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Trial record 1 of 1 for:    CDRB436G2201
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Phase II Pediatric Study With Dabrafenib in Combination With Trametinib in Patients With HGG and LGG

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ClinicalTrials.gov Identifier: NCT02684058
Recruitment Status : Recruiting
First Posted : February 17, 2016
Last Update Posted : January 31, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE February 4, 2016
First Posted Date  ICMJE February 17, 2016
Last Update Posted Date January 31, 2020
Actual Study Start Date  ICMJE December 28, 2017
Estimated Primary Completion Date November 11, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 13, 2018)
  • HGG cohort: Overall response rate (ORR) [ Time Frame: Within the first 32 weeks of treatment ]
    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.
  • LGG cohort: Overall response rate (ORR) [ Time Frame: Within the first 32 weeks of treatment ]
    LGG cohort: ORR as determined by blinded central independent assessment based on MRI or CT scans using RANO criteria.
Original Primary Outcome Measures  ICMJE
 (submitted: February 11, 2016)
Overall response rate (ORR) [ Time Frame: Within the first 4 months of treatment ]
ORR as determined by local assessment based on Magnetic resonance imaging MRI) or CT (CAT) scans using Response Assessment in Neuro-Oncology Criteria (RANO) criteria.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 13, 2018)
  • HGG cohort: Overall response rate (ORR) [ Time Frame: Within the first 32 weeks of treatment ]
    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)
  • HGG and LGG cohorts: Duration of response (DOR) [ Time Frame: Within the first year of treatment ]
    HGG and LGG cohorts: DOR as assessed separately by investigator and central review based on MRI or CT scans using RANO criteria
  • HGG and LGG cohorts: Time to response (TTR) [ Time Frame: Within the first year of treatment ]
    HGG and LGG cohorts: TTR as assessed separately by investigator and central review based on MRI or CT scans using RANO criteria
  • HGG and LGG cohorts: Overall survival (OS) [ Time Frame: 2 years from last patient dosed ]
    HGG and LGG cohorts: OS as defined as the time from first dose to death due to any cause
  • HGG and LGG cohorts: Progression free survival (PFS) [ Time Frame: Within 4 months of treatment ]
    HGG and LGG cohorts: PFS as assessed separately by investigator and central review based on MRI or CT scans using RANO criteria
  • Patients on DRB+TMT: Area under the curve (AUClast) [ Time Frame: Within the first month of treatment ]
    Patients on DRB+TMT: Assessed from time zero to the last measurable sampling time
  • Patients on DRB+TMT: Area under the curve (AUCtau) [ Time Frame: Within the first month of treatment ]
    Patients on DRB+TMT: Calculated to the end of a dosing interval at steady state (12 hours)
  • Patients on DRB+TMT: Maximum Plasma Concentration (Cmax) [ Time Frame: Within the first month of treatment ]
    Patients on DRB+TMT: The maximum (peak) observed plasma drug concentration after a single dose
  • Patients on DRB+TMT: Time to reach maximum concentration (Tmax) [ Time Frame: Within the first month of treatment ]
    Patients on DRB+TMT: The time to reach maximum (peak) concentration of study drug after a single dose
  • Patients on DRB+TMT: Elimination half-life (T1/2) [ Time Frame: Within the first month of treatment ]
    Patients on DRB+TMT: The elimination half-life associated with the terminal slope of a semi-log concentration-time curve
  • Patients on DRB+TMT: Predose plasma concentration (Ctrough) [ Time Frame: Within the first month of treatment ]
    Patients on DRB+TMT: Measured concentration at the end of a dosing interval at steady state, taken directly before next study drug administration).
  • HGG and LGG cohorts: Adverse events [ Time Frame: From first dose to end of treatment (EOT) ]
    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
  • HGG and LGG cohorts: Vital signs [ Time Frame: First dose to end of treatment ]
    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.
  • HGG and LGG cohorts: Abnormal lab values [ Time Frame: First dose to end of treatment ]
    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
  • HGG and LGG cohorts: Changes in Electrocardiogram (ECG) [ Time Frame: First dose to end of treatment ]
    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
  • HGG and LGG cohorts: ECHO [ Time Frame: First dose to end of treatment ]
    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.
