Testing the Addition of an Anti-Cancer Drug, Triapine, to the Usual Radiation Therapy for Recurrent Glioblastoma or Astrocytoma

Description

PRIMARY OBJECTIVE:

I. To identify the safety and maximally tolerated dose (MTD) of oral triapine used in combination with radiation therapy for patients with recurrent glioblastoma (GBM) or astrocytoma.

SECONDARY OBJECTIVES:

I. To observe and record anti-tumor activity. II. To determine the pharmacokinetics of oral triapine in plasma and the central nervous system (CNS).

III. To evaluate the efficacy of triapine when administered in combination with radiation therapy by assessing:

IIIa. Progression-free survival (PFS); IIIb. Overall survival (OS); IIIc. The proportion of patients requiring bevacizumab for symptom control; IIId. The correlation of genetic mutations in select genes (e.g., p53, p16, KRAS, and Pi3k/mTOR/AKT) with tumor response and clinical outcomes.

OUTLINE: This is a dose-escalation study of triapine in combination with radiation therapy.

Patients undergo intensity-modulated radiation therapy (IMRT) once daily (QD) 5 days per week (Monday-Friday) for a total of 10 treatment days over 2 weeks and receive triapine orally (PO) 2 hours prior to IMRT on each radiation treatment day in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and/or magnetic resonance imaging (MRI) throughout the study as well as blood sample collection during screening and on study. Patients may undergo cerebrospinal fluid (CSF) sample collection during screening.

After completion of study treatment, patients are followed up at 2 weeks after radiation therapy, then every 3 months for up to 5 years from study treatment initiation.