Clinical trial NCT01285414: Verubulin, Radiation Therapy, and Temozolomide to Treat Patients With Newly Diagnosed Glioblastoma Multiforme
Official title: A Phase 2 Study of Verubulin With Radiation Therapy and Temozolomide in Subjects Newly Diagnosed With Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma Multiforme
Keywords: Glioblastoma
Brain Neoplasms
Brain Cancer
Verubulin
Lead sponsor: Myrexis Inc.
Sponsor class: INDUSTRY
First posted: 2011-01-28
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Have histologically proven, newly diagnosed glioblastoma multiforme
2. Age ≥ 18 years and \< 70 years
3. Have an ECOG performance score of 0, 1, or 2, or KPS ≥ 70
4. Have adequate bone marrow function , liver function, and kidney function before starting therapy
5. Begin study therapy no more than 6 weeks after surgery or biopsy
6. Subjects that have had surgery must have an MRI ≤ 72 hours after surgery

Exclusion Criteria:

1. Have a carmustine implant (e.g., Gliadel® Wafer)
2. Have uncontrolled hypertension (SBP \> 140 mmHg or DBP \> 90 mmHg for more than 1 week)
3. 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)
4. Have Troponin-I or Troponin T at Screening visit elevated above the upper limit of the reference range of the local institution
5. Have an increasing steroid requirement, indicative of a rapidly progressive disease
6. Have evidence of new, active intra tumor hemorrhage ≥ CTCAE Grade 2
7. Have had prior cranial radiotherapy
8. Have history of stroke and/or transient ischemic attack within 2 years of screening
9. Have history of cardiovascular disease (e.g., angina, myocardial infarction, congestive heart failure, etc.) within 2 years of screening
10. Be pregnant or breast feeding
11. Have a history of hypersensitivity reaction to Cremophor® EL
12. Have a history of hypersensitivity reaction or intolerance to temozolomide or dacarbazine (DTIC)

Primary outcomes:
measure: Part A: Safety
timeFrame: 14 weeks
measure: Part B: 9 Mo Progression-free survival
timeFrame: 9 Month
Secondary outcomes:
measure: Part A: Pharmacokinetic Parameters
timeFrame: 18 weeks
measure: Part B: 6 Mo Progression Free Survival
timeFrame: 6 month
measure: Overall Survival
timeFrame: 18 months
measure: Part B: 12 Mo Progression Free Survival
timeFrame: 12 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
Study officials:
affiliation: Myrexis Inc.
name: Andrew Beelen, MD
role: STUDY_DIRECTOR
References:
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citation: Kasibhatla S, Baichwal V, Cai SX, Roth B, Skvortsova I, Skvortsov S, Lukas P, English NM, Sirisoma N, Drewe J, Pervin A, Tseng B, Carlson RO, Pleiman CM. MPC-6827: a small-molecule inhibitor of microtubule formation that is not a substrate for multidrug resistance pumps. Cancer Res. 2007 Jun 15;67(12):5865-71. doi: 10.1158/0008-5472.CAN-07-0127.
citation: Tsimberidou AM, Akerley W, Schabel MC, Hong DS, Uehara C, Chhabra A, Warren T, Mather GG, Evans BA, Woodland DP, Swabb EA, Kurzrock R. Phase I clinical trial of MPC-6827 (Azixa), a microtubule destabilizing agent, in patients with advanced cancer. Mol Cancer Ther. 2010 Dec;9(12):3410-9. doi: 10.1158/1535-7163.MCT-10-0516.