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

Summary

The purpose of this study was to investigate the activity 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)

Conditions

• 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

Interventions

DRUG

Dabrafenib

Dabrafenib was available as 50 mg and 75 mg hard capsules and as 10 mg dispersible tablets for oral suspension. Dabrafenib was administered orally, twice daily, and was dosed based on age and weight Patients \< 12 years old and ≥ 16 kg were to be administered either the dabrafenib capsules or dabrafenib dispersible tablets for oral suspension (dose: 5.25 mg/kg/day) Patients ≥ 12 years old and ≥ 19 kg were to be administered either the dabrafenib capsules or dabrafenib dispersible tablets for oral suspension (dose: 4.5 mg/kg/day) Patients \< 12 years old and \< 16 kg were to be administered dabrafenib dispersible tablets for oral suspension (dose: 5.25 mg/kg/day) Patients ≥12 years old and \<19 kg were to be administered dabrafenib dispersible tablets for oral suspension (dose: 4.5 mg/kg/day)

DRUG

trametinib

Trametinib was available as 0.5 mg and 2 mg film-coated tablets and as 5.0 mg powder in bottle for oral solution (0.05 mg/ml after reconstitution with 90 ml water).Trametinib was administered orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on age and weight. Patients \<6 years old and \<26 kg were to be administered the trametinib oral solution (dose: 0.032 mg/kg/day) Patients \<6 years old and ≥26 kg were to be administered either the trametinib oral solution or trametinib tablets (dose: 0.032 mg/kg/day) Patients ≥6 years old and ≥10 kg \< 33 kg were to be administered the trametinib oral solution (dose: 0.025 mg/kg/day) Patients ≥6 years old and ≥33 kg were to be administered either the trametinib oral solution or the trametinib tablets (dose: 0.025 mg/kg/day)

DRUG

Carboplatin

Carboplatin was supplied locally as commercially available and labelled accordingly to comply with legal requirements of each country. Carboplatin was administered as one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Each maintenance cycle was 6 weeks, and consisted of 4 weeks of chemotherapy with 2 weeks of rest. Induction: 175 mg/m\^2 as weekly intravenous (IV) infusion on weeks 1 to 4, and on weeks 7 to 10, on the same day as vincristine dosing Maintenance: 175 mg/m\^2 as weekly IV infusion over 60 minutes on weeks 1 to 4 of each cycle.

DRUG

Vincristine

Vincristine was supplied locally as commercially available and labelled accordingly to comply with legal requirements of each country. Vincristine was administered as one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy. Induction: 1.5 mg/m\^2 as weekly IV bolus infusion (0.05 mg/kg if child is \<12 kg) (maximum dose of 2.0 mg) for 10 weeks. Maintenance: 1.5 mg/m\^2 as weekly IV bolus infusion (0.05 mg/kg if child is \<12 kg) (maximum dose of 2.0 mg) on weeks 1 to 3 of each cycle, on the same day as carboplatin dosing.

Sponsors & Collaborators

• Novartis Pharmaceuticals

  lead INDUSTRY

Principal Investigators

• Novartis Pharmaceuticals · Novartis Pharmaceuticals

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

12 Months

Max Age

17 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-12-28

Primary Completion

2021-08-23

Completion

2023-04-28

FDA Drug

Yes

Countries

• United States
• Argentina
• Australia
• Belgium
• Brazil
• Canada
• Czechia
• Denmark
• Finland
• France
• Germany
• Israel
• Italy
• Japan
• Netherlands
• Russia
• Spain
• Sweden
• Switzerland
• United Kingdom

Study Locations