BPM31510 in Treating Patients With Recurrent High-Grade Glioma Previously Treated With Bevacizumab

Sponsor

Seema Nagpal (Other)

Overall Status

Completed

CT.gov ID

NCT03020602

Collaborator

(none)

Enrollment

Location

Arm

53.7

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase I trial studies the side effects and best dose of ubidecarenone injectable nanosuspension (BPM31510) in treating patients with high-grade glioma (anaplastic astrocytoma or glioblastoma) that has come back and have been previously treated with bevacizumab. BPM31510 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition or Disease	Intervention/Treatment	Phase
Gliosarcoma Recurrent Glioblastoma Astrocytoma of Brain Glioblastoma	Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Ubidecarenone Injectable Nanosuspension	Phase 1

Detailed Description

Primary Objective:

Assess the safety and tolerability of BPM31510 plus vitamin K in subjects with high-grade glioma(HGG), defined as anaplastic astrocytoma (AA) or glioblastoma (GB) that has recurred on a BEV containing regimen.

Secondary Objectives:

To evaluate plasma pharmacokinetics (PK) when BPM31510 plus vitamin K is given to subjects with HGG recurrent on a BEV containing regimen.

Exploratory Objectives:

Estimate the overall survival in subjects with HGG recurrent on a BEV containing regimen from the 1st day of infusion of BPM31510 plus vitamin K to death.
To evaluate the effects of BPM31510 plus vitamin K on shifting HGG metabolism to aerobic respiration by PET imaging.
To evaluate the effects of BPM1510 plus vitamin K on MRI imaging by Response Assessment in Neuro Oncology (RANO) criteria [specifically progression free survival (PFS) and response rate (RR)].
To evaluate plasma pharmacodynamics (PD) when BPM31510 plus vitamin K is given to subjects with HGG recurrent on a BEV containing regimen.

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of BPM31510 Plus Vitamin K in Subjects With High-Grade Glioma That Has Recurred on a Bevacizumab Containing Regimen

Actual Study Start Date :

Jan 4, 2017

Actual Primary Completion Date :

Apr 4, 2019

Actual Study Completion Date :

Jun 26, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (BPM31510) Patients receive ubidecarenone injectable nanosuspension IV over 72 hours twice weekly. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis Correlative studies Other: Pharmacological Study Correlative studies Drug: Ubidecarenone Injectable Nanosuspension Given IV Other Names: BP31510 Coenzyme Q10 Injectable Nanosuspension Ubiquinone Injectable Nanosuspension

Arm

Intervention/Treatment

Experimental: Treatment (BPM31510)

Patients receive ubidecarenone injectable nanosuspension IV over 72 hours twice weekly. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis

Correlative studies

Other: Pharmacological Study

Correlative studies

Drug: Ubidecarenone Injectable Nanosuspension

Given IV

Other Names:

BP31510

Coenzyme Q10 Injectable Nanosuspension

Ubiquinone Injectable Nanosuspension

Outcome Measures

Primary Outcome Measures

Percentage of patients with dose-limiting toxicities defined as thrombocytopenia >= grade 3, hemorrhage >= grade 3, and INR elevation >= grade 2 assessed by CTCAE v4.03 [Up to 28 days]
Will be tabulated at each dose, along with the result of the pooled adjacent violators algorithm as implemented in the Modified Toxicity Probability Interval (equal weights, and the weighted mean solver).

Secondary Outcome Measures

Incidence of adverse events graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) version (v)4.03 [Up to 30 days after last dose of BPM3150]
Will be tabulated separately for each dose cohort, by Medical Dictionary for Regulatory Activities (MedDRA) major organ system and severity.

Other Outcome Measures

Brain tumor metabolism as measured by PET [Up to 8 weeks]
Standardized uptake value (SUV) of the HGG will be measured. SUV is the standard PET measure.
Overall survival (OS) [From the date of BPM31510 initiation to death, assessed for up to 3 years]
Kaplan-Meier survival estimates for OS will be presented for data at the maximum tolerated dose, with a 95% confidence interval using Greenwood's formula at 3.5 months and 7 months.
PFS assessed by RANO criteria [Up to 3 years]
Response rate assessed by RANO criteria [Up to 3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Be ≥ 18 years of age
Have a life expectancy ≥ 6 weeks
Have a Karnofsky Performance Score (KPS) ≥ 60
Have pathologically proven GB, gliosarcoma (WHO IV), or anaplastic astrocytoma (WHO

in recurrence after treatment with bevacizumab

Be at least 14 days from the last administration of bevacizumab
Be at least 28 days from last administration of cytotoxic chemotherapy or other investigational agent
Have received radiation therapy with concurrent temozolomide. Total radiation dosage can range from 5400 to 6000 cGy administered in daily fractions of 150 to 200 cGy over 6 weeks, or the equivalent in a hypofractionated protocol (for example, 4000cGy in 15 fractions or 2500cGy in 5 fractions). Patients who are MGMT negative do not need to have received temozolomide.
Have adequate organ and marrow function as follows (all required):
ANC ≥ 1500 mm3
Platelets ≥ 100,000/mm3
Hemoglobin ≥ 9 g/dL
Serum creatinine ≤ 1.8 mg/dL or creatinine clearance > 50 mL/min Bilirubin ≤ 1.5 mg/dL
Alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
Aspartate transaminase (AST) ≤ 2.5 x ULN
Prothrombin time (PT) ≤ 1.5 x ULN
International Normalized Ratio (INR) ≤ 1.5 x ULN
Partial thromboplastin time (PTT) ≤ 1.5 x ULN
Subjects of childbearing potential must agree to use hormonal or barrier birth control with spermicidal gel to avoid pregnancy during the study
Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

Has a history of spontaneous or tumor related cerebral hemorrhage; or has cerebral hemorrhage as determined by the screening FDG PET CT and MRI. This does not include stable post operative blood products seen on a gradient echo MRI sequence.
Has the any of the following cardiac history:
Active heart disease including myocardial infarction within previous 3 months
Symptomatic coronary artery disease
Arrhythmias not controlled by medication
Unstable angina pectoris
Uncontrolled or symptomatic congestive heart failure (NYHA class III and IV) 3.2.3 Uncontrolled or severe coagulopathies or a history of clinically significant bleeding within the past 6 months, including any of the following, but not limited to:
Epistaxis
Hemoptysis
Hematochezia
Hematuria
Gastrointestinal bleeding
Spontaneous or tumor related intracranial hemorrhage
Known predisposition for bleeding such as von Willebrand's disease or other such condition(s)
Uncontrolled concurrent illness that would limit compliance with study requirements, including any of the following, but limited to:
Uncontrolled infection.
Psychiatric illness/social situations
Prior malignancy except for non melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 3 years prior to 1st dose of investigational drug
Receiving any of the following medications:
Therapeutic doses of any anticoagulant, including low molecular weight heparin (LMWH). Concomitant use of warfarin, even at prophylactic doses, is prohibited
Digoxin, digitoxin, lanatoside C, or any type of digitalis alkaloids.
Colony stimulating factors (CSFs) that cannot be held during the monitoring period for dose limiting toxicities (DLT)
Has significant toxicities from prior treatment that have not resolved or stabilized
Known allergy to Coenzyme Q10
Known allergy or adverse reaction to oral, subcutaneous, or intravenous vitamin K
Is pregnant or lactating
Known to be positive for the human immunodeficiency virus (HIV). Note: HIV testing is not required for eligibility, but if performed previously and was positive, the subject is ineligible.