A Phase 1-2 Trial of Temozolomide and Hypofractionated Radiotherapy in Treatment of Supratentorial Glioblastoma Multiforme
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Number of Dose-limiting Toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to investigate the safety and effectiveness of a combination treatment for glioblastoma multiforme utilizing radiotherapy plus the FDA-approved chemotherapy drug temozolomide
详细描述
Primary Objective: To determine the maximum tolerated dose (MTD), based on acute CNS toxicity at 30 days, of hypofractionated radiotherapy given in 5 fractions with temozolomide for the treatment of glioblastoma multiforme.
Secondary Objectives:
- Assess the short- and long-term adverse effects.
- Determine the radiographic response rate.
- Determine the overall survival rate.
- Assess quality of life during treatment
To determine the maximum tolerated dose (MTD) of hypofractionated (5 fractions) radiotherapy with temozolomide for the treatment of glioblastoma multiforme, patients will be evaluated by a multi-disciplinary team composed of radiation oncologists, neurosurgeons, and neuro-oncologists to assess for their eligibility. Patient's oncologic history, presenting symptoms, physical examination, pathology, and imaging studies will be reviewed. Patients will be evaluated for surgical candidacy and resectability. Patients who are surgical candidates will undergo a surgical resection prior to radiotherapy. Patients whose tumors are unresectable or are not good surgical candidates will undergo a biopsy for tissue diagnosis. Radiation will be delivered in five fractions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Histopathologically confirmed newly diagnosed glioblastoma multiforme. Diagnosis must be made by surgical biopsy or excision
- •The tumor must be supratentorial in location
- •The planning target volume (tumor plus margin) must measure ≤ 150 cm^3 in volume
- •Age ≥ 18 years
- •Life expectancy of at least 12 weeks
- •Patient must have adequate organ function to tolerate temozolomide (details in the protocol)
排除标准
- •Patients who have previously been treated with brain irradiation to the region that would result in overlap of the radiation fields
- •Tumor foci detected below the tentorium
- •Multifocal disease or leptomeningeal spread
- •Prior allergic reaction to the study drugs involved in this protocol
- •Patients with pacemaker will be allowed to undergo CT instead of MRI
- •Pediatric patients (age < 18), pregnant women, and nursing patients will be excluded
研究组 & 干预措施
Stereotactic Radiosurgery (25 Gray x 5 fractions)+Temozolomide
Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³.
干预措施: Temozolomide (Drug)
Stereotactic Radiosurgery (25 Gray x 5 fractions)+Temozolomide
Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³.
干预措施: Stereotactic Radiosurgery (SRS) (Procedure)
Stereotactic Radiosurgery (30 Gray x 5 fractions)+Temozolomide
Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³.
干预措施: Temozolomide (Drug)
Stereotactic Radiosurgery (30 Gray x 5 fractions)+Temozolomide
Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³.
干预措施: Stereotactic Radiosurgery (SRS) (Procedure)
Stereotactic Radiosurgery (35 Gray x 5 fractions)+Temozolomide
Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³.
干预措施: Temozolomide (Drug)
Stereotactic Radiosurgery (35 Gray x 5 fractions)+Temozolomide
Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³.
干预措施: Stereotactic Radiosurgery (SRS) (Procedure)
Stereotactic Radiosurgery (40 Gray x 5 fractions)+Temozolomide
Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³.
干预措施: Temozolomide (Drug)
Stereotactic Radiosurgery (40 Gray x 5 fractions)+Temozolomide
Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³.
干预措施: Stereotactic Radiosurgery (SRS) (Procedure)
结局指标
主要结局
Number of Dose-limiting Toxicities (DLTs)
时间窗: 30 days
The maximum-tolerated dose (MTD) of study treatment (temozolomid plus hypofractionated radiotherapy administered as 5 fractions) is defined as either: * The highest radiation dose per protocol, or * The radiation dose at which dose-limiting toxicities (DLTs) occurred in ≥ 2 of 3 participants at a dose level, and/or ≥ 2 of 6 participants, at a dose level. Dose-limiting toxicity (DLT) was defined as a treatment-related (with possible, probable or definite attribution) Grade 3 to 5 CNS toxicity \[Common Terminology Criteria for Adverse Events (CTCAE) v4\] occurring within 30 days of stereotactic radiosurgery (SRS). The non-stratified outcome is reported as the number of DLTs observed in by radiation dose and by strata (Planning Target Volume (PTV) \< 60 cm³ and from 60 to 150 cm³).
次要结局
- Overall Survival (OS)(20 Months.)
- Progression-free Survival(18 Months.)
- Quality of Life by European Organisation for Research and Treatment of Cancer (EORTC-QLQ C30) Survey(12 Months)
- Quality of Life by MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) Survey(12 months)
- Number of Acute Toxicity Within 30 Days(30 days)
- Long-term Toxicity After More Than 30 Days(12 months)
- Percent of Participants With Radiographic Response(6 months)
- Treatment Failure Analysis(18 months)
- Quality of Life by Brain-20 Survey(12 months)
研究者
Scott Soltys
Assistant Professor of Radiation Oncology
Stanford University