Dabrafenib Combined With Trametinib After Radiation Therapy in Treating Patients With Newly-Diagnosed High-Grade Glioma
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|ClinicalTrials.gov Identifier: NCT03919071|
Recruitment Status : Recruiting
First Posted : April 18, 2019
Last Update Posted : November 13, 2020
|Condition or disease||Intervention/treatment||Phase|
|Anaplastic Astrocytoma Anaplastic Ganglioglioma Anaplastic Pleomorphic Xanthoastrocytoma Glioblastoma Malignant Glioma WHO Grade III Glioma||Drug: Dabrafenib Mesylate Radiation: Radiation Therapy Drug: Trametinib Dimethyl Sulfoxide||Phase 2|
I. To estimate the event-free survival (EFS) distribution for newly-diagnosed patients with BRAFV600-mutant high-grade glioma (HGG) without H3 K27M mutations excluding anaplastic pleomorphic xanthoastrocytoma (aPXA) and anaplastic ganglioglioma (aGG) treated with radiation therapy followed by a maintenance combination of dabrafenib mesylate (dabrafenib) and trametinib dimethyl sulfoxide (trametinib) and to compare this EFS to contemporary historical controls.
I. To describe the overall survival (OS) distribution for newly-diagnosed patients with BRAFV600-mutant HGG without H3 K27M mutations excluding aPXA and aGG treated with radiation therapy followed by a maintenance combination of dabrafenib and trametinib.
II. To describe the EFS and overall survival (OS) distribution for newly-diagnosed patients with BRAFV600E-mutant aPXA and aGG without H3 K27M mutations treated with radiation therapy followed by a maintenance combination of dabrafenib and trametinib.
III. To define and evaluate the toxicities of combination therapy with dabrafenib and trametinib after radiation therapy in newly-diagnosed patients with HGG.
I. To bank tumor specimens and body fluids (blood, urine and cerebrospinal fluid) for future studies.
Patients undergo standardized local radiation therapy (RT) 5 days a week (Monday-Friday) for 6-7 weeks. Four weeks after completion of RT, patients receive dabrafenib mesylate orally (PO) twice daily (BID) and trametinib dimethyl sulfoxide PO once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at disease relapse, every 3 months for year 1, every 4 months for year 2, every 6 months for year 3, then annually for years 4-5.
|Study Type :||Interventional|
|Estimated Enrollment :||58 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of Dabrafenib (NSC# 763760) With Trametinib (NSC# 763093) After Local Irradiation in Newly-Diagnosed BRAF V600-Mutant High-Grade Glioma (HGG)|
|Actual Study Start Date :||October 2, 2019|
|Estimated Primary Completion Date :||June 1, 2022|
|Estimated Study Completion Date :||June 1, 2022|
Experimental: Treatment (radiation therapy, dabrafenib, trametinib)
Patients undergo standardized local RT 5 days a week (Monday-Friday) for 6-7 weeks. Four weeks after completion of RT, patients receive dabrafenib mesylate PO BID and trametinib dimethyl sulfoxide PO QD on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
Drug: Dabrafenib Mesylate
Radiation: Radiation Therapy
Drug: Trametinib Dimethyl Sulfoxide
- Event-free survival (EFS) for stratum 1 [ Time Frame: From the date of diagnosis until disease progression date, secondary malignant neoplasm occurrence date, death date of any cause, or last follow-up, assessed up to 5 years ]The EFS curve for the new treatment cohort (Stratum 1) will be estimated by Kaplan Meier estimates. A 2-sample, 1 sided log-rank test will be used to test whether the EFS distribution is better in new treatment compared with historical control. Calculation of the EFS will be based on the site determination as central review will be performed retrospectively.
- Overall survival (OS) for stratum 1 and stratum 2 [ Time Frame: From the date of diagnosis until death date of any cause or last follow up date, assessed up to 5 years ]The OS curve for the new treatment cohort (Stratum 1) will be estimated by Kaplan Meier estimates. A 2-sample, 1 sided log-rank test will be used to test whether the OS distribution is better in new treatment compared with historical control. For Stratum 2, Kaplan Meier estimates will be provided for OS distribution.
- Event-free survival (EFS) for stratum 2 [ Time Frame: Follow up date, assessed up to 5 years ]For Stratum 2, Kaplan Meier estimates will be provided for EFS distribution .
- Incidence of adverse events [ Time Frame: Up to 5 years ]Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Grade 3 and higher toxicities observed by cycle will be listed for each stratum separately. The grade 3 and higher toxicities observed by cycle and by system organ class for the eligible patients will also be listed for each stratum separately. Toxicity data will be reported separately for the radiation therapy phase versus the maintenance therapy phase for clarity of attribution. Toxicity monitoring will include toxicities such as grade 2 or higher pyrexia, uveitis, retinal vein occlusion, retinal pigment epithelial detachment, and decreased left ventricular ejection fraction.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03919071
|Principal Investigator:||Rishi R Lulla||Children's Oncology Group|