Sample size calculation
midline glioma, bleeding, neurologic adverse, high-grade glioma, infection, PD
INFECTION, BLEEDING, PATHOLOGY, COMPLICATIONS
The primary aim of this study is to assess the safety and feasibility of dialysis catheter placement and use. This is intended to be a preliminary trial to investigate safety and feasibility. As such, this trial will initially be limited to 5 evaluable participants, with possible expansion by a later amendment. Initially 2 participants with recurrent cortical high-grade glioma will be enrolled on study to assess safety and feasibility of microdialysis placement and evaluation with real-time pharmacokinetic measurements conducted. Then 3 participants with recurrent diffuse midline glioma will be enrolled on study.For purposes of this preliminary evaluation, the intra-tumoral microdialysis placement will be considered feasible for a given participant if we are able to place the catheter and obtain analyzable dialysate samples in at least 7 but preferably 10 (80%) or more of the 13 intended time points to evaluate the concentration of agents (participants who are not evaluable by having only 6 or fewer analyzable samples, or for other reasons, will be replaced) with no participants experiencing serious complications with microdialysis insertion/maintenance (no Grade 3 or higher bleeding, infection or neurologic adverse events in any participant). The timing of the usable dialysate samples will also determine if the results are adequately spread out over the intended time interval to demonstrate a feasible outcome for that participant. If so, this will be considered sufficient for purposes of this preliminary, exploratory study. If the placement was done with no serious complications in any participant, and if adequate, usable samples are able to be obtained from the microdialysis catheter in at least 4 of the 5 participants, then further use of this device may be considered in this trial by an amendment, or in a subsequent study, either of which would include a formal power analysis to justify the number of participants to enroll on the basis of a defined primary endpoint.Exploratory aims of the study are to conduct genomic analysis from tissue and pharmacokinetic studies during maintenance therapy. Descriptive statistics will be obtained (no interventions yielding comparison of participant groups). As such, no formal power analysis will be performed related to the exploratory endpoints. Priority for tissue studies 1) pathology, 2) molecular profiling, 3) pharmacology, 4) PDX modeling. Given the small study population, clinical data will be presented as median with range and categorical variables presented as proportions (%). All PK and PD samples will be batched until further analysis. It is expected that up to 1 year may be required to enroll up to 5 evaluable participants. To allow for a small number of inevaluable participants to be replaced, the accrual ceiling will be set at 7 participants.