Recurrent WHO Grade 2 Glioma Clinical Trial
Official title:
A Phase 1 Adaptive Dose Escalation With Dose Expansion Study of Triapine in Combination With Temozolomide (TMZ) for Patients With Recurrent Glioblastoma
This phase I trial tests the safety, side effects, and best dose of triapine in combination with temozolomide in treating patients with glioblastoma that has come back after a period of improvement (recurrent). Triapine inhibits an enzyme responsible for producing molecules required for the production of deoxyribonucleic acid (DNA), which may inhibit tumor cell growth. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill tumor cells and slow down or stop tumor growth. Giving triapine in combination with temozolomide may be safe, tolerable, and/or effective in treating patients with recurrent glioblastoma.
PRIMARY OBJECTIVE: I. To evaluate the recommended phase 2 dose (RP2D) for triapine (3-AP) in combination with temozolomide (TMZ). SECONDARY OBJECTIVES: I. To evaluate the safety profile of triapine in combination with temozolomide (TMZ). II. To evaluate progression-free survival (PFS). III. To evaluate overall survival (OS). IV. To evaluate the overall response rate (ORR) per Response Assessment in Neuro-Oncology (RANO) criteria. EXPLORATORY OBJECTIVES: I. To investigate the distribution of triapine within tumor and peritumoral areas post oral administration and correlation with serum levels. II. To investigate the potential interaction of drug absorption when administrating oral triapine and temozolomide together by measuring plasma levels triapine and temozolomide post administration. III. To evaluate oral triapine plasma pharmacokinetics and corresponding methemoglobin level by venous blood gas proportion. IV. To evaluate the quality of life per Functional Assessment of Cancer Therapy-Brain (FACT-Br) for patients treated with triapine and temozolomide. OUTLINE: This is a dose-escalation study of triapine in combination with temozolomide. Patients with recurrent glioblastoma not planning to undergo surgery are assigned to group 1 or group 2. Patients with recurrent glioblastoma planning to undergo surgery are assigned to group 3. GROUPS 1 AND 2: Patients receive temozolomide orally (PO) once daily (QD) and triapine PO QD on days 1-5 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI) at screening and on study and undergo collection of blood samples on study. GROUP 3: Patients receive triapine PO QD for 5 days prior to surgical resection. After surgical resection, patients receive temozolomide PO QD and triapine PO QD on days 1-5 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI at screening and on study and undergo collection of blood samples on study. After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 24 months. ;