Verubulin, Radiation Therapy, and Temozolomide to Treat Patients With Newly Diagnosed Glioblastoma Multiforme

Study Overview
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Brief Summary
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This, international, multi-center, Phase 2 study of verubulin will be conducted in patients with newly diagnosed Glioblastoma Multiforme (GBM). The study will be conducted in two parts. Part A is an open-label dose finding study that will determine the safety and tolerability of verubulin in combination with standard treatment. Part B is a randomized open-label study that will investigate progression-free survival and overall survival of patients receiving verubulin, at the dose determined in Part A, in combination with standard treatment versus standard treatment alone.

Official Title
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A Phase 2 Study of Verubulin With Radiation Therapy and Temozolomide in Subjects Newly Diagnosed With Glioblastoma Multiforme

Conditions
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Glioblastoma Multiforme

Intervention / Treatment
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* Drug: Verubulin
* Drug: Temozolomide & Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have histologically proven, newly diagnosed glioblastoma multiforme Age ≥ 18 years and < 70 years Have an ECOG performance score of 0, 1, or 2, or KPS ≥ 70 Have adequate bone marrow function , liver function, and kidney function before starting therapy Begin study therapy no more than 6 weeks after surgery or biopsy Subjects that have had surgery must have an MRI ≤ 72 hours after surgery Exclusion Criteria: Have a carmustine implant (e.g., Gliadel® Wafer) Have uncontrolled hypertension (SBP > 140 mmHg or DBP > 90 mmHg for more than 1 week) Have a left ventricular ejection fraction below the lower limit of the reference range for the institution, as measured by multiple gated acquisition (MUGA) or echocardiogram (ECHO) Have Troponin-I or Troponin T at Screening visit elevated above the upper limit of the reference range of the local institution Have an increasing steroid requirement, indicative of a rapidly progressive disease Have evidence of new, active intra tumor hemorrhage ≥ CTCAE Grade 2 Have had prior cranial radiotherapy Have history of stroke and/or transient ischemic attack within 2 years of screening Have history of cardiovascular disease (e.g., angina, myocardial infarction, congestive heart failure, etc.) within 2 years of screening Be pregnant or breast feeding Have a history of hypersensitivity reaction to Cremophor® EL Have a history of hypersensitivity reaction or intolerance to temozolomide or dacarbazine (DTIC)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Verubulin & standard of care (RT & TMZ)<br>Verubulin, at the dose selected in Part A, plus standard of care Radiation Therapy and Temozolomide | Drug: Verubulin<br>* Verubulin, dose determined in Part A, i.v. once weekly, Temozolomide & Radiation Therapy<br>* Other names: MPC-6827;|
| Active Comparator: Standard of care (RT & TMZ)<br>Standard of care Radiation Therapy and Temozolomide | Drug: Temozolomide & Radiation Therapy<br>* Temozolomide & Radiation Therapy<br>* Other names: Radiotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Safety | Assess the number and percentage of subjects with adverse events, abnormal laboratory parameters, and ECG changes as measures of safety and tolerability. | 14 weeks | 
| Part B: 9 Mo Progression-free survival |  | 9 Month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Pharmacokinetic Parameters | Measure the amount of verubulin in the body at specific time points when given with standard of care Radiation Therapy and Temozolomide | 18 weeks | 
| Part B: 6 Mo Progression Free Survival | Assess 6-month progression-free survival and compare median progression-free survival time for Radiation Therapy plus Temozolomide (TMZ)plus verubulin to standard of care (Radiation Therapy plus TMZ alone) | 6 month | 
| Overall Survival | Assess overall survival and compare median overall survival time for Radiation Therapy plus Temozolomide (TMZ)plus verubulin to standard of care (Radiation Therapy plus TMZ alone) | 18 months | 
| Part B: 12 Mo Progression Free Survival | Assess 12-month progression-free survival and compare median progression-free survival time for Radiation Therapy plus Temozolomide (TMZ)plus verubulin to standard of care (Radiation Therapy plus TMZ alone) | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glioblastoma, Brain Neoplasms, Brain Cancer, Verubulin