CDRB436G2201, 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 relapsed or refractory High Grade Glioma (HGG)
Study ID: STU 032016-044
This is a multi-center, global, single arm, open-label, phase ii study evaluating the effect of dabrafenib in combination with trametinib in children and adolescent patients with BRaF V600 mutation positive relapsed, refractory, high grade gliomas (HGG). approximately 40 patients will be enrolled to receive oral dabrafenib twice daily and trametinib once daily based on weight, age and appropriate dose level. Patients may continue study treatment until disease progression or loss of clinical benefit as determined by the investigator, occurrence of unacceptable toxicity, withdrawal of consent or lost to follow-up, or sponsor termination of the study. all patients will be followed for survival for at least 2 years after the last study treatment (except if consent is withdrawn, patient death, lost to follow-up or study is discontinued). an interim analysis for futility will be implemented to allow possible termination of recruitment and the study in the event that there is insufficient efficacy.
1. Male or female between >= 6 and < 18 years of age at the time of signing the informed consent form. 2. Relapsed, progressed, or failed to respond to frontline therapy. Frontline therapy is presumed to be optimal surgical approach (biopsy or resection) with radiation and/or chemotherapy. 3. Histologically confirmed diagnosis of High Grade Glioma (HGG) (Grade III or IV glioma as defined by World Health Organization (WHO) histological classification system, revised 2016), including anaplastic pleomorphic xanthoastrocytoma (aPXA) and anaplastic gangliogliomas. 4. Locally determined and centrally confirmed measurable disease with minimal biperpendicular diameter that must be at least twice the imaging slice thickness to be used for efficacy assessments. (Both local and centrally confirmed results must show measurable disease to meet eligibility). 5. BRAF V600 mutation-positive tumor as locally determined using molecular methods in a Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory or equivalent, or at a Novartis designated central reference laboratory upon request. 6. Tumor tissue (newly obtained or archival paraffin blocks/slides) must be available and subsequently provided to Novartis for central confirmatory testing of HGG histopathology and BRAF mutational status. 7. Performance score of >= 50% according to the Karnofsky/Lansky performance status scale. 8. Females of child-bearing potential must be willing to practice acceptable methods of birth control. Additionally, females of childbearing potential must have a negative serum pregnancy test within 7 days prior to day 1. 9. Must have adequate bone marrow function in the absence of growth factor support and is defined as: - Absolute neutrophil count (ANC) >= 1000/[MICRO-SYMBOL]L; - Platelets >= 75,000/[MICRO-SYMBOL]L and transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to meeting this enrollment criteria - Hemoglobin >= 8.0 g/dL (may receive red blood cell transfusions) 10. Adequate renal function defined as: - Calculated Estimated Glomerular Filtration Rate (eGFR), or radioisotope GFR >= 90 mL/min/1.73 m2; or - A serum creatinine within the testing lab reference range (for age/gender, if available) 11. Adequate liver function defined as: - Bilirubin (sum of conjugated + unconjugated) <= 1.5 x upper limit of normal (ULN) for age - AST (aspartate aminotransferase) and ALT (alanine aminotransferase) <= 2.5 x ULN 12. Adequate cardiac function defined as: - Left ventricular ejection fraction (LVEF) greater than or equal to institutional lower limit of normal (LLN) by echocardiogram/ECHO (while not receiving medications for cardiac function) - Corrected QT (QTcF) interval <= 480 msecs. 13. Able to swallow capsules: - If less than 12 years old, must be >= 16 kg body weight - If >= 12 years old, must be >= 19 kg body weight 14. If receiving glucocorticoids, patient must be on a stable or weaning dose for at least 7 days prior to the first dose of study treatment. 15. Written informed consent/assent must be obtained prior to any protocol specific screening procedures being performed.
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- Theodore W Laetsch
NOVARTIS PHARMACEUTICALS CORPORATION
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