NCT03452930

Tinostamustine With or Without Radiation Therapy in Treating Patients With Newly Diagnosed MGMT-Unmethylated Glioblastoma

A Phase I Study to Investigate the Safety, Pharmacokinetic Profile and the Efficacy of EDO-S101, a First-in-Class Alkylating HDACi Fusion Molecule in Patients With Newly Di-Agnosed MGMT-Promoter Unmethylated Glioblastoma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of tinostamustine (EDO-S101) given with or without radiation therapy in treating patients with newly diagnosed MGMT-unmethylated glioblastoma. Tinostamustine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth in patients with glioblastoma.

Detailed description

PRIMARY OBJECTIVES: I. To characterize the safety profile and determine the maximum tolerated dose (MTD) of tinostamustine (EDO-S101) in the adjuvant phase of therapy for patients with newly diagnosed MGMT-promoter unmethylated glioblastoma (GB) post chemoradiation with temozolomide. (Stage 1) II. To characterize the safety profile and determine the MTD of EDO-S101 when given as a single agent in the concomitant phase with radiation therapy (RT) in patients with newly diagnosed GB who are MGMT-promoter unmethylated. (Stage 2) III. To confirm the MTD of EDO-S101 in the concomitant phase and adjuvant phase in an expanded population of newly diagnosed GB patients who are MGMT-promoter un-methylated. (Dose Expansion Group) SECONDARY OBJECTIVE: I. To assess anti-tumor activity for patients with newly diagnosed GB who are MGMT-promoter unmethylated based on progression-free survival (PFS), overall survival (OS), and overall response rate (ORR). EXPLORATORY OBJECTIVE: I. Profiling tumor deoxyribonucleic acid (DNA), messenger ribonucleic acid (mRNA), microRNA and epigenetic profiling (DNA methylation) and evaluation of whole exome sequencing, RNA sequencing, microRNA sequencing and cell-free circulating tumor DNA (ctDNA) and correlate with outcome. OUTLINE: This is a dose-escalation study of tinostamustine. Patients are assigned to 1 of 2 stages. STAGE 1: Patients who have completed temozolomide (TMZ) and radiation therapy (RT) receive tinostamustine intravenously (IV) over 60 minutes on day 1. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. STAGE 2: Patients who have received no treatment other than surgery undergo RT 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive tinostamustine over 60 minutes IV on day 1. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 3 months.

Conditions

• Glioblastoma
• Gliosarcoma
• MGMT-Unmethylated Glioblastoma

Interventions

Type	Name	Description
RADIATION	Radiation Therapy	Undergo RT
DRUG	Tinostamustine	Given IV

Timeline

• Start date: 2018-08-13
• Primary completion: 2024-06-05
• Completion: 2024-06-05
• First posted: 2018-03-02
• Last updated: 2025-06-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study