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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.

Register:	ClinicalTrials.gov
Last refreshed on:	29 May 2023
Main ID:	NCT02684058
Date of registration:	04/02/2016
Prospective Registration:	Yes
Primary sponsor:	Novartis Pharmaceuticals
Public title:	Study of Efficacy and Safety of Dabrafenib in Combination With Trametinib in Pediatric Patients With BRAF V600 Mutation Positive LGG or Relapsed or Refractory HGG Tumors
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)
Date of first enrolment:	December 28, 2017
Target sample size:	151
Recruitment status:	Completed
URL:	https://clinicaltrials.gov/show/NCT02684058
Study type:	Interventional
Study design:	Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
Phase:	Phase 2

Countries of recruitment
Argentina	Australia	Belgium	Brazil	Canada	Czechia	Denmark	Finland
France	Germany	Israel	Italy	Japan	Netherlands	Russian Federation	Spain
Sweden	Switzerland	United Kingdom	United States

Contacts

Name:	Novartis Pharmaceuticals
Address:
Telephone:
Email:
Affiliation:	Novartis Pharmaceuticals

Key inclusion & exclusion criteria

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

Age minimum: 12 Months
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Angiocentric Glioma

Diffuse Astrocytoma

Anaplastic Ganglioglioma

Anaplastic Oligodendroglioma

Anaplastic Astrocytoma

Papillary Glioneuronal Tumor

Pilocytic Astrocytoma

Anaplastic Pleomorphic Xanthoastrocytoma

Extraventricular Neurocytoma

Central Neurocytoma

Oligodendroglioma, Childhood

Rosette-forming Glioneurona Tumor

Cerebellar Iponeurocytoma

Giant Cell Astrocytoma

Gangliocytoma

Ganglioglioma

Astrocytoma

Chordoid Glioma of Third Ventricle

Desmoplastic Infantile Astrocytoma and Ganglioglioma

Dysplastic Gangliocytoma of Cerebrellum

Glioblastoma

Pleomorphic Xanthoastrocytoma

Intervention(s)

Drug: Carboplatin

Drug: Dabrafenib

Drug: trametinib

Drug: Vincristine

Primary Outcome(s)

HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria [Time Frame: Up to approximately 3.2 years]

LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using Response Assessment in Neuro-Oncology (RANO) Criteria [Time Frame: Up to approximately 3 years]

Secondary Outcome(s)

AUClast for Trametinib [Time Frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose]

Cmax for Trametinib [Time Frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose]

Ctrough for Trametinib [Time Frame: Week 3 Day 1 pre-dose]

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 [Time Frame: Week 1 and Week 5]

HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria [Time Frame: Up to approximately 3.2 years]

LGG Cohort: Parent Proxy Global Health 7+2 Scores- Fatigue Score [Time Frame: Up to approximately 5 years]

LGG Cohort: Parent Proxy Global Health 7+2 Scores- Pain Score [Time Frame: Up to approximately 5 years]

AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) [Time Frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose]

Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) [Time Frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose]

AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) [Time Frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose]

HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria [Time Frame: Up to approximately 3.2 years]

HGG Cohort: Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria [Time Frame: Up to approximately 5 years]

HGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS) [Time Frame: Up to approximately 5 years]

LGG Cohort: 2-year OS Estimate [Time Frame: 2 years from first dose]

Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) [Time Frame: Week 3 Day 1 pre-dose]

HGG Cohort: Clinical Benefit Rate (CBR) as Per Investigator Assessment Using RANO Criteria [Time Frame: Up to approximately 5 years]

T1/2 for Trametinib [Time Frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose]

LGG Cohort: Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria [Time Frame: Up to approximately 5 years]

HGG Cohort: Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria [Time Frame: Up to approximately 5 years]

AUCtau for Trametinib [Time Frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose]

LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria [Time Frame: Up to approximately 3 years]

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 [Time Frame: Week 1 and Week 5]

LGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS) [Time Frame: Up to approximately 5 years]

T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) [Time Frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose]

LGG Cohort: Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria [Time Frame: Up to approximately 5 years]

HGG Cohort: Clinical Benefit Rate (CBR) as Per Central Independent Assessment Using RANO Criteria [Time Frame: Up to approximately 5 years]

HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Investigatort Assessment Using RANO Criteria [Time Frame: Up to approximately 5 years]

HGG Cohort: ORR by Investigator Assessment Using RANO Criteria [Time Frame: Up to approximately 3.2 years]

Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) [Time Frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose]

Tmax for Trametinib [Time Frame: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose]

LGG Cohort: Clinical Benefit Rate (CBR) by Central Independent Assessment Using RANO Criteria [Time Frame: Up to approximately 5 years]

LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria [Time Frame: Up to approximately 3 years]

LGG Cohort: Clinical Benefit Rate (CBR) by Investigator Assessment Using RANO Criteria [Time Frame: Up to approximately 5 years]

LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria [Time Frame: Up to approximately 3 years]

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 [Time Frame: Week 1 and Week 5]

LGG Cohort: ORR by Investigator Assessment Using RANO Criteria [Time Frame: Up to approximately 3 years]

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 [Time Frame: Week 1 and Week 5]

HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria [Time Frame: Up to approximately 5 years]

LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Investigator Assessment Using RANO Criteria [Time Frame: Up to approximately 3 years]

LGG Cohort: Parent Proxy Global Health 7+2 Scores- Global Health Score [Time Frame: Up to approximately 5 years]

Secondary ID(s)

CDRB436G2201

2015-004015-20

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Ethics review

Results

Results available:	Yes
Date Posted:	19/05/2023
Date Completed:
URL:	https://clinicaltrials.gov/ct2/show/results/NCT02684058

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