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

NCT01285414 | Completed Phase 2 DMC

• 1 other identifier: MPC-6827-021
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

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.

Conditions

Glioblastoma Multiforme

Keywords

Glioblastoma; Brain Neoplasms; Brain Cancer; Verubulin

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Part A: Pharmacokinetic Parameters

  18 weeks

• Part B: 6 Mo Progression Free Survival

  6 month

• Overall Survival

  18 months

• Part B: 12 Mo Progression Free Survival

  12 months

Study Arms (2)

Verubulin & standard of care (RT & TMZ)

EXPERIMENTAL

Verubulin, at the dose selected in Part A, plus standard of care Radiation Therapy and Temozolomide

Drug: Verubulin

Standard of care (RT & TMZ)

ACTIVE COMPARATOR

Standard of care Radiation Therapy and Temozolomide

Drug: Temozolomide & Radiation Therapy

Interventions

Verubulin DRUG

Verubulin, dose determined in Part A, i.v. once weekly, Temozolomide \& Radiation Therapy

Also known as: Azixa, MPC-6827

Verubulin & standard of care (RT & TMZ)

Temozolomide & Radiation Therapy DRUG

Temozolomide \& Radiation Therapy

Also known as: Temodar, TMZ, Radiotherapy

Standard of care (RT & TMZ)

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Myrexis Inc.: lead

Study Sites (2)

Stanford University

Stanford, California, 94305, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Related Publications (3)

• 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.

  PMID: 19296653 BACKGROUND

• 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.

  PMID: 17575155 BACKGROUND

• 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.

  PMID: 21159616 BACKGROUND

Related Links

• Additional Information

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

verubulin; Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• Andrew Beelen, MD

  Myrexis Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2011
• First Posted: January 28, 2011
• Study Start: December 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: April 11, 2012

Record last verified: 2012-04

Locations

US (2)