburg, 93053

  • University Hospital Rostock

    Rostock, 18057

  • Asklepios Klinik Sankt Augustin

    Sankt Augustin, 53757

  • HELIOS-Kliniken Schwerin

    Schwerin, 19049

  • Klinikum Stuttgart

    Stuttgart, 70176

  • Mutterhaus der Borromäerinnen

    Trier, 54290

  • University Hospital Tübingen

    Tübingen, 72076

  • University Hospital Ulm

    Ulm, 89075

  • Dr. Horst Schmidt Kliniken

    Wiesbaden, 65199

  • Klinikum der Stadt Wolfsburg

    Wolfsburg, 38440

  • University Hospital Würzburg

    Würzburg, 97080

Other trials in Germany

France4 sites

  • CHU de Grenoble

    Grenoble, 38045

  • Institute Curie

    Paris, 75231

  • CHU-TOURS - Hôpital Clocheville

    Tours, 37044

  • Hôpital NANCY-BRABOIS

    Vandœuvre-lès-Nancy, 54500

Other trials in France

Austria1 site

  • Medical University of Graz

    Graz, 8010

Other trials in Austria

Belgium1 site

  • University Hospital Gasthuisberg

    Leuven, 3000

Other trials in Belgium

Czechia1 site

  • University Hospital Brno

    Brno, 61300

Other trials in Czechia

Denmark1 site

  • Rigshospitalet

    Copenhagen, 2100

Other trials in Denmark

Ireland1 site

  • Our Lady's Children's Hospital

    Dublin, 12

Other trials in Ireland

Italy1 site

  • Fondazione IRCCS Istituto Nazionale Tumori

    Milan, 20133

Other trials in Italy

Netherlands1 site

  • Prinses Máxima Center for Pediatric Oncology

    Bilthoven, 3720

Other trials in Netherlands

Norway1 site

  • Rigshospitalet

    Oslo, 0424

Other trials in Norway

Poland1 site

  • The Children's Memorial Health Institute

    Warsaw, 04-730

Other trials in Poland

Portugal1 site

  • University Hospital S.Joao

    Porto, 4200

Other trials in Portugal

Spain1 site

  • Oncology Hospital Cruces Bilbao

    Barakaldo, 48903

Other trials in Spain

Sweden1 site

  • Barncancercentrum Drottning Silvias Barnochungdomssjukhus

    Göteburg, 41685

Other trials in Sweden

Switzerland1 site

  • University Children's Hospital

    Zurich, 8032

Other trials in Switzerland

United Kingdom1 site

  • Great Ormond Street Hospital

    London, WC1N 3JH

Other trials in United Kingdom

About this study

Official title: AN INTERNATIONAL PROSPECTIVE TRIAL ON MEDULLOBLASTOMA (MB) IN CHILDREN OLDER THAN 3 TO 5 YEARS WITH WNT BIOLOGICAL PROFILE (PNET 5 MB - LR and PNET 5 MB - WNT-HR), AVERAGE-RISK BIOLOGICAL PROFILE (PNET 5 MB -SR), OR TP53 MUTATION, AND REGISTRY FOR MB OCCURRING IN THE CONTEXT OF GENETIC PREDISPOSITION

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.

Read the detailed description

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.

Conditions
Brain Tumors
Being tested
Radiotherapy without Carboplatin, Reduced-intensity maintenance chemotherapy, Radiotherapy with Carboplatin, Maintenance chemotherapy, WNT-HR < 16 years
Keywords
pediatric brain tumor, medulloblastoma, event-free survival (EFS), progression-free survival (PFS), overall survival (OS), PNET, posterior fossa, chemotherapy, radiotherapy, biological profile, ß-catenin
Medical subject headings
Brain Neoplasms, Medulloblastoma, Neuroectodermal Tumors, Primitive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Radiotherapy without CarboplatinRadiation

    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

  • Reduced-intensity maintenance chemotherapyDrug

    Also called Cisplatin, Lomustin (CCNU), Vincristine, Cyclophosphamide

    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.

  • Radiotherapy with CarboplatinRadiation

    Also called 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.

  • Maintenance chemotherapyDrug

    Also called Cisplatin, Lomustine (CCNU), Vincristine, Cyclophosphamide

    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).

