Verubulin, Radiation Therapy, and Temozolomide to Treat Patients With Newly Diagnosed Glioblastoma Multiforme - Full Text View

Purpose

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.

Condition	Intervention	Phase
Glioblastoma Multiforme	Drug: Verubulin Drug: Temozolomide & Radiation Therapy	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 2 Study of Verubulin With Radiation Therapy and Temozolomide in Subjects Newly Diagnosed With Glioblastoma Multiforme

Resource links provided by NLM:

MedlinePlus related topics: Brain Cancer Cancer

Drug Information available for: Temozolomide

U.S. FDA Resources

Further study details as provided by Myrexis Inc.:

Primary Outcome Measures:

Part A: Safety [ Time Frame: 14 weeks ] [ Designated as safety issue: Yes ]
Assess the number and percentage of subjects with adverse events, abnormal laboratory parameters, and ECG changes as measures of safety and tolerability.
Part B: 9 Mo Progression-free survival [ Time Frame: 9 Month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Part A: Pharmacokinetic Parameters [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
Measure the amount of verubulin in the body at specific time points when given with standard of care Radiation Therapy and Temozolomide
Part B: 6 Mo Progression Free Survival [ Time Frame: 6 month ] [ Designated as safety issue: No ]
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)
Overall Survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
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)
Part B: 12 Mo Progression Free Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
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)

Enrollment:	5
Study Start Date:	December 2010
Study Completion Date:	March 2012
Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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: Azixa MPC-6827
Active Comparator: Standard of care (RT & TMZ) Standard of care Radiation Therapy and Temozolomide	Drug: Temozolomide & Radiation Therapy Temozolomide & Radiation Therapy Other Names: Temodar TMZ Radiotherapy

Eligibility

Ages Eligible for Study:	18 Years to 69 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01285414

Locations

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

Sponsors and Collaborators

Myrexis Inc.

Investigators

Study Director:

Andrew Beelen, MD

Myrexis Inc.

More Information

Additional Information:

Additional Information This link exits the ClinicalTrials.gov site

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.

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.

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.

Responsible Party:	Myrexis Inc.
ClinicalTrials.gov Identifier:	NCT01285414 History of Changes
Other Study ID Numbers:	MPC-6827-021
Study First Received:	January 14, 2011
Last Updated:	April 10, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Myrexis Inc.:

Glioblastoma
Brain Neoplasms
Brain Cancer
Verubulin

Additional relevant MeSH terms:

Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 17, 2013