Phase I Pilot Study to Evaluate the Anti-glioblastoma Effect of S-Gboxin in Standard Treatment of Glioblastoma/Diffuse Midline Glioma and Response to Treatment (Regardless of Mutation Status)

Petrov, Andrey10 enrolled

Overview

The objective of this pilot study is to evaluate the efficacy of adding S-Gboxin to standard RT/TMZ treatment protocols in patients with glioblastoma multiforme (GBM) or midline glioma (DMG), regardless of their mutation status

This is a pilot study to evaluate the efficacy of adding the mitochondrial oxidative phosphorylation inhibitor S-Gboxin (OXPHOS) to standard treatment for glioblastoma multiforme or glioma. Subjects will start oral S-gboxin orally twice daily and will evaluate the patients and vital status if they tolerate this dose at 3, 7and 15 days after initiation. Patients will undergo MRI scans before treatment and then at multiple time points during their participation in this Clinical Trial to monitor early tumor response to treatment ( MRI dates will be scheduled by the clinical trial coordinator) Peripheral blood samples will be collected at baseline, days 1-7-15-28-36-72 to compare biological indicators of treatment response. In some cases, circulating tumor cells (CTCs) will be monitored by real-time qRT-PCR to correlate with clinical data. Patients will also be assessed for the side effects they experience. Disease-free and overall survival outcomes will be recorded. Patients will also have their depressive symptoms, quality of life, and neurocognitive function assessed at multiple time points during and after treatment. After completion of the study, patients will be followed up at 3 months.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Glioblastoma Multiforme

Interventions

S-GboxinBIOLOGICAL

Gboxin specifically inhibits the growth of human glioblastoma cells but not normal cells. Gboxin rapidly and irreversibly impairs oxygen consumption in glioblastoma cells. Its positive charge for binding to mitochondrial oxidative phosphorylation complexes is dependent on the proton gradient of the inner mitochondrial membrane, and it inhibits F 0 F 1 ATP synthase activity in tumor cells. S-Gboxin crosses the blood-brain barrier at therapeutically effective concentrations.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

Inclusion Criteria: * confirmed diagnosis of Glioblastoma according to RANO criteria by contrast-enhanced MRI or PET-CT (including diffuse midline glioma, gliosarcoma or giant cell glioblastoma), relapse or disease progression * patient is able to understand and give consent to participate in the study * Karnofsky performance score ≥ 60 * women of childbearing potential must have a negative pregnancy test result no later than 7 days before registration Exclusion Criteria: * pregnant * known allergies * active treatment on annotner clinical trial * inability to complete with protocol or studio procedures.

Outcomes

Primary Outcomes

Brain tumor metabolism as measured by PET and MRI

The standardized uptake value (SUV) of HGG will be measured. SUV is a standard PET measurement. MRI with contrast will evaluate the change in tumor size before and after therapy S-Gboxin

Time frame: Up to 6 month

Secondary Outcomes

Overall survival (OS)

Kaplan-Meier survival estimates for OS will be presented with using Greenwood's formula at 12 months.

Time frame: Up to 12 month

Incidence of adverse events graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) version (v)4.03

The data will be organized by major organ system and MedDRA severity after completion of the Clinical Study.

Time frame: Up to 1 month after last dose of S-Gboxin