Microtubule-Targeted Agent BAL101553 and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma

NCT03250299 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: ABTC 1601CDI-CS-004IRB00131687
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 8

Brief Summary

This Phase I study investigated the side-effects and best dose of microtubule-targeted agent BAL101553 when given together with radiation therapy in treating patients with newly-diagnosed O6-methylguanine-DNA methyltransferase (MGMT) promoter unmethylated glioblastoma (GBM). Drugs used in chemotherapy, such as microtubule-targeted agent BAL101553, work in different ways to stop the growth of tumor cells, either by killing the cells, stopping them from dividing, or stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving microtubule-targeted agent BAL101553 and radiation therapy may work better in treating patients with GBM.

Conditions

Glioblastoma; MGMT-Unmethylated Glioblastoma

Keywords

Glioblastoma; Brain tumor; Lisavanbulin; BAL101553

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Dose-Limiting Toxicities (DLTs) for Each Maximal Tolerated Dose (MTD)-Determining Dose Cohort

  A DLT was defined as a clinically-significant adverse event (AE) or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications. Any DLT had to be a toxicity considered at least possibly related to BAL101553 or the combination of BAL101553 and radiation.

  Up to 10 weeks

Secondary Outcomes (3)

• Number of Patients With Grade 3 to Grade 5 Adverse Events (AEs)

  up to 10 weeks

• Overall Survival (OS) Time

  Day 1 to date of death - up to 1679 days (4.6 years)

• Progression Free Survival (PFS) Time

  Day 1 to date of disease progression - 1092 days (3.0 years)

Study Arms (1)

Dose Finding

EXPERIMENTAL

Fixed 3+3 dose escalation of BAL101553 (7 days per week), combined with RT days 1-5 for 6 weeks followed by 4 week rest.

Drug: Microtubule-Targeted Agent BAL101553; Radiation: Radiation Therapy

Interventions

Microtubule-Targeted Agent BAL101553 DRUG

Given PO

Also known as: BAL101553, Microtubule-targeted Agent BAL101553

Dose Finding

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Irradiate, irradiated, irradiation, RADIATION, Radiation, radiation therapy, Radiation Therapy, Radiotherapeutics, radiotherapy, Radiotherapy, RT, Therapy, Radiation

Dose Finding

Eligibility Criteria

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

You may qualify if:

• Patients must have had histologically-proven GBM
• Patients must have recovered from the immediate post-operative period
• Patients must have had tumor MGMT methylation status of unmethylated as determined by local pathologist using a Clinical Laboratory Improvement Act (CLIA)-approved diagnostic test; results of routinely-used methods for MGMT methylation testing (e.g. methylation-specific \[MS\]- polymerase chain reaction \[PCR\] or quantitative PCR) were acceptable
• Patients must have been be able to undergo magnetic resonance imaging (MRI) of the brain with gadolinium
• Patients must not have received prior radiation therapy (RT), chemotherapy, immunotherapy or therapy with a biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocytes, lymphokine-activated killer cells, or gene therapy), or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed
• Patients must have had a tumor tissue form indicating availability of archived tissue from initial resection at diagnosis of GBM, completed and signed by a pathologist
• Patients must have had 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/micro liter (mcL)
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9 g/dL
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN), unless the patient has known Gilbert's syndrome
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN
• Creatinine =\< 1.5 x ULN
• Creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels \> ULN
• Activated partial thromboplastin time (APTT)/partial thromboplastin time (PTT) =\< 1.5 x ULN

You may not qualify if:

• Patients receiving any other investigational agent
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to BAL101553
• Patients on drugs that are strong inhibitors and/or inducers of CYP2C9, CYP2C19 or CYP3A4 (including enzyme-inducing anti-epileptic drugs EIAEDs\]), were not eligible for the study; patients taking non-EIAEDs were permitted to take part in the study; patients previously treated with any of the prohibited concomitant medications listed above may have been enrolled if they had been off the medication for \>= 10 days prior to the first dose of BAL101553
• Patients may not have been on coumarin anti-coagulants (warfarin, etc.); heparin, low-molecular weight heparin (LMWH), or other antithrombotic medications were permitted
• Patients with gastrointestinal disease, or those who had a procedure that was expected to interfere with the oral absorption or tolerance of BAL101553 (e.g., functionally-relevant gastrointestinal obstruction, or frequent vomiting unresolved upon anti-emetic supportive care)
• Patients with peripheral neuropathy \>= Common Terminology Criteria for Adverse Events (CTCAE) grade 2
• Patients with ataxia \>= CTCAE grade 2
• Patients with known acute or chronic hepatitis B or hepatitis C infection
• Patients with systolic blood pressure (SBP) \>= 140 mmHg or diastolic blood pressure (DBP) \>= 90 mmHg at the screening visit were ineligible; patients with an initial clinic blood pressure (BP) \>= 140/90 mmHg may be included if SBP \< 140 mmHg and DBP \< 90 mmHg is confirmed in two subsequent BP measurements on the same day
• Patients with BP combination treatment with more than two antihypertensive medications were ineligible
• Significant cardiac disease or abnormality, including any of the following:
• Left ventricular ejection fraction \< 50% at screening (assessed by echocardiography, cardiac MRI or multigated acquisition \[MUGA\])
• Corrected QT Fridericia's correction formula (QTcF) \> 470 ms on screening electrocardiogram (ECG), or a clinically-relevant ECG abnormality
• Congenital long QT syndrome
• History of sustained ventricular tachycardia, ventricular fibrillation, or torsades de pointes

Sponsors & Collaborators

• Basilea Pharmaceutica: lead
• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: collaborator

Study Sites (8)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35294-3410, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Abrams Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Hillman Cancer Center at University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

lisavanbulin; Radiotherapy; Radiation; Therapeutics

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Physical Phenomena

Results Point of Contact

• Title: Thomas Kaindl, MD, Global Medical Director
• Organization: Basilea Pharmaceutica International Ltd (Basilea)

thomas.kaindl@basilea.com

+41615671505

Study Officials

• Matthias Holdhoff, MD

  National Cancer Institute (NCI)

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2017
• First Posted: August 15, 2017
• Study Start: December 15, 2017
• Primary Completion: June 3, 2022
• Study Completion: August 24, 2022
• Last Updated: June 24, 2024
• Results First Posted: June 24, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)