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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02684058




Registration number
NCT02684058
Ethics application status
Date submitted
4/02/2016
Date registered
17/02/2016
Date last updated
15/04/2020

Titles & IDs
Public title
Phase II Pediatric Study With Dabrafenib in Combination With Trametinib in Patients With HGG and LGG
Scientific title
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)
Secondary ID [1] 0 0
2015-004015-20
Secondary ID [2] 0 0
CDRB436G2201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diffuse Astrocytoma 0 0
Anaplastic Astrocytoma 0 0
Astrocytoma 0 0
Oligodendroglioma, Childhood 0 0
Anaplastic Oligodendroglioma 0 0
Glioblastoma 0 0
Pilocytic Astrocytoma 0 0
Giant Cell Astrocytoma 0 0
Pleomorphic Xanthoastrocytoma 0 0
Anaplastic Pleomorphic Xanthoastrocytoma 0 0
Angiocentric Glioma 0 0
Chordoid Glioma of Third Ventricle 0 0
Gangliocytoma 0 0
Ganglioglioma 0 0
Anaplastic Ganglioglioma 0 0
Dysplastic Gangliocytoma of Cerebrellum 0 0
Desmoplastic Infantile Astrocytoma and Ganglioglioma 0 0
Papillary Glioneuronal Tumor 0 0
Rosette-forming Glioneurona Tumor 0 0
Central Neurocytoma 0 0
Extraventricular Neurocytoma 0 0
Cerebellar Iponeurocytoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - dabrafenib
Treatment: Drugs - trametinib
Treatment: Drugs - Carboplatin with vincristine

Experimental: HGG cohort: Dabrafenib and trametinib - HGG cohort: All patients in the HGG cohort will receive DRB+TMT

Active Comparator: LGG cohort: Carboplatin with vincristine - LGG cohort: Patients randomized 2:1 to either DRB+TMT or active comparator chemotherapy.

Experimental: LGG cohort: Dabrafenib and trametinib - LGG cohort: Patients randomized 2:1 to either DRB+TMT or active comparator chemotherapy.


Treatment: Drugs: dabrafenib
dabrafenib oral, twice daily.

Treatment: Drugs: trametinib
trametinib oral, once daily.

Treatment: Drugs: Carboplatin with vincristine
Chemotherapy of carboplatin with vincristine - LGG only

