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

Glioblastoma Multiforme Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01285414
• Other study ID #: MPC-6827-021
• Status: Completed
• Phase: Phase 2
• First received: January 14, 2011
• Last updated: April 10, 2012
• Start date: December 2010
• Est. completion date: March 2012

Study information

• Verified date: April 2012
• Source: Myrexis Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: March 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 69 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

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

Locations

Country	Name	City	State
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Stanford University	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Myrexis Inc.

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	Part B: 9 Mo Progression-free survival		9 Month	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

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