Phase 2
N=151
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
Diffuse Astrocytoma · Anaplastic Astrocytoma · Astrocytoma · Oligodendroglioma, Childhood · Anaplastic Oligodendroglioma
Bottom Line
View on ClinicalTrials.gov: NCT02684058 ↗Enrolled (actual)
151
Serious AEs
50.3%
Results posted
May 2023
Primary outcome: Primary: LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using Response Assessment in Neuro-Oncology (RANO) Criteria — 46.6; 10.8 Percentage of participants — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Dabrafenib (Drug); trametinib (Drug); Carboplatin (Drug); Vincristine (Drug)
- Age
- Pediatric · 0+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Aug 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using Response Assessment in Neuro-Oncology (RANO) Criteria |
46.6; 10.8 | <0.001 sig |
| PRIMARY HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria |
56.1 | — |
| SECONDARY LGG Cohort: ORR by Investigator Assessment Using RANO Criteria |
54.8; 13.5; 58.9; 18.9 | — |
| SECONDARY LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria |
20.3; NA; 30.0; 19.4 | — |
| SECONDARY LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria |
NA; NA; 44.4; 22.5 | — |
| SECONDARY LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria |
20.1; 7.4; 24.9; 7.2 | <0.001 sig |
| SECONDARY LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Investigator Assessment Using RANO Criteria |
NA; NA; 46.0; 30.8 | — |
| SECONDARY LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria |
11.0; NA | — |
| SECONDARY LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria |
7.4; NA | — |
| SECONDARY LGG Cohort: Clinical Benefit Rate (CBR) by Central Independent Assessment Using RANO Criteria |
86.3; 43.2 | — |
| SECONDARY LGG Cohort: Clinical Benefit Rate (CBR) by Investigator Assessment Using RANO Criteria |
91.8; 56.8 | — |
| SECONDARY LGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS) |
NA; NA | — |
| SECONDARY LGG Cohort: 2-year OS Estimate |
100.0; 96.9 | — |
| SECONDARY HGG Cohort: ORR by Investigator Assessment Using RANO Criteria |
58.5; 61.0 | — |
| SECONDARY HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria |
22.2; 27.4 | — |
| SECONDARY HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria |
26.6; 32.7 | — |
| SECONDARY HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria |
9.0 | — |
| SECONDARY HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Investigatort Assessment Using RANO Criteria |
24.0 | — |
| SECONDARY HGG Cohort: Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria |
8.5 | — |
| SECONDARY HGG Cohort: Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria |
3.4 | — |
| SECONDARY HGG Cohort: Clinical Benefit Rate (CBR) as Per Central Independent Assessment Using RANO Criteria |
65.9 | — |
| SECONDARY HGG Cohort: Clinical Benefit Rate (CBR) as Per Investigator Assessment Using RANO Criteria |
75.6 | — |
| SECONDARY HGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS) |
NA | — |
| SECONDARY AUClast for Trametinib |
282; 328 | — |
| SECONDARY Cmax for Trametinib |
21.3; 22.7 | — |
| SECONDARY AUCtau for Trametinib |
307; 339 | — |
| SECONDARY Tmax for Trametinib |
1.67; 1.53 | — |
| SECONDARY T1/2 for Trametinib |
26.7; 25.7 | — |
| SECONDARY Ctrough for Trametinib |
8.73; 9.82 | — |
| SECONDARY AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) |
4330; 4870; 73400; 64200; 3520; 3870 | — |
| SECONDARY Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) |
1520; 1330; 9050; 7210; 388; 377 | — |
| SECONDARY AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) |
4300; 4910; 71200; 60700; 3360; 3660 | — |
| SECONDARY Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) |
1.47; 1.47; 3.37; 3.66; 2.21; 2.29 | — |
| SECONDARY T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) |
2.48; 3.09; 7.12; 6.59; 7.06; 16.1 | — |
| SECONDARY Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib) |
38.0; 46.0; 3980; 3190; 275; 310 | — |
| SECONDARY HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth |
5; 18; 2; 4; 0; 0 | — |
| SECONDARY HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth |
2; 15; 3; 5; 0; 2 | — |
| SECONDARY HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed |
4; 13; 1; 6; 0; 0 | — |
| SECONDARY HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed |
3; 15; 3; 5; 0; 2 | — |
| SECONDARY HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth |
4; 13; 1; 5; 0; 1 | — |
| SECONDARY HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth |
3; 15; 3; 4; 0; 3 | — |
| SECONDARY HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water |
4; 15; 2; 5; 0; 0 | — |
| SECONDARY HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water |
2; 15; 2; 3; 0; 2 | — |
| SECONDARY LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score |
42.67; 42.89; 42.14; 39.06; 43.83; 38.36 | — |
| SECONDARY LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score |
52.14; 52.64; 50.11; 50.97; 49.93; 51.00 | — |
| SECONDARY LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score |
53.30; 54.37; 53.96; 56.88; 52.68; 58.10 | — |
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)
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT02684058). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.