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
HGG cohort: Overall response rate (ORR) - HGG cohort: ORR as determined by central independent assessment based on Magnetic resonance imaging MRI) or CT (CAT) scans using Response Assessment in Neuro-Oncology Criteria (RANO) criteria.
Timepoint [1] 0 0
Within the first 32 weeks of treatment
Primary outcome [2] 0 0
LGG cohort: Overall response rate (ORR) - LGG cohort: ORR as determined by blinded central independent assessment based on MRI or CT scans using RANO criteria.
Timepoint [2] 0 0
Within the first 32 weeks of treatment
Secondary outcome [1] 0 0
HGG cohort: Overall response rate (ORR) - HGG cohort ORR as determined by investigator assessment based on Magnetic resonance imaging (MRI) or CT (CAT)scans using Response Assessment in Neuro-Oncology (RANO criteria)
Timepoint [1] 0 0
Within the first 32 weeks of treatment
Secondary outcome [2] 0 0
HGG and LGG cohorts: Duration of response (DOR) - HGG and LGG cohorts: DOR as assessed separately by investigator and central review based on MRI or CT scans using RANO criteria
Timepoint [2] 0 0
Within the first year of treatment
Secondary outcome [3] 0 0
HGG and LGG cohorts: Time to response (TTR) - HGG and LGG cohorts: TTR as assessed separately by investigator and central review based on MRI or CT scans using RANO criteria
Timepoint [3] 0 0
Within the first year of treatment
Secondary outcome [4] 0 0
HGG and LGG cohorts: Overall survival (OS) - HGG and LGG cohorts: OS as defined as the time from first dose to death due to any cause
Timepoint [4] 0 0
2 years from last patient dosed
Secondary outcome [5] 0 0
HGG and LGG cohorts: Progression free survival (PFS) - HGG and LGG cohorts: PFS as assessed separately by investigator and central review based on MRI or CT scans using RANO criteria
Timepoint [5] 0 0
Within 4 months of treatment
Secondary outcome [6] 0 0
Patients on DRB+TMT: Area under the curve (AUClast) - Patients on DRB+TMT: Assessed from time zero to the last measurable sampling time
Timepoint [6] 0 0
Within the first month of treatment
Secondary outcome [7] 0 0
Patients on DRB+TMT: Area under the curve (AUCtau) - Patients on DRB+TMT: Calculated to the end of a dosing interval at steady state (12 hours)
Timepoint [7] 0 0
Within the first month of treatment
Secondary outcome [8] 0 0
Patients on DRB+TMT: Maximum Plasma Concentration (Cmax) - Patients on DRB+TMT: The maximum (peak) observed plasma drug concentration after a single dose
Timepoint [8] 0 0
Within the first month of treatment
Secondary outcome [9] 0 0
Patients on DRB+TMT: Time to reach maximum concentration (Tmax) - Patients on DRB+TMT: The time to reach maximum (peak) concentration of study drug after a single dose
Timepoint [9] 0 0
Within the first month of treatment
Secondary outcome [10] 0 0
Patients on DRB+TMT: Elimination half-life (T1/2) - Patients on DRB+TMT: The elimination half-life associated with the terminal slope of a semi-log concentration-time curve
Timepoint [10] 0 0
Within the first month of treatment
Secondary outcome [11] 0 0
Patients on DRB+TMT: Predose plasma concentration (Ctrough) - Patients on DRB+TMT: Measured concentration at the end of a dosing interval at steady state, taken directly before next study drug administration).
Timepoint [11] 0 0
Within the first month of treatment
Secondary outcome [12] 0 0
HGG and LGG cohorts: Adverse events - HGG cohort: Incidence of AEs and SAEs reported during treatment with dabrafenib and trametinib in this population. LGG cohort: Incidence of AEs and SAEs reported during treatment with dabrafenib and trametinib as compared to chemotherapy
Timepoint [12] 0 0
From first dose to end of treatment (EOT)
Secondary outcome [13] 0 0
HGG and LGG cohorts: Vital signs - HGG: Assess the safety of dabrafenib and trametinib in this population through monitoring changes in vital signs. LGG: Assess the safety of dabrafenib and trametinib in this population as compared to chemotherapy through monitoring changes in vital signs.
Timepoint [13] 0 0
First dose to end of treatment
Secondary outcome [14] 0 0
HGG and LGG cohorts: Abnormal lab values - HGG: Assess the safety of dabrafenib and trametinib in this population through hematology, chemistry and urinalysis tests. LGG: Assess the safety of dabrafenib and trametinib in this population as compared to chemotherapy through hematology, chemistry and urinalysis tests
Timepoint [14] 0 0
First dose to end of treatment
Secondary outcome [15] 0 0
HGG and LGG cohorts: Changes in Electrocardiogram (ECG) - HGG: Assess the safety of dabrafenib and trametinib in this population through changes in ECG values. LGG: Assess the safety of dabrafenib and trametinib as compared to chemotherapy in this population through changes in ECG values
Timepoint [15] 0 0
First dose to end of treatment
Secondary outcome [16] 0 0
HGG and LGG cohorts: ECHO - HGG: Assess the safety of dabrafenib and trametinib in this patient population through changes in ECHO results. LGG: Assess the safety of dabrafenib and trametinib in this patient population as compared to chemotherapy through changes in ECHO results.
Timepoint [16] 0 0
First dose to end of treatment
Secondary outcome [17] 0 0
LGG cohort: Overall response rate (ORR) - LGG cohort: ORR as determined by investigator assessment based on MRI or CT scans using RANO criteria
Timepoint [17] 0 0
Within the first 32 weeks of treatment
Secondary outcome [18] 0 0
HGG and LGG cohort: Palatability of pediatric formulations - HGG and LGG cohort: Palatability questionnaire data for DRB suspension and TMT solution
Timepoint [18] 0 0
Within the first 5 weeks of treatment
Secondary outcome [19] 0 0
LGG cohort: PROMIS Parent Proxy scale - LGG cohort only: PROMIS parent proxy scale to estimate differences between treatment groups
Timepoint [19] 0 0
Within the first 32 weeks of treatment
Secondary outcome [20] 0 0
HGG and LGG Cohorts: Clinical benefit rate (CBR) - HGG and LGG cohorts: CBR as assessed separately by investigator and central review of MRI and CT scans per RANO criteria
Timepoint [20] 0 0
Within the first 24 weeks of treatment
Secondary outcome [21] 0 0
LGG cohort: 2 year Overall survival (OS) - LGG cohort: OS as defined as the time from the first dose to death due to any cause
Timepoint [21] 0 0
2 years from first dose

