Brief description of trial (Data source: BASEC)
In dieser klinischen Forschungsstudie wird untersucht, ob die Studienmedikamente Dabrafenib in Kombination mit Trametinib bei Kindern und Jugendlichen, die an BRAF V600-Mutation-positiven Gliomen leiden, wirksam und sicher sind. An dieser Studie werden weltweit voraussichtlich 102 Patienten mit tiefgradigem Gliom und 40 Patienten mit hochgradigem Gliom teilnehmen.
Patienten mit hochgradigem Gliom erhalten die Studienmedikamente Dabrafenib und Trametinib.
Patienten mit tiefgradigem Gliom werden per Zufall einer von zwei Behandlungsgruppen zugeteilt. 68 Patienten werden die Studienbehandlung mit Dabrafenib und Trametinib erhalten. 34 Patienten werden zum Vergleich die für diese Erkrankung übliche Standard-Chemotherapie mit Carboplatin und Vincristin erhalten. Ist die Behandlung mit der Chemotherapie nicht erfolgreich, ist ein Wechsel in die Dabrafenib & Trametinib Behandlungsgruppe unter gewissen Voraussetzungen möglich.
Die Studienteilnehmer erhalten die Studienbehandlung so lange, wie sie nach Ansicht des zuständigen Studienarztes eine positive Wirkung hat.
Health conditions investigated(Data source: BASEC)
Kinder oder Jugendliche mit zwei Formen von Hirntumoren können an dieser Studie teilnehmen:
- Patienten mit einem BRAF V600-Mutation-positiven, refraktären oder rezidivierten, hochgradigen Gliom
- Patienten mit einem BRAF V600-Mutation-positiven tiefgradigen Gliom
Health conditions
(Data source: WHO)
Diffuse Astrocytoma;Anaplastic Astrocytoma;Astrocytoma;Oligodendroglioma, Childhood;Anaplastic Oligodendroglioma;Glioblastoma;Pilocytic Astrocytoma;Giant Cell Astrocytoma;Pleomorphic Xanthoastrocytoma;Anaplastic Pleomorphic Xanthoastrocytoma;Angiocentric Glioma;Chordoid Glioma of Third Ventricle;Gangliocytoma;Ganglioglioma;Anaplastic Ganglioglioma;Dysplastic Gangliocytoma of Cerebrellum;Desmoplastic Infantile Astrocytoma and Ganglioglioma;Papillary Glioneuronal Tumor;Rosette-forming Glioneurona Tumor;Central Neurocytoma;Extraventricular Neurocytoma;Cerebellar Iponeurocytoma
Rare disease
(Data source: BASEC)
No
Intervention investigated (e.g. drug, therapy or campaign)
(Data source: BASEC)
Patienten in der Dabrafenib & Trametinib Behandlungsgruppe: Dabrafenib wird zweimal pro Tag und Trametinib einmal pro Tag eingenommen.
Patienten in der Chemotherapie Behandlungsgruppe. Die Chemotherapie wird gemäss der lokal üblichen Praxis per Infusion verabreicht (In der Regel wöchentlich, mit Unterbrüchen).
Während der Studienbehandlung wird der Gesundheitszustand der Studienteilnehmer regelmässig kontrolliert. Im ersten Behandlungsjahr wird die Grösse des Tumors mittels bildgebenden Untersuchungen (MRT des Gehirns) alle 8 Wochen gemessen. Danach sind MRT Untersuchungen alle 16 Wochen vorgesehen.
Interventions
(Data source: WHO)
Drug: Dabrafenib;Drug: trametinib;Drug: Carboplatin;Drug: Vincristine
Criteria for participation in trial
(Data source: BASEC)
- Kinder und Jugendliche im Alter zwischen 12 Monaten und 17 Jahren
- Histologisch (durch Analyse des Tumorgewebes unter dem Mikroskop) bestätigte Diagnose eines hochgradigen bzw. tiefgradigen Glioms
- Vorliegen einer sogenannte BRAF V600-Mutation im Tumorgewebe
Exclusion criteria
(Data source: BASEC)
- Vorliegen anderer Krebserkrankungen als ein BRAF-Mutation-positives Gliom
- Vorangehende Behandlung mit Dabrafenib (oder einem anderen RAF-Inhibitor), Trametinib (oder einem anderen MEK-Inhibitor) oder einem ERK-Inhibitor.
