TriangleNCT02684058 · CITED IN SOURCE DOCUMENTS
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
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2023-12-13
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)
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using Response Assessment in Neuro-Oncology (RANO) Criteria
HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria
LGG Cohort: ORR by Investigator Assessment Using RANO Criteria
LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria
LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria
LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria
LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Investigator Assessment Using RANO Criteria
LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria
LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria
LGG Cohort: Clinical Benefit Rate (CBR) by Central Independent Assessment Using RANO Criteria
LGG Cohort: Clinical Benefit Rate (CBR) by Investigator Assessment Using RANO Criteria
LGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS)
LGG Cohort: 2-year OS Estimate
HGG Cohort: ORR by Investigator Assessment Using RANO Criteria
HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria
HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria
HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria
HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Investigatort Assessment Using RANO Criteria
HGG Cohort: Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria
HGG Cohort: Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria
HGG Cohort: Clinical Benefit Rate (CBR) as Per Central Independent Assessment Using RANO Criteria
HGG Cohort: Clinical Benefit Rate (CBR) as Per Investigator Assessment Using RANO Criteria
HGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS)
AUClast for Trametinib
Cmax for Trametinib
AUCtau for Trametinib
Tmax for Trametinib
T1/2 for Trametinib
Ctrough for Trametinib
AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)
Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)
AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)
Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)
T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)
Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed
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
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth
HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water
HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score
LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score
All-collected Deaths
LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria (Longer Follow-up Time)
HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria (Longer Follow-up Time)
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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
- healthy Volunteers
- false
- maximum Age
- 17 Years
- minimum Age
- 12 Months
- sex
- ALL
- std Ages
- CHILD
Treatment arms and interventions
- arm Groups
- description
- 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)
- intervention Names
- Drug: Dabrafenib
- Drug: trametinib
- label
- LGG cohort: dabrafenib and trametinib
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Carboplatin
- Drug: Vincristine
- label
- LGG cohort: carboplatin and vincristine
- type
- ACTIVE_COMPARATOR
- description
- 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)
- intervention Names
- Drug: Dabrafenib
- Drug: trametinib
- label
- HGG cohort: dabrafenib and trametinib
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- HGG cohort: dabrafenib and trametinib
- LGG cohort: dabrafenib and trametinib
- description
- 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)
- name
- Dabrafenib
- other Names
- DRB436
- type
- DRUG
- arm Group Labels
- HGG cohort: dabrafenib and trametinib
- LGG cohort: dabrafenib and trametinib
- description
- 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)
- name
- trametinib
- other Names
- TMT212
- type
- DRUG
- arm Group Labels
- LGG cohort: carboplatin and vincristine
- description
- 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.
- name
- Carboplatin
- type
- DRUG
- arm Group Labels
- LGG cohort: carboplatin and vincristine
- description
- 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.
- name
- Vincristine
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 151
- type
- ACTUAL
Registered outcome plans (not posted results)
- other Outcomes
- description
- Percentage of participants with a best overall confirmed CR or PR as assessed per RANO criteria by central independent assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. This analysis was conducted at the end of the trial (after the primary endpoint analysis cut-off date) and includes a longer follow-up time
- measure
- LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria (Longer Follow-up Time)
- time Frame
- Up to approx 4.2 years
- description
- Percentage of participants with a best overall confirmed CR or PR as assessed per RANO criteria by central independent assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. This analysis was conducted at the end of the trial (after the primary endpoint analysis cut-off date) and includes a longer follow-up time
- measure
- HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria (Longer Follow-up Time)
- time Frame
- Up to approx 4.8 years
- primary Outcomes
- description
- Percentage of participants in the LGG cohort with a best overall confirmed Complete Response (CR) or Partial Response (PR) as assessed per RANO criteria by central independent assessment. The 95% confidence intervals (CIs) were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
- 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
- description
- Percentage of participants in the HGG cohort with a best overall confirmed CR or PR as assessed per RANO criteria by central independent assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
- measure
- HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria
- time Frame
- Up to approx. 3.2 years
- secondary Outcomes
- description
- Percentage of participants in the LGG cohort with a best overall confirmed CR or PR as assessed per RANO criteria by investigator assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
- measure
- LGG Cohort: ORR by Investigator Assessment Using RANO Criteria
- time Frame
- Up to approx. 3 years and up to approx 4.2 years
- description
- Time from first documented response (PR or CR) until disease progression or death as per RANO criteria. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy, were censored at the date of the last adequate tumor evaluation. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
- measure
- LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria
- time Frame
- Up to approx. 3 years and up to approx 4.2 years
- description
- Time from first documented response (PR or CR) until disease progression or death as per RANO criteria. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy, were censored at the date of the last adequate tumor evaluation. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
- measure
- LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria
- time Frame
- Up to approx. 3 years and up to approx 4.2 years
- description
- Time from the date of randomization to the date of first documented disease progression as per central independent review assessment using RANO criteria or death due to any cause. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation.
