Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioblastoma

Central Nervous System Neoplasms

Nervous System Neoplasms

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Participants receive AXL inhibitor BGB324 PO 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.

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.

Given by mouth either BEFORE therapeutic conventional surgery

BGB 324 (before surgery)

Given by mouth either AFTER therapeutic conventional surgery

BGB 324 (after surgery)

Burt Nabors, MD

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.

AXL Inhibitor BGB324 in Treating Participants With Recurrent Glioblastoma Undergoing Surgery

Pilot Surgical PK Study of BGB324 in Recurrent Glioblastoma Patients

Will be estimated using binomial distribution along with 90% confidence interval.

Change in AXL expression level (ng/mL) from baseline (before intervention) to post-intervention.

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

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 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.

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

Spots Global Cancer Trial Database for bgb 324 (before surgery)