Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT03965494
Previous Study | Return to List | Next Study

AXL Inhibitor BGB324 in Treating Participants With Recurrent Glioblastoma Undergoing Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03965494
Recruitment Status : Recruiting
First Posted : May 29, 2019
Last Update Posted : July 2, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
BerGenBio ASA
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Drug: BGB 324 (before surgery) Drug: BGB 324 (after surgery) Early Phase 1

Detailed Description:

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Surgical PK Study of BGB324 in Recurrent Glioblastoma Patients
Actual Study Start Date : January 2, 2020
Estimated Primary Completion Date : December 1, 2022
Estimated Study Completion Date : December 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: AXL inhibitor BGB324 then surgery
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)
Given by mouth either BEFORE therapeutic conventional surgery
Other Names:
  • AXL Inhibitor BGB324
  • Bemcentinib

Experimental: Surgery then AXL inhibitor BGB324
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)
Given by mouth either AFTER therapeutic conventional surgery
Other Names:
  • AXL Inhibitor BGB324
  • Bemcentinib




Primary Outcome Measures :
  1. Proportion of patients who achieve a drug concentration at >= 1.0 uM level in contrast enhancing tumor tissue [ Time Frame: Up to 1 year ]
    Will be estimated using binomial distribution along with 90% confidence interval.


Secondary Outcome Measures :
  1. Change in AXL expression level [ Time Frame: Up to 1 year ]
    Change in AXL expression level (ng/mL) from baseline (before intervention) to post-intervention.

  2. Pharmacokinetics as measured by plasma maximum concentration (Cmax) (ug/mL) [ Time Frame: up to 30 days post-treatment ]
    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

  3. Pharmacokinetics as measured by plasma minimum concentration (Cmin) (ug/mL) [ Time Frame: up to 30 days post-treatment ]
    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

  4. Pharmacokinetics as measured by area under the curve (AUC) (ug/mL*hr) [ Time Frame: up to 30 days post-treatment ]
    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

  5. Toxicity as assessed by number of participants experiencing of adverse events [ Time Frame: Up to 1 year ]
    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)

  6. Overall survival [ Time Frame: up to 1 year ]
    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.

  7. Progression-free survival [ Time Frame: up to 1 year ]
    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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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:

    • 12 weeks from the completion of radiation
    • 6 weeks from a nitrosourea chemotherapy or mitomycin C
    • 3 weeks from a non-nitrosourea chemotherapy
    • 4 weeks from any investigational (not Food and Drug Administration [FDA]-approved) agents
    • 2 weeks from administration of a non-cytotoxic, FDA-approved agent, e.g., erlotinib, hydroxychloroquine, etc.)
    • 4 weeks from prior antiangiogenesis therapy (approved or investigational) (e.g., bevacizumab, aflibercept, ramucirumab, cediranib, cabozantinib, etc.)
    • 4 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)
  • Absolute neutrophil count >= 1,500/uL
  • Platelets >= 100,000/uL
  • Hemoglobin >= 9 g/dL
  • Total bilirubin < 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x institutional upper limit of normal
  • Creatinine =< institutional upper limit of normal OR creatinine clearance >= 60 ml/min/1.73m^2 for patients with creatinine levels above institutional normal
  • Activated partial thromboplastin time (APTT)/partial thromboplastin time (PTT) =< 1.5 x institutional upper limit of normal
  • Must have a 12-lead electrocardiogram with a measurable corrected QT using Fridericia's correction formula (QTcF) =< 450 msec
  • Must be able to provide written informed consent
  • Women of childbearing potential must have a negative serum pregnancy test prior to study entry. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and through 4 months after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of BGB324 administration
  • Must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder. Patients with prior malignancies must be disease-free for >= five years
  • Must be able to swallow whole capsules

Exclusion Criteria:

  • 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
  • Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible
  • Pregnant women are excluded from this study because the effects of BGB324 on a fetus are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BGB324, breastfeeding should be discontinued if the mother is treated with BGB324
  • Patients positive for human immunodeficiency virus (HIV) are NOT excluded from this study, but HIV-positive patients must have:

    • A stable regimen of highly active anti-retroviral therapy (HAART) not containing a strong inducer or inhibitor of CYP2C9
    • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
    • A CD4 count above 250 cells/uL and an undetectable HIV viral load on standard polymerase chain reaction (PCR)-based test

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03965494


Contacts
Layout table for location contacts
Contact: Serena Desideri, MD 4106144400 sdeside1@jhmi.edu
Contact: Joy Fisher, MA 4109553657 jfisher@jhmi.edu

Locations
Layout table for location information
United States, Alabama
Comprehensive Cancer Center at University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Clinical Trials Office - University of Alabama Comprehensive C    205-934-0309      
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231
Contact: Michaella Iacoboni, RN, BSN    410-955-8837    msheeh13@jhmi.edu   
Contact: Tamara Dobson-Brown       tdobson1@jhmi.edu   
Principal Investigator: Chetan Bettegowda, MD         
United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: Ken Winters       KWINTER1@hfhs.org   
Contact: Amanda Lewis       ALEWIS7@hfhs.org   
Principal Investigator: Tobias Walbert, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
National Cancer Institute (NCI)
BerGenBio ASA
Investigators
Layout table for investigator information
Study Chair: Ichiro Nakano, MD University of Alabama and Birmingham
Layout table for additonal information
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT03965494    
Other Study ID Numbers: ABTC-1701
IRB00184546 ( Other Identifier: JHM IRB )
UM1CA137443 ( U.S. NIH Grant/Contract )
First Posted: May 29, 2019    Key Record Dates
Last Update Posted: July 2, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
adult glioblastoma
Additional relevant MeSH terms:
Layout table for MeSH terms
Glioblastoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases