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

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

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.

Study Overview

• Status: Completed
• Conditions: Glioblastoma Multiforme
• Intervention / Treatment: Drug: Verubulin; Drug: Temozolomide & Radiation Therapy

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Myrexis Inc.

Publications and helpful links

General Publications

• Sirisoma N, Pervin A, Zhang H, Jiang S, Willardsen JA, Anderson MB, Mather G, Pleiman CM, Kasibhatla S, Tseng B, Drewe J, Cai SX. Discovery of N-(4-methoxyphenyl)-N,2-dimethylquinazolin-4-amine, a potent apoptosis inducer and efficacious anticancer agent with high blood brain barrier penetration. J Med Chem. 2009 Apr 23;52(8):2341-51. doi: 10.1021/jm801315b.
• 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.
• 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.

Helpful Links

• Additional Information

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: January 14, 2011
• First Submitted That Met QC Criteria: January 26, 2011
• First Posted (Estimate): January 28, 2011

Study Record Updates

• Last Update Posted (Estimate): April 11, 2012
• Last Update Submitted That Met QC Criteria: April 10, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Glioblastoma; Brain Cancer; Brain Neoplasms; Verubulin
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: MPC-6827-021