RESURGE - Randomized Controlled Comparative Phase II Trial on Surgery for Glioblastoma Recurrence
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 25
- 主要终点
- Overall survival from the date of inclusion
研究概览
简要总结
Patients with glioblastoma face a grim prognosis. Despite recent advancement in neurosurgical technology and neuro-oncology glioblastomas almost invariably progress or recur after a median of 4-8 months. The strategy to repeat tumor resection at recurrence in order to minimize tumor load and thus to facilitate subsequent second-line therapy has been shown to be feasible and safe.
However, evidence for a survival benefit of surgery for recurrent glioblastoma is scarce and relies entirely on retrospective analyses. While most retrospective analyses report an apparent survival benefit, an EORTC meta-analysis on second-line therapies found no survival difference in patients with or without surgery at recurrence. With regard to the risks and costs inherent to surgery for glioblastoma, a randomized controlled trial is required.
The purpose of the study is to compare the effect of craniotomy and tumor resection followed by adjuvant second-line therapy to no surgery followed by second-line therapy on overall survival, neurological status, and quality of life. Analysis of overall survival will be used to improve sample size estimation of a subsequent phase III trial for craniotomy and tumor resection of glioblastoma recurrence in cooperation with the EORTC.
详细描述
Background
Glioblastoma is a malignant, locally invasive brain tumor whose prognosis remains grim despite various intense treatment modalities. In the past, radical surgery was met with skepticism due to the aggressive infiltrative character of the tumor. However, an increasing number of retrospective studies over the last decade suggest a survival benefit for surgery. A recent post-hoc analysis of a randomized controlled trial on the use of the surgical adjunct 5-ALA reported a prolonged overall survival from 11.9 to 16.7 months (evidence level 2a) after more extensive resection. Thus, maximal safe resection has become a mainstay of treatment for newly diagnosed glioblastoma, followed by adjuvant radio-chemotherapy.
Glioblastoma almost invariably recurs after a median of 6.9 months, leaving but few options for further treatment. Recurrence of glioblastoma after surgery and concomitant adjuvant therapy represents an additional therapeutic challenge and may be treated with second-line pharmacotherapy. In addition, a second surgery may also be considered in highly selected patients.
The rationale for surgery - maximum safe resection - is to prolong survival through reduction of tumor load, and, maybe due to an increased efficacy of adjuvant treatment. However, surgery carries risks of complications, that may result in a decreased functional and survival outcome. The crucial question therefore is whether, to what extent, and at what costs in terms of neurological risks a second resection prolongs survival.
Objective
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •≥18 years of age
- •Prior resection of glioblastoma confirmed by histology
- •Glioblastoma pretreated with standard radiotherapy without or with temozolomide
- •First progression according to RANO criteria
- •First progression not within 3 months after completion of radiation therapy
- •Complete removal of contrast-enhancing lesion considered feasible without significant risk of permanent speech or motor function according to MRI as confirmed by study eligibility committee after screening and prior to recruitment
- •No encroachment of the M1 or A1 segments of the medial and anterior cerebral artery on MRI
- •No contrast enhancement in presumed speech and primary motor areas on MRI
- •No midline shift on MRI
- •No contrast enhancing ventricular spread, multifocal recurrence, meningeosis carcinomatosa or infiltration of the contra-lateral hemisphere on MRI
- •No contra-indication for surgery
- •Good functional status (KPS ≥ 70)
排除标准
- 未提供
研究组 & 干预措施
Surgery followed by adjuvant second-line therapy
Surgery followed by adjuvant second-line therapy
干预措施: Surgery followed by adjuvant second-line therapy (Procedure)
Second-line therapy alone
Second-line therapy alone
干预措施: Second-line therapy alone (Procedure)
结局指标
主要结局
Overall survival from the date of inclusion
时间窗: From the date of inclusion until death/end of study, assessed up to 5.7 years
次要结局
- Recruitment rate for all screened patients(Screening and inclusion)
- Total number of days spent at home after recurrence(From the date of inclusion until death/end of study, assessed up to 5.7 years)
- Morbidity of surgery(Every 3 months up to 2 years or until death, assessed up to 5.7 years)
- Total number of days spent outside home after recurrence(From the date of inclusion until death/end of study, assessed up to 5.7 years)
- Progression-free survival(From the date of inclusion until the date of objective progression or the date of patient's death, whichever occurs first, assessed up to 5.7 years)