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

Conditions

• Anaplastic Astrocytoma
• Anaplastic Ganglioglioma
• Anaplastic Oligodendroglioma
• Anaplastic Pleomorphic Xanthoastrocytoma
• Angiocentric Glioma
• Astrocytoma
• Central Neurocytoma
• Cerebellar Iponeurocytoma
• Chordoid Glioma of Third Ventricle
• Desmoplastic Infantile Astrocytoma and Ganglioglioma
• Diffuse Astrocytoma
• Dysplastic Gangliocytoma of Cerebrellum
• Extraventricular Neurocytoma
• Gangliocytoma
• Ganglioglioma
• Giant Cell Astrocytoma
• Glioblastoma
• Oligodendroglioma, Childhood
• Papillary Glioneuronal Tumor
• Pilocytic Astrocytoma
• Pleomorphic Xanthoastrocytoma
• Rosette-forming Glioneurona Tumor

Eligibility Criteria

Sex

ALL

Age

12 Months - 17 Years

Healthy Volunteers

Not accepted

Interventions

• Dabrafenib — DRUG
  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)
• trametinib — DRUG
  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)
• Carboplatin — DRUG
  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.
• Vincristine — DRUG
  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.

Study Details

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)

Key Dates

Start date

Dec 28, 2017

Status verified

Nov 2023

Primary completion

Aug 23, 2021

Completion

Apr 28, 2023

Study Design

Enrollment

151 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: LGG cohort: dabrafenib and trametinib
  Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)
• Active Comparator: LGG cohort: carboplatin and vincristine
  Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy.
• Experimental: HGG cohort: dabrafenib and trametinib
  Participants in the HGG cohort received dabrafenib (orally, twice daily and dosed based on weight and age) and trametinib (orally, once daily in combination with the first daily dose of dabrafenib and dosed based on weight)

Primary Outcome Measure

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

Locations (10)

Find similar trials in Orange, CA

Related Studies

• INdividualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT)
  PHASE2 · Recruiting · Patrick Wen, MD · Birmingham, Alabama
• SYNERGY-AI: Artificial Intelligence Based Precision Oncology Clinical Trial Matching and Registry
  Recruiting · Massive Bio, Inc. · Birmingham, Alabama
• HSV-tk and XRT and Chemotherapy for Newly Diagnosed GBM
  PHASE1/PHASE2 · Recruiting · The Methodist Hospital Research Institute · Houston, Texas
• HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors
  PHASE1 · Recruiting · M.D. Anderson Cancer Center · Birmingham, Alabama