Efficacy and Tolerability of Cisplatin Plus Alternating Weekly Temozolomide in Recurrent High-grade Gliomas: A Single-arm Prospective Phase II Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 1
- 主要终点
- progression free survival (PFS)
研究概览
简要总结
Currently, the prognosis of recurrent high-grade gliomas is still dismal with no standard treatment protocol established. Cisplatin (CDDP), recommended by National Comprehensive Cancer Network (NCCN) as a chemotherapeutic agent in salvage treatment for recurrent high-grade gliomas, was shown to reduce O6-alkylguanine DNA-alkyl transferase (AGAT) activity and potentially capable of enhancing the antitumor effects of temozolomide (TMZ). Compared to the standard 5-day TMZ regimen, alternating weekly regimen that deliver more prolonged exposure of TMZ may lead to higher cumulative doses, and may deplete more O6-methylguanine DNA methyltransferase (MGMT), thus reducing the resistance of tumor cells to TMZ.
The investigators therefore initiate a single-arm Phase II study to evaluate the efficacy and tolerability of CDDP plus alternating weekly TMZ regimen in patients with recurrent high-grade gliomas.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological diagnosis of primary tumor as high-grade gliomas (WHO III or IV)
- •All patients should complete radiation therapy for primary gliomas.
- •MRI showed unequivocal evidence of tumor recurrence or progression.
- •The time to be enrolled should be more than 90 days after the radiation therapy.
- •Written informed consent
- •Eastern Cooperative Oncology Group(ECOG) score: 0-2
- •The patients with recurrent gliomas were treated without dose-dense TMZ therapy before enrollment.
- •Surgical interventions for recurrent gliomas are permitted and patients with no residual tumor are permitted
排除标准
- •Abnormal function of liver or renal (value more than 1.5 fold normal upper limit)
- •Blood routing: Hb < 90g/L, absolute neutrophil count≤1.5*10^9/L, platelet < 100*10^9/L
- •Pregnant or lactating women
- •Allergic to administered drugs
- •Radiation therapy in the previous 90 days before enrollment
- •The patients with recurrent gliomas were treated with dose-dense TMZ therapy before enrollment.
- •Acute infection in need of antibiotics intravenously
- •Participation in other clinical trials in the 90 days before enrollment
研究组 & 干预措施
CDDP plus Temozolomide
Patients were treated with CDDP and TMZ. CDDP was administered iv from Day 1 to 3 with everyday dose of 30mg. TMZ was orally administered from Day 1 to 7 and Day 15 to 21, with everyday dose of 125mg/m2 (Level 2). The period of one chemotherapy cycle is 28 days. TMZ dose levels were listed in Table 1.
Table 1 TMZ dose levels Dose levels Daily TMZ dose( mg/m2/d ) TMZ dose per cycle(mg/m2)
- 150 2100
- 125 1750
- 100 1400
- 75 1050
干预措施: CDDP (Drug)
CDDP plus Temozolomide
Patients were treated with CDDP and TMZ. CDDP was administered iv from Day 1 to 3 with everyday dose of 30mg. TMZ was orally administered from Day 1 to 7 and Day 15 to 21, with everyday dose of 125mg/m2 (Level 2). The period of one chemotherapy cycle is 28 days. TMZ dose levels were listed in Table 1.
Table 1 TMZ dose levels Dose levels Daily TMZ dose( mg/m2/d ) TMZ dose per cycle(mg/m2)
- 150 2100
- 125 1750
- 100 1400
- 75 1050
干预措施: Temozolomide (Drug)
结局指标
主要结局
progression free survival (PFS)
时间窗: at 6 months
次要结局
- overall survival(OS)(at 1 year and 2 years)