NCT03463733

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

International Multicenter Phase I Trial of Hydroxyurea in Combination With Dose-Intense Temozolomide in Recurrent Glioblastoma

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 54 (estimated)
• Sponsor: M.E. van Linde · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

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.

Conditions

• Glioma
• Glioblastoma

Interventions

Type	Name	Description
DRUG	Hydroxyurea	147-94-4/HYDROXYCARBAMIDE/HYDROXYCARBAMIDE/based on myeloproliferative disorders (MPD) record: SUB08076MIG
DRUG	Temozolomide	85622-93-1 /TEMOZOLOMIDE/TEMOZOLOMIDE/based on myeloproliferative disorders (MPD) record: SUB10889MIG

Timeline

• Start date: 2018-03-02
• Primary completion: 2021-06-01
• Completion: 2022-06-01
• First posted: 2018-03-13
• Last updated: 2020-10-08

Locations

1 site across 1 country: Netherlands

Regulatory

• FDA-regulated drug study