A Feasibility Assessment and a Phase I/II Trial of MLN518 for Treatment of Patients With Recurrent Glioblastoma
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)
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
After completion of study treatment, patients are followed every 2 months.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Feasibility defined as the ability of tandutinib to achieve a target tumor/plasma ratio >= 0.33 (Phase I)
Up to 4 years
National Cancer Institute (NCI)
United States: Food and Drug Administration
|Johns Hopkins University||Baltimore, Maryland 21205|
|Cleveland Clinic Foundation||Cleveland, Ohio 44195|
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|
|Massachusetts General Hospital Cancer Center||Boston, Massachusetts 02114|
|Henry Ford Hospital||Detroit, Michigan 48202|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|Massachusetts General Hospital||Boston, Massachusetts 02114-2617|
|University of Alabama at Birmingham||Birmingham, Alabama 35294-3300|
|Emory University||Atlanta, Georgia 30322|
|Wake Forest University Health Sciences||Winston-Salem, North Carolina 27157|
|Cleveland Clinic Cancer Center Independence||Independence, Ohio 44131|
|Adult Brain Tumor Consortium||Baltimore, Maryland 21231-1000|