Feasibility of CSF and Plasma ctDNA in BRAF-altered Glioma During Treatment With Plixorafenib

Description

This clinical trial is designed as a pilot, signal-finding study to demonstrate the feasibility of detecting ctDNA at baseline and after 4 weeks of treatment (primary endpoint), as well as correlating with disease status as per radiographic response (RR; secondary endpoint). In addition, the investigators will generate preliminary data for activity of plixorafenib co-administered with cobicistat in this heavily-pretreated population. Patients with measurable (by Response Assessment in Neuro-Oncology (RANO 2.0)), recurrent BRAF-V600E mutant glioma will be screened and consented for the study prior to surgery. Patients will undergo pre-operative MRI and clinically-indicated resection or biopsy (specific approach as per treating neurosurgeon) for confirmation of progression and characterization of potential acquired resistance alterations. All patients will have a ventricular reservoir placed at time of surgery with CSF and plasma sampling. Patients will start the study drug (plixorafenib 900mg daily co-administered with cobicistat 150mg daily) 7-28 days post-operatively, when clinically stable. Patients will take the drug daily by mouth under fasting conditions continuously for 28-day cycles until progressive disease or up to 24 cycles. MRI will be performed post-operatively (between proof of delivery (POD#0) and start of study drug) for evaluation of measurable disease, after Cycle 1, then every 2 cycles. Blood and CSF samples will be obtained on day of surgery, at baseline, pre-C2, then with each MRI. A total of 12 evaluable patients will be enrolled. Patients who do not start drug will be replaced, up to a total of 15 patients.