NCT06279767

Efficacy and Safety of TMZ Plus 6-MP in the Patients With Recurrent Glioblastoma

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Sponsor: The First Affiliated Hospital with Nanjing Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Glioblastoma, the most prevalent malignant tumor in the central nervous system, is characterized by high invasiveness and a propensity to recur, contributing to a relatively elevated mortality rate. Patients diagnosed with high-grade glioblastomas typically experience a median survival period of less than 14 months. Presently, the standard treatment for glioblastoma involves surgical resection combined with postoperative radiotherapy and chemotherapy, with postoperative chemotherapy playing a pivotal role in enhancing patient prognosis. Temozolomide (TMZ), a cutting-edge oral alkylating agent known for its advantageous properties, including easy traversal of the blood-brain barrier, induces DNA alkylation in tumor cells, fostering apoptosis. Currently, it serves as a frontline medication for postoperative chemotherapy in glioblastoma. However, clinical resistance to TMZ chemotherapy significantly hampers its efficacy in later stages. We have recently discovered and validated that 5-aminoimidazole-4-carboxamide (AICA), derived from TMZ, can transform into 5-aminoimidazole-4-carboxamide ribonucleotide-5-phosphate (AICAR) in GBM cells. Hypoxanthine phosphoribosyltransferase 1 (HPRT1) has been identified as the catalyst for the AICA reaction, generating AICAR. AICAR acts as an endogenous activator of AMP-activated protein kinase (AMPK), fostering chemoresistance in glioblastoma through the activation of the AMPK signaling pathway. 6-mercaptopurine (6-MP) competes effectively to inhibit HPRT1 activity, thereby impeding TMZ-induced AMPK activation and significantly heightening glioblastoma cell sensitivity to TMZ. In this project, we propose an innovative strategy involving the combination of 6-MP with TMZ for the treatment of glioblastoma.

Conditions

• Glioblastoma
• Cancer
• Temozolomide

Interventions

Type	Name	Description
DRUG	6-mercaptopurine	6-mercaptopurine (6-MP) is a crucial drug in the maintenance phase of acute lymphoblastic leukemia treatment.

Timeline

• Start date: 2022-07-01
• Primary completion: 2025-07-01
• Completion: 2025-07-31
• First posted: 2024-02-28
• Last updated: 2024-02-28

Locations

1 site across 1 country: China

Regulatory

• FDA-regulated drug study