Tandutinib in Treating Patients With Recurrent or Progressive Glioblastoma

Adult Glioblastoma Clinical Trial

Official title: A Feasibility Assessment and a Phase I/II Trial of MLN518 for Treatment of Patients With Recurrent Glioblastoma

Status Completed

Clinical Trial Summary

This phase I/II trial is studying the side effects and best dose of tandutinib and to see how well it works in treating patients with recurrent or progressive glioblastoma.Tandutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Assess the ability of tandutinib to achieve a target tumor/plasma ratio ≥ 0.33 in patients with recurrent glioblastoma undergoing resection. (Feasibility study) II. Detect potential biological effects of tandutinib by measuring platelet-derived growth factor receptor phosphorylation status and downstream activation of Akt and Erk. (Feasibility study) III. Determine the maximum tolerated dose of tandutinib in patients with recurrent or progressive glioblastoma. (Phase I) IV. Estimate the frequency of toxicities associated with tandutinib in patients with recurrent or progressive glioblastoma. (Phase I) V. Describe the pharmacokinetics of this route of administration in patients with recurrent or progressive glioblastoma. (Phase I) VI. Assess tumor response rate in patients with recurrent or progressive glioblastoma. (Phase II)

SECONDARY OBJECTIVES:

I. Estimate overall survival of patients with recurrent or progressive glioblastoma. (Phase II) II. Estimate the 6-month progression-free survival rate in these patients. (Phase II) III. Assess the toxicities associated with tandutinib in these patients. (Phase II) IV. Assess the pharmacokinetic profile of this route of administration in these patients. (Phase II) V. Explore protein-expression patterns that distinguish patients who respond to therapy from those who do not. (Phase II)

OUTLINE: This is a multicenter, prospective, nonrandomized, feasibility study and phase I study (in parallel) followed by an open label phase II study.

FEASIBILITY STUDY: Patients receive oral tandutinib twice daily for 7 days. Patients then undergo biopsy or surgery to remove the tumor. Within 2 weeks after biopsy or surgery, patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE I: Patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of tandutinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

[Note: *On day 1 of course 1, patients receive only 1 dose of tandutinib.]

PHASE II: Patients receive tandutinib as in phase I at the MTD determined in phase I.

Patients undergo blood sample collection for pharmacokinetic studies. Patients in the feasibility portion of the study also undergo blood and tissue sample collection for correlative studies by mass spectrometry for tandutinib concentration. Samples are also examined for circulating endothelial cells and plasma proteins (vascular endothelial growth factor [VEGF]-A, -B, -C, and -D, soluble VEGF receptors [sVEGFR's], placental growth factor [P1GF], platelet-derived growth factor [PDGF]-AA, PDGF-AB, PDGF-BB, angiopoietin-1 and -2, tumstatin, thrombospondin-1, and IL-8) as potential markers of the antiangiogenic effect of tandutinib.

After completion of study treatment, patients are followed every 2 months. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adult Brain Tumor
• Adult Giant Cell Glioblastoma
• Adult Glioblastoma
• Adult Gliosarcoma
• Brain Neoplasms
• Glioblastoma
• Gliosarcoma
• Recurrent Adult Brain Tumor

• NCT number: NCT00379080
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 2007