Hydroxy-urea and Temozolomide in Patients With a Recurrent Malignant Brain Tumor (Glioblastoma) (HUTMZ)
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|ClinicalTrials.gov Identifier: NCT03463733|
Recruitment Status : Recruiting
First Posted : March 13, 2018
Last Update Posted : August 29, 2019
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.
- Obtaining MTD and safety profile of daily HU+TMZ in patients with rGBM;
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Glioma Glioblastoma||Drug: Hydroxyurea Drug: Temozolomide||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||54 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||International Multicenter Phase I Trial of Hydroxyurea in Combination With Dose-Intense Temozolomide in Recurrent Glioblastoma|
|Actual Study Start Date :||March 2, 2018|
|Estimated Primary Completion Date :||June 1, 2021|
|Estimated Study Completion Date :||June 1, 2022|
Experimental: Daily hydroxyurea and temozolomide
Hydroxyurea and temozolomide will be administered every 4 weeks, with 28 consecutive days defined as a treatment cycle. Treatment will be administered on an outpatient basis. Oral hydroxyurea (dose specified by the Dose Cohort below) and oral temozolomide (50 mg/m2/day) will be administered daily in 28-day cycles for 12 cycles or until unacceptable toxicity, intolerance, progressive disease, or withdrawal of consent. Patients will be treated in dose cohorts of 3 with each cohort receiving a specific daily dose assignment of hydroxyurea.
All patients in the study will receive temozolomide at 50 mg/m2/day ("dose-intense" schedule). The starting dose level for hydroxyurea will be 200 mg daily (QD) up to a maximum of 2000mg hydroxyurea a day.
147-94-4/HYDROXYCARBAMIDE/HYDROXYCARBAMIDE/based on myeloproliferative disorders (MPD) record: SUB08076MIG
Other Name: Hydroxycarbamide
85622-93-1 /TEMOZOLOMIDE/TEMOZOLOMIDE/based on myeloproliferative disorders (MPD) record: SUB10889MIG
Other Name: Temodar
- Maximal tolerated dose (MTD) hydroxyurea in combination with dose intense temozolomide [ Time Frame: 12 months ]MTD
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03463733
|Contact: Jelle Arts||+31 (0)20 firstname.lastname@example.org|
|VU University Medical Center||Recruiting|
|Amsterdam, Noord-Holland, Netherlands, 1081 HV|
|Contact: M.E. van Linde, MD +31 (0)20 4444321 email@example.com|
|Principal Investigator:||ME van Linde, MD||VU University Medical Center|