Efficacy and Safety of TMZ Plus 6-MP in the Patients With Recurrent Glioblastoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- PFS
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and 65, no gender restrictions.
- •Histologically confirmed glioblastoma as the primary tumor after surgery.
- •Patients with recurrent glioblastoma confirmed by MRI after standard treatment (surgery, Stupp regimen) failure, supported by RANO criteria evaluation.
- •At least one measurable intracranial tumor lesion according to RANO criteria.
- •No prior treatment with 6-mercaptopurine or similar drugs.
- •General condition assessed by Karnofsky Performance Status (KPS) score ≥
- •Normal bone marrow function: white blood cell count ≥ 3.5 × 10^9/L, neutrophil count ≥ 2.0 × 10^9/L, hemoglobin count ≥ 90 g/L, platelet count ≥ 80 × 10^9/L.
- •Normal organ functions such as heart and lung, and no severe internal diseases.
- •Willing to sign an informed consent form, good compliance, able to attend regular follow-ups, and voluntarily agree to comply with the study protocol.
排除标准
- •Participants who do not consent.
- •Vulnerable populations such as pregnant women, children, and adolescents.
- •No history of or concurrent malignancy within the past 5 years.
- •Abnormal liver function (total bilirubin > 1.5 times the upper limit of normal, ALT/AST > 2 times the upper limit of normal).
- •Impaired kidney function (serum creatinine > 1.5 times the upper limit of normal).
- •Presence of organic heart disease leading to clinical symptoms or cardiac dysfunction (NYHA ≥ Grade 2).
- •Factors significantly affecting oral drug absorption, such as difficulty swallowing, intestinal obstruction, etc.
研究组 & 干预措施
Treatment with a combination of 6-mercaptopurine and temozolomide
干预措施: 6-mercaptopurine (Drug)
结局指标
主要结局
PFS
时间窗: 12 months
Progression-free survival (PFS), defined as the time from treatment to progression or death, whichever occurs first
次要结局
- OS(12 months)
- Safety evaluation(12 months)