NCT03463733: HUTMZ

Hydroxy-urea and Temozolomide in Patients With a Recurrent Malignant Brain Tumor (Glioblastoma)

Status unknown Phase 1 Last updated 8 October 2020

What this trial tests

Phase 1 trial testing Hydroxyurea in Glioma in 54 participants. Status unknown.

Timeline

2 March 2018

Primary endpoint
1 June 2021

1 June 2022

Quick facts

Lead sponsor	M.E. van Linde
Phase	Phase 1
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	54
Start date	2 March 2018
Primary completion	1 June 2021
Estimated completion	1 June 2022
Sites	1 location across Netherlands

Drugs / interventions tested

• Hydroxyurea — full drug profile →
• Temozolomide (temozolomide) — full drug profile →

Conditions studied

• Glioma — all drugs for Glioma →
• Glioblastoma — all drugs for Glioblastoma →

Sponsor

M.E. van Linde

Who can join

Eligibility, any sex, with Glioma or Glioblastoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Background

Currently, no standard treatment exists for patients with recurrent glioblastoma multiforme (rGBM) and used 2nd line treatments have low (up to max. 20%) response rates and very modest response duration (months). The median overall survival for GBM patients is 12-14 months from the time of diagnosis; therefore the development of new therapeutic options is imperative. HU has been used to treat hematological diseases and solid tumors (such as melanoma, ovarian, squamous cell carcinoma, head and neck carcinoma and brain tumors) in combination with other anti-cancer agents, but never with TMZ. If found safe, HU+TMZ, is easily translated to the clinic.

Purpose: Phase I trial to identify the maximum tolerated dose (MTD) for the combination of dose intense temozolomide (TMZ) and hydroxy-urea (HU) in (maximal) thirty patients with recurrent glioblastoma (rGBM).

Plan of investigation:

Month 0-24 (1st and 2nd year): Inclusion and follow-up of a maximum of 30 patients with rGBM

Month 25-31 (3rd year): Follow-up of patients included in the trial, data analysis (determining MTD and explorative analysis) and manuscript preparation.

Possible results:

1. Obtaining MTD and safety profile of daily HU+TMZ in patients with rGBM;
2. Preliminary data on the estimation of the median progression-free (PFS) and overall survival (OS), radiographic response proportion in patients with measurable disease, and exploratory correlation of treatment outcomes (PFS and OS) with o6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status in archival tumor specimens and further elucidation of underlying mechanism of re-sensitization of TMZ by HU. Exploratory analysis of biomarkers profile of platelets in patients treated with HU+TMZ.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Drug Repurposing, a Fast-Track Approach to Develop Effective Treatments for Glioblastoma.
   Ntafoulis I, Koolen SLW, Leenstra S, Lamfers MLM. · · 2022 · cited 23× · PMID 35954371 · DOI 10.3390/cancers14153705
2. Evolving Diagnostic and Treatment Strategies for Pediatric CNS Tumors: The Impact of Lipid Metabolism.
   Fernández-García P, Malet-Engra G, Torres M, Hanson D, et al · · 2023 · cited 5× · PMID 37239036 · DOI 10.3390/biomedicines11051365