- measure
- LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria
- time Frame
- Up to approx. 3 years and up to approx 4.2 years
- description
- Time from the date of randomization to the date of first documented disease progression as per investigator assessment using RANO criteria or death due to any cause. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation.
- measure
- LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Investigator Assessment Using RANO Criteria
- time Frame
- Up to approx. 3 years and up to approx 4.2 years
- description
- Time from randomization to first documented response of CR or PR as per central independent assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients without an event were censored either at the maximum follow-up time (if they experienced disease progression or death), or at their last tumor assessment date. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
- measure
- LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria
- time Frame
- Up to approx. 4.2 years
- description
- Time from randomization to first documented response of CR or PR as per investigator assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients without an event were censored either at the maximum follow-up time (if they experienced disease progression or death), or at their last tumor assessment date. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
- measure
- LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria
- time Frame
- Up to approx. 4.2 years
- description
- Percentage of participants with a best overall response of CR or PR, or stable disease (SD) which lasts for 24 weeks or longer. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. SD: Partient did not qualify for CR, PR, or progressive disease and has stable nonenhancing (T2/FLAIR) lesions on same or lower doses of corticosteroids compared with baseline scan and clinically stable status.
- measure
- LGG Cohort: Clinical Benefit Rate (CBR) by Central Independent Assessment Using RANO Criteria
- time Frame
- Up to approx. 4.2 years
- description
- Percentage of participants with a best overall response of CR or PR, or stable disease (SD) which lasts for 24 weeks or longer. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. SD: Partient did not qualify for CR, PR, or progressive disease and has stable nonenhancing (T2/FLAIR) lesions on same or lower doses of corticosteroids compared with baseline scan and clinically stable status.
- measure
- LGG Cohort: Clinical Benefit Rate (CBR) by Investigator Assessment Using RANO Criteria
- time Frame
- Up to approx. 4.2 years
- description
- Time from first dose to death due to any cause in the LGG cohort. Confidence Intervals were estimated using the Brookmeyer Crowley method. If a patient was not known to have died at the time of analysis cut-off, OS was censored at the date of last contact.
- measure
- LGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS)
- time Frame
- Up to 4.6 years
- description
- OS was defined as the time from the first dose to death due to any cause in the LGG cohort. The 2-year Kaplan-Meier OS estimate represented the estimated percentage of participants remaining free from OS events for up to 2 years. If a patient was not known to have died at the time of analysis cut-off, OS was censored at the date of last contact
- measure
- LGG Cohort: 2-year OS Estimate
- time Frame
- 2 years from first dose
- description
- ORR in the HGG cohort defined as the percentage of participants in the HGG cohort with a best overall confirmed CR or PR as assessed per RANO criteria by investigator assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.