  • WNT-HR < 16 yearsRadiation

    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

  • WNT-HR >= 16 yearsRadiation

    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

  • Induction ChemotherapyDrug

    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

  • SHH-TP53 M0Radiation

    • 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)

  • SHH-TP53 M+ (germline)Radiation

    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

  • SHH-TP53 (somatic)Radiation

    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

  • Vinblastin MaintenanceDrug

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

Study groups in NCT02066220
Study groupRoleWhat they receive
PNET 5 MB-LR (low-risk)ExperimentalRadiotherapy and reduced-intensity maintenance chemotherapy. Total treatment duration is 39 weeks.
Receives: Radiation: Radiotherapy without Carboplatin; Drug: Reduced-intensity maintenance chemotherapy
PNET 5 MB-SR (standard-risk)ExperimentalRadiotherapy with carboplatin or radiotherapy without carboplatin and maintenance chemotherapy. Total treatment duration is 48 weeks.
Receives: Radiation: Radiotherapy without Carboplatin; Radiation: Radiotherapy with Carboplatin; Drug: Maintenance chemotherapy
PNET 5 MB WNT-HRExperimentalRadiotherapy adapted to age and metastatic Status and maintenance chemotherapy adapted to age. Total treatment duration is 39 to 48 weeks.
Receives: Drug: Maintenance chemotherapy; Radiation: WNT-HR < 16 years; Radiation: WNT-HR >= 16 years
PNET 5 MB SHH-TP53ExperimentalReduced 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
Receives: Drug: Induction Chemotherapy; Radiation: SHH-TP53 M0; Radiation: SHH-TP53 M+ (germline); Radiation: SHH-TP53 (somatic); Drug: Vinblastin Maintenance

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 3-year Event-Free Survival (EFS)

    Measured: LR-arm after 9 years, SR-arm after 105 events (approx. 10 years)

Secondary outcomes (10)

  1. Overall survival

    Measured: 10 years

  2. Pattern of relapse

    Defined in 5 categorical variables:

    no relapse, local relapse, distant relapse, local and distant relapse, death

    Measured: 10 years

  3. Late effects of therapy on endocrine function

    measured as

    1. subfertility (FSH > 15 IU/L)
    2. endocrine deficits (hormone supplementation necessary)
    3. growth retardation (calculated as the difference in height standard deviation score from diagnose) 2 and 5 years after diagnosis and age of 18 years

    Measured: 10 years

  4. Late effects of therapy on audiology

    measured on audiogram performed 2 years after diagnosis, grading according to Chang ototoxicity grading (Chang and Chinosornvatana 2010)

    Measured: 8 years

  5. Late effects of therapy on neurology

    Measured as

    1. presence, duration, and therapy of hydrocephalus symptoms (pre- and post-operatively)
    2. presence of posterior fossa syndrome (cerebellar mutism survey after surgery, before radiotherapy)
    3. cerebellar symptoms (brief ataxia rating scales 2 and 5 years after diagnosis and age of 18 years)
    4. presence of symptoms for brain nerve dysfunction (2 and 5 years after diagnosis and age of 18 years)

    Measured: 10 years

  6. Late effects of therapy on quality of survival

    measured with standardized questionnaires/ scores:

    1. HUI3 (health status)
    2. BRIEF (executive functions)
    3. SDQ (behavioural outcome)
    4. PedsQL (quality of life)
    5. QLQ-C30 (quality of life)
    6. MEES (neurological function, educational provision)
    7. MFI (fatigue) 2 and 5 years after diagnosis and age of 18 years

    Measured: 10 years

  7. Progression-free survival

    Measured: 10 years

  8. Feasibility of carboplatin treatment

    measured as timely delivery of chemotherapy number of interruptions days during radiotherapy toxicities within 8 weeks after end of radiotherapy

    Measured: approx. 7 years

  9. Residual tumor

    measured by central MRI review postoperatively

    Measured: 6 years

  10. Leukoencephalopathy grading

    measured 2 years after diagnosis grades 0, 1, 2, 3, 4

    Measured: 8 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2014 (estimated)
  2. Study startJun 2014
  3. Primary completionDec 2026 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
360 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02066220
Sponsor's protocol ID
SIOP PNET 5 MB
Other IDs
2011-004868-30
Status last verified
Nov 2025
First submitted
7 Feb 2014
Last updated
4 Dec 2025
Results posted
No
Data monitoring committee
Yes

Publications

  • Mikkelsen MK, Pinto SN, Chiang J, Shimony N, Gajjar A. Evolving Biology and Therapy of WNT-Activated Medulloblastoma. J Natl Compr Canc Netw. 2025 Sep 18;23(10):e257061. doi: 10.6004/jnccn.2025.7061.

    PubMed 40967259

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Radiotherapy without Carboplatin, Reduced-intensity maintenance chemotherapy and Radiotherapy with Carboplatin in people with Brain Tumors, run by Universitätsklinikum Hamburg-Eppendorf at 77 sites in 16 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 4 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 77 sites in Germany, France, Austria, Belgium, Czechia and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

3-year Event-Free Survival (EFS) (time frame: LR-arm after 9 years, SR-arm after 105 events (approx. 10 years)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02066220, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2025.

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Clinical Trial NCT02066220 | AzTrials