protocolSection identificationModule nctId: NCT06279767, orgStudyIdInfo id: 2022-SR-557, briefTitle: Efficacy and Safety of TMZ Plus 6-MP in the Patients With Recurrent Glioblastoma, statusModule overallStatus: RECRUITING, startDateStruct date: 2022-07-01, primaryCompletionDateStruct date: 2025-07-01, completionDateStruct date: 2025-07-31, studyFirstPostDateStruct date: 2024-02-28, lastUpdatePostDateStruct date: 2024-02-28, sponsorCollaboratorsModule leadSponsor name: The First Affiliated Hospital with Nanjing Medical University, class: OTHER, descriptionModule briefSummary: 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., conditionsModule conditions: Glioblastoma, conditions: Cancer, conditions: Temozolomide, designModule studyType: INTERVENTIONAL, phases: PHASE1, phases: PHASE2, designInfo allocation: NA, interventionModel: SINGLE_GROUP, primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 27, type: ESTIMATED, armsInterventionsModule interventions name: 6-mercaptopurine, outcomesModule primaryOutcomes measure: PFS, secondaryOutcomes measure: OS, secondaryOutcomes measure: Safety evaluation, eligibilityModule sex: ALL, minimumAge: 18 Years, maximumAge: 65 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Department of Neurosurgery of The First Affiliated Hospital of Nanjing Medical University, status: RECRUITING, city: Nanjing, state: Jiangsu, zip: 210029, country: China, contacts name: Yongping You, PhD, role: CONTACT, phone: 13770694258, email: YYPL3@sohu.com, geoPoint lat: 32.06167, lon: 118.77778, hasResults: False