brain tumor High grade glioma
Conditions
Interventions
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
Sponsors
Vrije Universiteit Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Histologically or cytologically confirmed glioblastoma multiforme Patients may have had any number of prior therapies for glioblastoma. Patients must be at least 28 days from any investigational agent, 28 days from prior cytotoxic therapy (except 23 days from prior temozolomide, 14 days from vincristine, 42 days from nitrosoureas, 21 days from procarbazine administration), and 7 days for patients who received metronomic chemotherapy or non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. Age >=18 years en mentally competent Karnofsky Performance Status (KPS) >=60% Participants must have normal organ and marrow function as defined below (leukocytes >=3,000/mcL, absolute neutrophil count >=1,500/mcL, platelets >=100,000/mcL, total bilirubin within normal institutional limits, AST(SGOT)/ALT(SGPT) =60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal) Progressive disease on contrast-enhanced brain CT or MRI as defined by RANO
Exclusion criteria
Exclusion criteria: Participants who are receiving any other investigational agents or devices in investigation for glioblastoma. No previous treatment with an anti-VEGF inhibitor. History of allergic reactions attributed to compounds of similar chemical composition to temozolomide and/or hydroxyurea. Uncontrolled intercurrent illness including, that would limit compliance with study requirements. Pregnant women HIV-positive participants on combination antiretroviral therapy Patients with a history of a different malignancy are ineligible except for the following circumstances: if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; patients with treated cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin. Patients will not be eligible if they have evidence of other malignancy requiring therapy other than surgery within the last 3 years. Major surgery within 2 weeks of start of study drug; or not fully recovered from any side effects of previous procedures. Presence of extra-cranial metastatic disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Objective: To determine the maximimum tolerated dose (MTD) and safety profile of daily hydroxyurea in combination with continuous dose-intense temozolomide (50 mg/m2/day) in patients with recurrent GBM. If 1 of 3 patients develops DLT during the first 8 weeks of treatment that Dose Cohort will be expanded by 3 additional patients at the same dose level. The 3 additional patients must be followed for at least 8 weeks and toxicity must be evaluated before continuing escalation. If no additional DLT are observed (i.e. 1/6 DLT total in the expanded Dose Cohort) then 3 new patients may be entered at the next highest dose level. However, if 1/3 patients experience DLT in this expanded cohort (i.e. 2/6 DLT total in the expanded Dose Cohort) then this will be declared the MTD. If 2/3 or 3/6 patients experience DLT at any dose level (above dose level -1) then the next cohort of 3 patients will be treated at a dose one level lower than the dose at which 2/3 DLT were observed. All of the above holds for DLT attributed to hydroxyurea. The dose of hydroxyurea in combination with temozolomide will not be escalated above 2000 mg QD, the maximum daily dose when used in monotherapy for other malignancies such as resistant chronic myelocytic leukemia. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Objectives: • To estimate the preliminary median progression-free survival of patients with recurrent glioblastoma treated with daily hydroxyurea in combination with dose-intense temozolomide. • To estimate the preliminary radiographic response proportion in patients with measurable disease. • To estimate the preliminary median overall survival. • Exploratory correlation of treatment outcomes (progression-free and overall survival with MGMT promoter methylation status in archival tumor specimens. | — |
Countries
Netherlands
Outcome results
None listed