-Bei hochgradigem Gliom: Andere Krebstherapien während den 3 vorhergehenden Wochen vor dem Start der Studienbehandlung
-Bei tiefgradigem Gliom: Andere vorausgehende systemische, medikamentöse Krebstherapien
Inclusion/Exclusion Criteria
(Data source: WHO)
Gender: All
Maximum age: 17 Years
Minimum age: 12 Months
Key Inclusion Criteria:
- Diagnosis of BRAF V600 mutant High Grade glioma that had relapsed, progressed or
failed to respond to frontline therapy
- Diagnosis of BRAF V600 mutant Low Grade glioma with progressive disease following
surgical excision, or non-surgical candidates with necessity to begin first systemic
treatment because of a risk of neurological impairment with progression.
- Confirmed measurable disease
Key Exclusion Criteria:
- Previous treatment with dabrafenib, trametinib, other RAF inhibitor, other MEK or ERK
inhibitor
- HGG patient: Cancer treatment within the past 3 weeks. LGG patient: Any systemic
therapy or radiotherapy prior to enrollment
- LGG patients: history of allergic reaction or contraindications to the use of
carboplatin or vincristine
- Stem cell transplant within the past 3 months
- History of heart disease
- Pregnant or lactating females
-
Further information on trial
Recruitment status
Completed
Academic title
(Data source: WHO)
Phase II Open-label Global Study to Evaluate the Effect of Dabrafenib in Combination With Trametinib in Children and Adolescent Patients With BRAF V600 Mutation Positive Low Grade Glioma (LGG) or Relapsed or Refractory High Grade Glioma (HGG)
Type of trial
(Data source: WHO)
Interventional
Design of the trial
(Data source: WHO)
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
Phase
(Data source: WHO)
Phase 2
Primary end point
(Data source: WHO)
LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using Response Assessment in Neuro-Oncology (RANO) Criteria;HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria
Secundary end point
(Data source: WHO)
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension and Trametinib Oral Solution Based on the Palatability Questionnaire Item: Reaction Once the Medication Was Immediately Placed Into the Mouth;HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension and Trametinib Oral Solution Based on the Palatability Questionnaire Item: After Taste Once Rinsing the Mouth With Water Remained;LGG Cohort: Parent Proxy Global Health 7+2 Scores- Global Health Score;LGG Cohort: Parent Proxy Global Health 7+2 Scores- Pain Score;LGG Cohort: Parent Proxy Global Health 7+2 Scores- Fatigue Score;LGG Cohort: ORR by Investigator Assessment Using RANO Criteria;LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria;LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria;LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria;LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Investigator Assessment Using RANO Criteria;LGG Cohort: Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria;LGG Cohort: Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria;LGG Cohort: Clinical Benefit Rate (CBR) by Central Independent Assessment Using RANO Criteria;LGG Cohort: Clinical Benefit Rate (CBR) by Investigator Assessment Using RANO Criteria;LGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS);LGG Cohort: 2-year OS Estimate;HGG Cohort: ORR by Investigator Assessment Using RANO Criteria;HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria;HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria;HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria;HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Investigatort Assessment Using RANO Criteria;HGG Cohort: Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria;HGG Cohort: Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria;HGG Cohort: Clinical Benefit Rate (CBR) as Per Central Independent Assessment Using RANO Criteria;HGG Cohort: Clinical Benefit Rate (CBR) as Per Investigator Assessment Using RANO Criteria;HGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS);AUClast for Trametinib;Cmax for Trametinib;AUCtau for Trametinib;Tmax for Trametinib;T1/2 for Trametinib;Ctrough for Trametinib;AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib);Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib);AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib);Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib);T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib);Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib);HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension and Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth;HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension and Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed
Contact information
(Data source: WHO)
Please refer to primary and secondary sponsors
Trial results
(Data source: WHO)
Results summary
no information available yet
Information on the availability of individual participant data
no information available yet
Trial sites
Trial sites in Switzerland
(Data source: BASEC)
Zurich
Countries
(Data source: WHO)
Argentina, Australia, Belgium, Brazil, Canada, Czechia, Denmark, Finland, France, Germany, Israel, Italy, Japan, Netherlands, Russian Federation, Spain, Sweden, Switzerland, United Kingdom, United States
Contact for further information on the trial
Details of contact in Switzerland
(Data source: BASEC)
Janine Landolt
+41 79 500 93 56
janine.landolt@novartis.com
Contact for general information
(Data source: WHO)
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Contact for scientific information
(Data source: WHO)
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Authorisation by the ethics committee (Data source: BASEC)
Name of the authorising ethics committee (for multicentre studies only the lead committee)
Kantonale
Ethikkommission Zürich
Date of authorisation by the ethics committee
26.10.2017
Further trial identification numbers
Trial identification number of the ethics committee (BASEC-ID)
(Data source: BASEC)
2017-01632
Secondary ID (Data source: WHO)
2015-004015-20
CDRB436G2201
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