- measure
- HGG Cohort: ORR by Investigator Assessment Using RANO Criteria
- time Frame
- Up to approx. 3.2 years and up to approx. 4.8 years
Full study description
- brief 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)
- detailed Description
- This study combines two pediatric glioma cohorts (LGG and HGG cohorts) into a multi-center, open-label, Phase II study: * The LGG cohort is a multi-center, randomized, open-label part of this Phase II study conducted in children and adolescent patients with BRAF V600 mutation-positive LGG whose tumor was unresectable and who required first systemic treatment. Participants in the LGG cohort were randomized in a 2:1 ratio to either dabrafenib plus trametinib or carboplatin with vincristine. * The HGG cohort is a multi-center, single-arm, open-label part of this Phase II study conducted in children and adolescent patients with BRAF V600 mutation-positive, refractory or relapsed HGG tumors after having received at least one previous standard therapy. The duration of treatment for participants on dabrafenib plus trametinib in LGG and for all patients in the HGG cohort was continued until the loss of clinical benefit in the opinion of the Investigator, unacceptable toxicity, start of a new anti-neoplastic therapy, discontinuation at the discretion of the investigator or patient/legal guardian, lost to follow-up, death, study termination by the sponsor, or until disease progression. The duration of treatment for patients in the carboplatin with vincristine arm in LGG cohort was continued for the prescribed number of cycles, as tolerated or until unacceptable toxicity, start of a new anti-neoplastic therapy, discontinuation at the discretion of the investigator or patient/legal guardian, lost to follow-up, death, study is terminated by the sponsor or until disease progression. Participants randomized to the carboplatin with vincristine treatment arm were allowed to cross over to receive dabrafenib in combination with trametinib after centrally confirmed RANO-defined disease progression. Crossover was allowed during the treatment period or the post-treatment period. After discontinuation of study treatment, all participants (LGG and HGG cohorts) were followed for safety for at least 30 days after the last dose of study treatment. All participants who discontinued study treatment for reasons other than disease progression, death, loss to follow up, or withdrawal of consent moved into the post-treatment efficacy follow-up phase. Finally, all participants were followed for survival once they discontinued study treatment for at least 2 years after the last patient first study treatment (except if consent was withdrawn, death, or the patient was lost to follow-up or discontinued study)
Source references
- references
- citation
- Gascon B, Gauvreau C, Yang A, Bennett J, Nobre L, Tabori U, Hawkins C, Tsang D, Pechlivanoglou P, Denburg A. Cost-Effectiveness of Dabrafenib Plus Trametinib Versus Standard Chemotherapy in BRAFV600E-Mutant Pediatric Low-Grade Glioma. JCO Oncol Pract. 2026 Feb 25:OP2501263. doi: 10.1200/OP-25-01263. Online ahead of print.
- pmid
- 41740060
- type
- DERIVED
- citation
- Bouffet E, Hansford JR, Garre ML, Hara J, Plant-Fox A, Aerts I, Locatelli F, van der Lugt J, Papusha L, Sahm F, Tabori U, Cohen KJ, Packer RJ, Witt O, Sandalic L, Bento Pereira da Silva A, Russo M, Hargrave DR. Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations. N Engl J Med. 2023 Sep 21;389(12):1108-1120. doi: 10.1056/NEJMoa2303815.
- pmid
- 37733309
- type
- DERIVED
- citation
- Hargrave DR, Terashima K, Hara J, Kordes UR, Upadhyaya SA, Sahm F, Bouffet E, Packer RJ, Witt O, Sandalic L, Kieloch A, Russo M, Cohen KJ; Investigators involved in the high-grade glioma cohort. Phase II Trial of Dabrafenib Plus Trametinib in Relapsed/Refractory BRAF V600-Mutant Pediatric High-Grade Glioma. J Clin Oncol. 2023 Nov 20;41(33):5174-5183. doi: 10.1200/JCO.23.00558. Epub 2023 Aug 29.
- pmid
- 37643378
- type
- DERIVED
- citation
- Barbato MI, Nashed J, Bradford D, Ren Y, Khasar S, Miller CP, Zolnik BS, Zhao H, Li Y, Bi Y, Shord SS, Amatya AK, Mishra-Kalyani PS, Scepura B, Al-Matari RA, Pazdur R, Kluetz PG, Donoghue M, Singh H, Drezner N. FDA Approval Summary: Dabrafenib in Combination with Trametinib for BRAFV600E Mutation-Positive Low-Grade Glioma. Clin Cancer Res. 2024 Jan 17;30(2):263-268. doi: 10.1158/1078-0432.CCR-23-1503.
- pmid
- 37610803
- type
- DERIVED
- citation
- Shahid S, Kushner BH, Modak S, Basu EM, Rubin EM, Gundem G, Papaemmanuil E, Roberts SS. Association of BRAF V600E mutations with vasoactive intestinal peptide syndrome in MYCN-amplified neuroblastoma. Pediatr Blood Cancer. 2021 Oct;68(10):e29265. doi: 10.1002/pbc.29265. Epub 2021 Jul 31.