  • LGG cohort: Overall response rate (ORR) [ Time Frame: Within the first 32 weeks of treatment ]
    LGG cohort: ORR as determined by investigator assessment based on MRI or CT scans using RANO criteria
  • HGG and LGG cohort: Palatability of pediatric formulations [ Time Frame: Within the first 5 weeks of treatment ]
    HGG and LGG cohort: Palatability questionnaire data for DRB suspension and TMT solution
  • LGG cohort: PROMIS Parent Proxy scale [ Time Frame: Within the first 32 weeks of treatment ]
    LGG cohort only: PROMIS parent proxy scale to estimate differences between treatment groups
  • HGG and LGG Cohorts: Clinical benefit rate (CBR) [ Time Frame: Within the first 24 weeks of treatment ]
    HGG and LGG cohorts: CBR as assessed separately by investigator and central review of MRI and CT scans per RANO criteria
  • LGG cohort: 2 year Overall survival (OS) [ Time Frame: 2 years from first dose ]
    LGG cohort: OS as defined as the time from the first dose to death due to any cause
Original Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2016)
  • Overall response rate (ORR) [ Time Frame: Within the first 4 months of treatment ]
    ORR as determined by central assessment based on Magnetic resonance imaging (MRI) or CT (CAT)scans using Response Assessment in Neuro-Oncology (RANO criteria)
  • Duration of response (DOR) [ Time Frame: Within the first year of treatment ]
    DOR as determined by local and central assessment based on MRI or CT scans using RANO criteria
  • Progression free survival (PFS) [ Time Frame: Within the first year of treatment ]
    PFS as determined by local and central assessment based on MRI or CT scans using RANO criteria
  • Overall survival (OS) [ Time Frame: 2 years from last patient dosed ]
    OS as defined as the time from first dose to death due to any cause
  • Overall response (OR) [ Time Frame: Within 4 months of treatment ]
    OR as determined by central assessment based on MRI or CT scans using RANO criteria in patients with centrally confirmed HGG, BRAF V600 mutation and measurable disease
  • Duration of response (DOR) [ Time Frame: Within 4 months of treatment ]
    DOR as determined by central assessment based on MRI or CT scans using RANO criteria in patients with centrally confirmed HGG, BRAF V600 mutation and measurable disease
  • Progression-free survival (PFS) [ Time Frame: Within 4 months of treatment ]
    PFS as determined by central assessment based on MRI or CT scans using RANO criteria in patients with centrally confirmed HGG, BRAF V600 mutation and measurable disease
  • Overall survival (OS) [ Time Frame: Within 4 months of treatment ]
    OS as determined by central assessment based on MRI or CT scans using RANO criteria in patients with centrally confirmed HGG, BRAF V600 mutation
  • Area under the curve (AUClast) [ Time Frame: Within the first month of treatment ]
    Assessed from time zero to the last measurable sampling time
  • Area under the curve (AUCtau) [ Time Frame: Within the first month of treatment ]
    Calculated to the end of a dosing interval at steady state (12 hours)
  • Maximum Plasma Concentration (Cmax) [ Time Frame: Within the first month of treatment ]
    The maximum (peak) observed plasma drug concentration after a single dose
  • Time to reach maximum concentration (Tmax) [ Time Frame: Within the first month of treatment ]
    The time to reach maximum (peak) concentration of study drug after a single dose
  • Elimination half-life (T1/2) [ Time Frame: Within the first month of treatment ]
    The elimination half-life associated with the terminal slope of a semi-log concentration-time curve
  • Predose plasma concentration (Ctrough) [ Time Frame: Within the first month of treatment ]
    Measured concentration at the end of a dosing interval at steady state, taken directly before next study drug administration).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Pediatric Study With Dabrafenib in Combination With Trametinib in Patients With HGG and LGG
Official Title  ICMJE 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)
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: dabrafenib
    dabrafenib oral, twice daily.
    Other Name: DRB436
  • Drug: trametinib
    trametinib oral, once daily.
    Other Name: TMT212
  • Drug: Carboplatin with vincristine
    Chemotherapy of carboplatin with vincristine - LGG only
Study Arms  ICMJE
  • Experimental: HGG cohort: Dabrafenib and trametinib
    HGG cohort: All patients in the HGG cohort will receive DRB+TMT
    Interventions:
    • Drug: dabrafenib
    • Drug: trametinib
  • Active Comparator: LGG cohort: Carboplatin with vincristine
    LGG cohort: Patients randomized 2:1 to either DRB+TMT or active comparator chemotherapy.
    Intervention: Drug: Carboplatin with vincristine
  • Experimental: LGG cohort: Dabrafenib and trametinib
    LGG cohort: Patients randomized 2:1 to either DRB+TMT or active comparator chemotherapy.
    Interventions:
    • Drug: dabrafenib
    • Drug: trametinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 8, 2018)
142
Original Estimated Enrollment  ICMJE
 (submitted: February 11, 2016)
30
Estimated Study Completion Date  ICMJE January 6, 2025
Estimated Primary Completion Date November 11, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Months to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Canada,   Czechia,   Denmark,   Finland,   France,   Germany,   Italy,   Japan,   Netherlands,   Russian Federation,   Spain,   Sweden,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02684058
Other Study ID Numbers  ICMJE CDRB436G2201
2015-004015-20 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP