Clinical Trials /

Phase II Pediatric Study With Dabrafenib in Combination With Trametinib in Patients With HGG and LGG

NCT02684058

Description:

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.

Related Conditions:
  • Glioma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Pediatric Study With Dabrafenib in Combination With Trametinib in Patients With HGG and LGG
  • Official 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)

Clinical Trial IDs

  • ORG STUDY ID: CDRB436G2201
  • SECONDARY ID: 2015-004015-20
  • NCT ID: NCT02684058

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

DrugSynonymsArms
dabrafenibDRB436HGG cohort: Dabrafenib and trametinib
trametinibTMT212HGG cohort: Dabrafenib and trametinib
Carboplatin with vincristineLGG cohort: Carboplatin with vincristine

Purpose

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 Arms

NameTypeDescriptionInterventions
HGG cohort: Dabrafenib and trametinibExperimentalHGG cohort: All patients in the HGG cohort will receive DRB+TMT
  • dabrafenib
  • trametinib
LGG cohort: Carboplatin with vincristineActive ComparatorLGG cohort: Patients randomized 2:1 to either DRB+TMT or active comparator chemotherapy.
  • Carboplatin with vincristine
LGG cohort: Dabrafenib and trametinibExperimentalLGG cohort: Patients randomized 2:1 to either DRB+TMT or active comparator chemotherapy.
  • dabrafenib
  • trametinib

Eligibility Criteria

        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 whose tumor is unresectable and who
             require treatment

          -  Confirmed measurable disease

        Exclusion Criteria:

          -  Previous treatment with dabrafenib, trametinib, other RAF inhibitor, other MEK or ERK
             inhibitor

          -  Cancer treatment within the past 3 weeks

          -  Stem cell transplant within the past 3 months

          -  History of heart disease

          -  Pregnant or lactating females
      
Maximum Eligible Age:17 Years
Minimum Eligible Age:6 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:HGG cohort: Overall response rate (ORR)
Time Frame:Within the first 32 weeks of treatment
Safety Issue:
Description:HGG cohort: ORR as determined by investigator assessment based on Magnetic resonance imaging MRI) or CT (CAT) scans using Response Assessment in Neuro-Oncology Criteria (RANO) criteria.

Secondary Outcome Measures

Measure:HGG cohort: Overall response rate (ORR)
Time Frame:Within the first 32 weeks of treatment
Safety Issue:
Description:HGG cohort ORR as determined by central independent review based on Magnetic resonance imaging (MRI) or CT (CAT)scans using Response Assessment in Neuro-Oncology (RANO criteria)
Measure:HGG and LGG cohorts: Duration of response (DOR)
Time Frame:Within the first year of treatment
Safety Issue:
Description:HGG and LGG cohorts: DOR as assessed separately by investigator and central review based on MRI or CT scans using RANO criteria
Measure:HGG and LGG cohorts: Time to response (TTR)
Time Frame:Within the first year of treatment
Safety Issue:
Description:HGG and LGG cohorts: TTR as assessed separately by investigator and central review based on MRI or CT scans using RANO criteria
Measure:HGG and LGG cohorts: Overall survival (OS)
Time Frame:2 years from last patient dosed
Safety Issue:
Description:HGG and LGG cohorts: OS as defined as the time from first dose to death due to any cause
Measure:HGG and LGG cohorts: Progression free survival (PFS)
Time Frame:Within 4 months of treatment
Safety Issue:
Description:HGG and LGG cohorts: PFS as assessed separately by investigator and central review based on MRI or CT scans using RANO criteria
Measure:Patients on DRB+TMT: Area under the curve (AUClast)
Time Frame:Within the first month of treatment
Safety Issue:
Description:Patients on DRB+TMT: Assessed from time zero to the last measurable sampling time
Measure:Patients on DRB+TMT: Area under the curve (AUCtau)
Time Frame:Within the first month of treatment
Safety Issue:
Description:Patients on DRB+TMT: Calculated to the end of a dosing interval at steady state (12 hours)
Measure:Patients on DRB+TMT: Maximum Plasma Concentration (Cmax)
Time Frame:Within the first month of treatment
Safety Issue:
Description:Patients on DRB+TMT: The maximum (peak) observed plasma drug concentration after a single dose
Measure:Patients on DRB+TMT: Time to reach maximum concentration (Tmax)
Time Frame:Within the first month of treatment
Safety Issue:
Description:Patients on DRB+TMT: The time to reach maximum (peak) concentration of study drug after a single dose
Measure:Patients on DRB+TMT: Elimination half-life (T1/2)
Time Frame:Within the first month of treatment
Safety Issue:
Description:Patients on DRB+TMT: The elimination half-life associated with the terminal slope of a semi-log concentration-time curve
Measure:Patients on DRB+TMT: Predose plasma concentration (Ctrough)
Time Frame:Within the first month of treatment
Safety Issue:
Description:Patients on DRB+TMT: Measured concentration at the end of a dosing interval at steady state, taken directly before next study drug administration).
Measure:HGG and LGG cohorts: Adverse events
Time Frame:From first dose to end of treatment (EOT)
Safety Issue:
Description: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
Measure:HGG and LGG cohorts: Vital signs
Time Frame:First dose to end of treatment
Safety Issue:
Description: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.
Measure:HGG and LGG cohorts: Abnormal lab values
Time Frame:First dose to end of treatment
Safety Issue:
Description: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
Measure:HGG and LGG cohorts: Changes in Electrocardiogram (ECG)
Time Frame:First dose to end of treatment
Safety Issue:
Description: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
Measure:HGG and LGG cohorts: ECHO
Time Frame:First dose to end of treatment
Safety Issue:
Description: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.
Measure:LGG cohort: Overall response rate (ORR)
Time Frame:Within the first 32 weeks of treatment
Safety Issue:
Description:LGG cohort: ORR as determined by investigator assessment based on MRI or CT scans using RANO criteria
Measure:HGG and LGG cohort: Palatability of pediatric formulations
Time Frame:Within the first 5 weeks of treatment
Safety Issue:
Description:HGG and LGG cohort: Palatability questionnaire data for DRB suspension and TMT solution
Measure:LGG cohort: PROMIS Parent Proxy scale
Time Frame:Within the first 32 weeks of treatment
Safety Issue:
Description:LGG cohort only: PROMIS parent proxy scale to estimate differences between treatment groups
Measure:HGG and LGG Cohorts: Clinical benefit rate (CBR)
Time Frame:Within the first 24 weeks of treatment
Safety Issue:
Description:HGG and LGG cohorts: CBR as assessed separately by investigator and central review of MRI and CT scans per RANO criteria
Measure:LGG cohort: 2 year Overall survival (OS)
Time Frame:2 years from first dose
Safety Issue:
Description:LGG cohort: OS as defined as the time from the first dose to death due to any cause

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Malignant glioma
  • BRAF mutant positive
  • High grade glioma
  • Low grade glioma
  • Dabrafenib
  • Trametinib
  • Pediatrics
  • Brain neoplasma

Last Updated

March 8, 2018