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.
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
| Drug | Synonyms | Arms |
|---|
| dabrafenib | DRB436 | HGG cohort: Dabrafenib and trametinib |
| trametinib | TMT212 | HGG cohort: Dabrafenib and trametinib |
| Carboplatin with vincristine | | LGG 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
| Name | Type | Description | Interventions |
|---|
| HGG cohort: Dabrafenib and trametinib | Experimental | HGG cohort: All patients in the HGG cohort will receive DRB+TMT | |
| LGG cohort: Carboplatin with vincristine | Active Comparator | LGG cohort: Patients randomized 2:1 to either DRB+TMT or active comparator chemotherapy. | - Carboplatin with vincristine
|
| LGG cohort: Dabrafenib and trametinib | Experimental | LGG cohort: Patients randomized 2:1 to either DRB+TMT or active comparator chemotherapy. | |
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 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
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.
| Maximum Eligible Age: | 17 Years |
| Minimum Eligible Age: | 12 Months |
| 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 central independent 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 investigator assessment 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: | Active, not 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
April 8, 2021