- pmid
- 34331515
- type
- DERIVED
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-a67198831312df71a206
- requested nct id
- NCT02684058
- primary nct id
- NCT02684058
- source kind
- fda_spl_label
- source record id
- 235e3bc1-099b-4587-9d72-b02fcc3387d1
- source file sha256
- fc39a8c5cf96bf95ca20b85578140167b66b2741f7d9217f500d9ba0847ac058
- payload sha256
- 2b97039c25148e0c106a257cb62a81726e418742dcccdc8a0b055831102f432b
- payload
- application numbers
- NDA204114
- NDA217513
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-a67198831312df71a206
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT02684058
- occurrences
- context exact
- s who responded, DoR was ≥ 6 months for 78% of patients and ≥ 24 months for 44% of patients. CDRB436G2201 (G2201) Study – High-Grade Glioma Cohort Study G2201 (NCT02684058) was a multi-center, randomized, open-label, Phase II study of dabrafenib and trametinib in chemotherapy-naïve pediatric patients with BRAF V600E mutant low-gr
- end
- 22038
- exact text
- NCT02684058
- start
- 22027
- context exact
- ion-positive low-grade glioma (LGG) in pediatric patients aged 1 to < 18 years of age were evaluated in the multi-center, open-label trial (Study CDRB436G2201; NCT02684058). Patients with LGG (WHO grades 1 and 2) who required first systemic therapy were randomized in a 2:1 ratio to dabrafenib plus trametinib (D + T) or carboplati
- end
- 23539
- exact text
- NCT02684058
- start
- 23528
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00100.json
- source file sha256
- fc39a8c5cf96bf95ca20b85578140167b66b2741f7d9217f500d9ba0847ac058
- source json pointer
- /results/22/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 235e3bc1-099b-4587-9d72-b02fcc3387d1
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 0d4338caf57806a883c339d9753e714b1d79bae6603bf89c8b4a753601be41a2
- spl effective time
- 20260507
- spl set id
- 0002ad27-779d-42ab-83b5-bc65453412a1
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-db22a2084562688c6695
- requested nct id
- NCT02684058
- primary nct id
- NCT02684058
- source kind
- fda_spl_label
- source record id
- 6c546993-1f7f-409b-b108-60f22e9b948a
- source file sha256
- a4bef6778baed183e5bcf581938b0b23d3576dfd9eb6150f2904934a750c5fef
- payload sha256
- 3f31ace40410a0132e5ba700a61fab224c2576a1ba965aa4e99c402c0d4896d5
- payload
- application numbers
- NDA202806
- NDA217514
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-db22a2084562688c6695
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT02684058
- occurrences
- context exact
- s who responded, DoR was ≥ 6 months for 78% of patients and ≥ 24 months for 44% of patients. CDRB436G2201 (G2201) Study – High-Grade Glioma Cohort Study G2201 (NCT02684058) was a multi-center, randomized, open-label, Phase II study of dabrafenib and trametinib in chemotherapy-naïve pediatric patients with BRAF V600E mutant low-gr
- end
- 24795
- exact text
- NCT02684058
- start
- 24784
- context exact
- ion-positive low-grade glioma (LGG) in pediatric patients aged 1 to < 18 years of age were evaluated in the multi-center, open-label trial (Study CDRB436G2201; NCT02684058). Patients with LGG (WHO grades 1 and 2) who required first systemic therapy were randomized in a 2:1 ratio to dabrafenib plus trametinib (D + T) or carboplati
- end
- 26296
- exact text
- NCT02684058
- start
- 26285
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00400.json
- source file sha256
- a4bef6778baed183e5bcf581938b0b23d3576dfd9eb6150f2904934a750c5fef
- source json pointer
- /results/35/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 6c546993-1f7f-409b-b108-60f22e9b948a
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 529519a1bd82eb725efb50943c98c4faefad6f57654202e3d8518065ca819690
- spl effective time
- 20260520
- spl set id
- fee1e6b1-e1a5-4254-9f2e-a70e0f8dbdea
Preserved source evidence · Not medical advice