This phase I trial studies how well AXL inhibitor BGB324 works in treating participants with glioblastoma that has come back who are undergoing surgery. AXL inhibitor BGB324 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. Evaluate the penetration of AXL inhibitor BGB324 (BGB324) across the blood brain barrier measured by pharmacokinetics/drug concentration of 1.0 uM in tissue resected from a contrast enhancing region of the tumor in 60% of recurrent glioblastoma patients. SECONDARY OBJECTIVES: I. Determine AXL expression, phosphorylation state (AXL phosphospecific antibody if AXL is inhibited), and circulating soluble AXL levels. II. Determine the BGB324 concentration in tissue resected from a contrast non-enhancing region of the tumor. III. Characterize the steady state pharmacokinetics of BGB324 in patients with recurrent glioblastoma. IV. Estimate safety and tolerability of BGB324 for recurrent glioblastoma. V. Assess the progression-free and overall survival of patients with recurrent glioblastoma. OUTLINE: Participants are assigned to 1 of 2 groups. GROUP A: Participants receive AXL inhibitor BGB324 orally (PO) once daily (QD) on days 1-5, then undergo surgery 3-6 hours after last dose. Within 45 days, participants receive AXL inhibitor BGB324 PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. GROUP B: Participants undergo surgery, then within 45 days receive AXL inhibitor BGB324 PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up at 30 days.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Given by mouth either BEFORE therapeutic conventional surgery
Given by mouth either AFTER therapeutic conventional surgery
Comprehensive Cancer Center at University of Alabama at Birmingham
Birmingham, Alabama, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Henry Ford Hospital
Detroit, Michigan, United States
Memorial Sloan Kettering
New York, New York, United States
Proportion of patients who achieve a drug concentration at >= 1.0 uM level in contrast enhancing tumor tissue
Will be estimated using binomial distribution along with 90% confidence interval.
Time frame: Up to 1 year
Change in AXL expression level
Change in AXL expression level (ng/mL) from baseline (before intervention) to post-intervention.
Time frame: Up to 1 year
Pharmacokinetics as measured by plasma maximum concentration (Cmax) (ug/mL)
Samples for pharmacokinetic analysis will be collected at baseline, prior to dose on day of surgery, at 2, 4, 8, 12, 16, 20, and 24 hours after dosing; on course (C)1 day (D)1, at 2, 4, 6 and 24 hours on C1D15, C2D8, C2D15, prior to starting each course and 30 days post-treatment
Time frame: up to 30 days post-treatment
Pharmacokinetics as measured by plasma minimum concentration (Cmin) (ug/mL)
Samples for pharmacokinetic analysis will be collected at baseline, prior to dose on day of surgery, at 2, 4, 8, 12, 16, 20, and 24 hours after dosing; on course (C)1 day (D)1, at 2, 4, 6 and 24 hours on C1D15, C2D8, C2D15, prior to starting each course and 30 days post-treatment
Time frame: up to 30 days post-treatment
Pharmacokinetics as measured by area under the curve (AUC) (ug/mL*hr)
Samples for pharmacokinetic analysis will be collected at baseline, prior to dose on day of surgery, at 2, 4, 8, 12, 16, 20, and 24 hours after dosing; on course (C)1 day (D)1, at 2, 4, 6 and 24 hours on C1D15, C2D8, C2D15, prior to starting each course and 30 days post-treatment
Time frame: up to 30 days post-treatment
Toxicity as assessed by number of participants experiencing of adverse events
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Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Number of participants experiencing of adverse events grade 3 or higher as defined by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0)
Time frame: Up to 1 year
Overall survival
Time until death or the time of last known alive if lost to follow-up. Survival probability and a median time of survival will be estimated using Kaplan-Meier method along with 95% confidence interval.
Time frame: up to 1 year
Progression-free survival
Median time of progression-free survival will be estimated using Kaplan-Meier method along with 95% confidence interval. Tumor assessment will be conducted per Response Assessment in Neuro-Oncology (RANO): Complete Response (CR)= no change in size of T1-gadolinium-enhancing (T1-Gd+) disease, stable or reduced T2/FLAIR signal, no new lesion, no corticosteroid use, and stable or improved clinical status; Partial Response (PR)= ≥50% change in size of T1-Gd+ disease, stable or reduced T2/FLAIR signal, no new lesion, stable or reduced corticosteroid use, and stable or improved clinical status; Stable Disease (SD)= \<50% reduction to \<25% increase size of T1-Gd+ disease, stable or reduced T2/FLAIR signal, no new lesion, stable or reduced corticosteroid use, and stable or improved clinical status; Progressive Disease (PD)= ≥25% increase size of T1-Gd+ disease, or increased T2/FLAIR signal, or presence of new lesion, or worsening clinical status
Time frame: up to 1 year