Eligibility
Key inclusion criteria
- Diagnosis of BRAF V600 mutant High Grade glioma that has 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
Minimum age
12 Months
Maximum age
17 Years
Gender
Both males and females
Can healthy volunteers participate?
No
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

Other protocol-defined Inclusion/exclusion may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Randwick
Recruitment hospital [2] 0 0
Novartis Investigative Site - Parkville
Recruitment postcode(s) [1] 0 0
2130 - Randwick
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
Argentina
State/province [16] 0 0
Buenos Aires
Country [17] 0 0
Belgium
State/province [17] 0 0
Brussels
Country [18] 0 0
Belgium
State/province [18] 0 0
Leuven
Country [19] 0 0
Brazil
State/province [19] 0 0
SP
Country [20] 0 0
Canada
State/province [20] 0 0
British Colombia
Country [21] 0 0
Canada
State/province [21] 0 0
Ontario
Country [22] 0 0
Canada
State/province [22] 0 0
Quebec
Country [23] 0 0
Czechia
State/province [23] 0 0
Brno
Country [24] 0 0
Czechia
State/province [24] 0 0
Praha 5
Country [25] 0 0
Denmark
State/province [25] 0 0
Copenhagen
Country [26] 0 0
Finland
State/province [26] 0 0
Tampere
Country [27] 0 0
France
State/province [27] 0 0
Angers Cedex 1
Country [28] 0 0
France
State/province [28] 0 0
Lille Cedex
Country [29] 0 0
France
State/province [29] 0 0
Lyon Cedex
Country [30] 0 0
France
State/province [30] 0 0
Marseille Cedex 5
Country [31] 0 0
France
State/province [31] 0 0
Paris
Country [32] 0 0
France
State/province [32] 0 0
Strasbourg Cedex
Country [33] 0 0
France
State/province [33] 0 0
Toulouse Cedex 9
Country [34] 0 0
France
State/province [34] 0 0
Villejuif Cedex
Country [35] 0 0
Germany
State/province [35] 0 0
Augsburg
Country [36] 0 0
Germany
State/province [36] 0 0
Berlin
Country [37] 0 0
Germany
State/province [37] 0 0
Essen
Country [38] 0 0
Germany
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Gottingen
Country [39] 0 0
Germany
State/province [39] 0 0
Hamburg
Country [40] 0 0
Germany
State/province [40] 0 0
Heidelberg
Country [41] 0 0
Germany
State/province [41] 0 0
Koeln
Country [42] 0 0
Israel
State/province [42] 0 0
Tel-Hashomer
Country [43] 0 0
Italy
State/province [43] 0 0
GE
Country [44] 0 0
Italy
State/province [44] 0 0
MI
Country [45] 0 0
Italy
State/province [45] 0 0
RM
Country [46] 0 0
Italy
State/province [46] 0 0
TO
Country [47] 0 0
Japan
State/province [47] 0 0
Fukuoka
Country [48] 0 0
Japan
State/province [48] 0 0
Tokyo
Country [49] 0 0
Japan
State/province [49] 0 0
Osaka
Country [50] 0 0
Netherlands
State/province [50] 0 0
CS
Country [51] 0 0
Netherlands
State/province [51] 0 0
Rotterdam
Country [52] 0 0
Russian Federation
State/province [52] 0 0
Moscow
Country [53] 0 0
Spain
State/province [53] 0 0
Andalucia
Country [54] 0 0
Spain
State/province [54] 0 0
Catalunya
Country [55] 0 0
Spain
State/province [55] 0 0
Madrid
Country [56] 0 0
Spain
State/province [56] 0 0
Valencia
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Sweden
State/province [57] 0 0
Stockholm
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Switzerland
State/province [58] 0 0
Zuerich
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Leeds
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Liverpool
Country [61] 0 0
United Kingdom
State/province [61] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to investigate the activity of dabrafenib in combination with
trametinib in children and adolescent patients with BRAF V600 mutation positive low grade
glioma or relapsed or refractory high grade glioma.
Trial website
https://clinicaltrials.gov/show/NCT02684058
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
novartis.email@novartis.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02684058