AXL Inhibitor BGB324 in Treating Participants With Recurrent Glioblastoma Undergoing Surgery

NCT03965494 | Terminated Early Phase 1 DMC FDA Drug

• 3 other identifiers: ABTC-1701IRB00184546UM1CA137443
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult glioblastoma

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 1 year

Secondary Outcomes (7)

• Change in AXL expression level

  Up to 1 year

• Pharmacokinetics as measured by plasma maximum concentration (Cmax) (ug/mL)

  up to 30 days post-treatment

• Pharmacokinetics as measured by plasma minimum concentration (Cmin) (ug/mL)

  up to 30 days post-treatment

• Pharmacokinetics as measured by area under the curve (AUC) (ug/mL*hr)

  up to 30 days post-treatment

• Toxicity as assessed by number of participants experiencing of adverse events

  Up to 1 year

Study Arms (2)

AXL inhibitor BGB324 then surgery

EXPERIMENTAL

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.

Drug: BGB 324 (before surgery)

Surgery then AXL inhibitor BGB324

EXPERIMENTAL

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.

Drug: BGB 324 (after surgery)

Interventions

BGB 324 (before surgery) DRUG

Given by mouth either BEFORE therapeutic conventional surgery

Also known as: AXL Inhibitor BGB324, Bemcentinib

AXL inhibitor BGB324 then surgery

BGB 324 (after surgery) DRUG

Given by mouth either AFTER therapeutic conventional surgery

Also known as: AXL Inhibitor BGB324, Bemcentinib

Surgery then AXL inhibitor BGB324

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have histologically confirmed glioblastoma (GBM) that is progressive or recurrent following radiation therapy +/- chemotherapy. Patients with previous low-grade glioma who progressed after radiation therapy (RT)/chemotherapy and are biopsied and found to have GBM/gliosarcoma (GS) are eligible
• Patients must have measurable, supratentorial contrast-enhancing progressive or recurrent glioblastoma or gliosarcoma by magnetic resonance imaging (MRI) within 21 days of starting treatment. Patient must be able to tolerate MRIs
• May have had treatment for no more than 2 prior relapses
• Must have a tumor tissue form indicating availability of archived tissue from initial resection at diagnosis of GBM or GS, completed and signed by a pathologist. Sites must agree to provide this form within 14 days after treatment start. Availability of tissue is not a requirement for study participation
• The following intervals from previous treatments are required to be eligible:
• weeks from the completion of radiation
• weeks from a nitrosourea chemotherapy or mitomycin C
• weeks from a non-nitrosourea chemotherapy
• weeks from any investigational (not Food and Drug Administration \[FDA\]-approved) agents
• weeks from administration of a non-cytotoxic, FDA-approved agent, e.g., erlotinib, hydroxychloroquine, etc.)
• weeks from prior antiangiogenesis therapy (approved or investigational) (e.g., bevacizumab, aflibercept, ramucirumab, cediranib, cabozantinib, etc.)
• weeks from any immunotherapy intervention
• Patients must be undergoing surgery that is clinically indicated as determined by their care providers. Patients must be eligible for surgical resection according to the following criteria:
• \* Expectation that the surgeon is able to resect 0.05-0.10 cm\^3 (50-100 mg) of tumor from enhancing tumor and at least 0.05-0.10 cm\^3 (50-100 mg) from non-enhancing tumor with low risk of inducing neurological injury
• Must have a Karnofsky performance status \>= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)

You may not qualify if:

• Patients receiving any other investigational agents are ineligible
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to BGB324 are ineligible. The investigator brochure can be referenced for more information
• Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol. Patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs. Patients previously treated with an EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to treatment start
• Patients with a history of bleeding diathesis are ineligible
• Patients who have not recovered to \< Common Terminology Criteria for Adverse Events (CTCAE) grade 2 toxicities related to prior therapy are ineligible
• Patients considered at risk of QTc induced arrhythmias or uncontrolled or significant cardiovascular disease, including, but not limited to, any of the following are ineligible:
• Abnormal left ventricular ejection fraction on echocardiography (less than the lower limit of normal for a subject of that age at the treating institution or \< 45%)
• History of an ischemic cardiac event including myocardial infarction within 3 months of study entry
• Congestive cardiac failure of \> grade 2 severity according to the New York Heart Association as defined by symptomatic at less than ordinary levels of activity
• Unstable cardiac disease including unstable angina or hypertension as defined by the need for change in medication within the last 3 months
• History or presence of bradycardia (=\< 60 beats per minute \[bpm\]) or history of symptomatic bradycardia, left bundle branch block, cardiac pacemaker or significant atrial tachyarrhythmias as defined by the need for treatment
• Current treatment with any agent known to cause torsade de points which cannot be discontinued at least two weeks prior to treatment
• Known family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy
• Previous history of drug-induced QTc prolongation
• Screening 12-lead electrocardiogram (ECG) with a measurable QTcF \> 450 ms

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator
• BerGenBio ASA: collaborator

Study Sites (6)

Comprehensive Cancer Center at University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Memorial Sloan Kettering

New York, New York, 10065, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma

Interventions

bemcentinib; Postoperative Period

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Perioperative Period; Surgical Procedures, Operative; Patient Care; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Burt Nabors, MD

  University of Alabama and Birmingham

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2019
• First Posted: May 29, 2019
• Study Start: January 2, 2020
• Primary Completion: October 31, 2023
• Study Completion: October 31, 2023
• Last Updated: February 8, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)