A Trial to Evaluate Deoxyribonucleic) in BRAF (V-raf Murine Sarcoma Viral Oncogene Homolog B1)-Altered Glioma During Treatment With Plixorafenib Alone or With Retifanlimab
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Summary
The investigators will evaluate the sensitivity of ctDNA from plasma and CSF at baseline (defined as C1D1) and over time in response to treatment with plixorafenib alone or in combination with retifanlimab in patients with BRAF-V600E mutant glioma refractory to prior therapies.
Description
This clinical trial is designed as a pilot, signal-finding study to demonstrate the feasibility of detecting ctDNA at C1D1 (baseline) and pre-C2 (week 4) (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 the activity of plixorafenib co-administered with retifanlimab in this heavily-pretreated population. Patients with measurable (by RANO 2.0), recurrent BRAF-V600E mutant glioma will be screened and consented for the study prior to surgery. Patients will undergo…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Arm A Only: * Patient must have received prior BRAF and/or MEK inhibitor therapy. 1. Prior RAF dimer disruptor or pan-RAF inhibitor not allowed 2. Prior immunotherapy allowed * The following intervals from previous treatments should have elapsed prior to enrollment: a. BRAFi/MEKi should be stopped 2 weeks prior to surgery * Patients must be maintained on a stable or decreasing dose of systemic corticosteroid regimen (no increase for 5 days) prior to screening MRI. No maximum dose. Topical and inhaled steroid treatment is allowed. Inclusion Arm B Only: * Patient must have r…
Interventions
- DrugPlixorafenib
Patients will start the study drug (plixorafenib 900mg daily 30 minutes after a full meal or meal supplement) 7-28 days post-operatively, when clinically stable. Patients will take the drug daily by mouth continuously for 28-day cycles until progressive disease or up to 24 cycles. MRI will be performed post-operatively (between surgery and start of study drug) for evaluation of measurable disease, at the beginning of Cycle 2, then at the beginning of every odd cycle. Blood and CSF samples will be obtained on day of surgery, C1D1 (baseline), pre-C2 (week 4) and with every odd cycle up to and including C7 and EOT.
- DrugRetifanlimab
Investigators will evaluate the sensitivity of ctDNA from plasma and CSF at baseline and over time in response to treatment with plixorafenib alone or in combination with retifanlimab in patients with BRAF-V600E mutant glioma refractory to prior therapies.
Location
- Johns HopkinsBaltimore, Maryland