Randomized Phase II Non-Inferiority Study of 5-Day Versus 1-Day RAPid SimPLE (RAPPLE) Targeted Radiation Treatment for Brain Metastases
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 9
- 主要终点
- Survival Time
研究概览
简要总结
The aim of the study is to show that rapid, simple targeted radiotherapy to brain metastases with 8 Gy / 1 is non-inferior to 20 Gy / 5 in terms of overall survival for patients with poor prognosis.
详细描述
Hypothesis For selected patients with limited life expectancy, a single targeted fraction of 8 Gy / 1 to brain metastases will provide equivalent survival as targeted radiotherapy with 20 Gy / 5 to brain metastases.
Justification The QUARTZ study randomized patients with brain metastases and poor prognosis between 20 Gy / 5 whole brain radiotherapy (WBRT) and best supportive care. The median survival in both arms of the study was 9 weeks. The quality of life in both arm was also the same. It is known that WBRT significantly diminishes quality of life. The investigators interpretation of the QUARTZ trial is that the unchecked growth of brain metastases in the best supportive care arm diminishes quality of life as much as WBRT. To control brain metastases without giving WBRT, targeted treatment with 20 Gy / 5 to the metastases alone is standard care at BC Cancer. Numerous randomized trials have compared the efficacy of 20-30 Gy / 5-10 fractions and 8 Gy / 1 for palliative treatment of pain from bone metastases. In addition, there is a randomized trial showing that 20 Gy / 5 and 8 Gy /1 are equally effective for the treatment of symptoms from spinal cord compression. This study will test the use of this shorter, one-visit treatment schedule against the standard 5-visit treatment schedule for patients with brain metastases.
Research Design Randomized Phase II Non-Inferiority Study. The estimated median survival for this cohort, based upon a prior cohort study from 2012-2016 at BC Cancer is 3 months (13 weeks). The investigators would regard a study median survival of less than the 9-week median survival observed in the QUARTZ trial as unacceptable. Hence, the hazard ratio for the experimental arm and the control arm is: 13 weeks / 9 weeks = 1.44. With one-sided Type I error set at alpha = 0.2 and power = 0.8, the investigators calculated a theoretical sample size of 86 patients. Based on prior experience with clinical trials for patients with brain metastases, a 15% risk of drop-out and loss to follow up is expected. Hence the final sample size will be 100 patients. Stratification by the diagnosis-specific graded prognostic assessment (DS-GPA) ranges of 0.0 - 1.0 and 1.5 - 2.0 and lung cancer versus other histologies will help to ensure baseline characteristics that predict for equal survival are equally distributed in both arms of the study.
Statistical Analysis The primary endpoint is overall survival. The study will be considered to be a positive phase II non-inferiority study if the median survival in the experimental arm is within 4 weeks of the median survival in the standard arm.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must meet all of the following criteria to be eligible for participation in this study:
- •Pathological diagnosis of a non-hematopoietic malignancy
- •Brain metastases of any size
- •Any number of untreated or progressing, previously treated brain metastases that can all be contoured and targeted
- •Presence of extracranial disease
- •Diagnosis-Specific Graded Prognostic Assessment ≤ 2.
- •(https://brainmetgpa.com/) or Graded Prognostic Assessment ≤ 2.0 (Appendix I)
- •Able to complete the EuroQOL (EQ-5D-5L) questionnaire
- •Willing and able to have regular imaging follow up
- •Feasible to start protocol treatment within 14 days of participant enrolment
- •Karnofsky Performance Score (KPS) ≥ 50
排除标准
- •Subjects are excluded from the study if any of the following criteria apply:
- •Inability to have a brain MRI
- •WBRT less than 3 months prior to randomization
- •Disseminated leptomeningeal carcinomatosis (limited pachymeningeal disease is permitted)
- •Multiple sclerosis
- •Neurologically declining despite corticosteroids
- •Appropriate for surgery or stereotactic radiosurgery
- •Germ cell and primary brain tumours
- •Systemic lupus erythematosis, scleroderma, or other connective tissue disorders not in remission
- •Any other serious intercurrent illness or medical condition judged by the local investigator to compromise the participant's safety, preclude safe administration of the planned protocol treatment, or prevent the participant from being managed according to the protocol guidelines
- •Pregnancy
- •Potentially fertile men or women of childbearing potential who are unwilling to employ highly effective contraception
结局指标
主要结局
Survival Time
时间窗: 1 year
The median time from randomization to death
次要结局
- Control of brain disease(1 year)
- Retreatments for brain metastases(1 year)
- Corticosteroid use(6 weeks)
- Health-Related Quality of Life(1 year)
- Median Time to Decline in Karnofsky Performance Status(1 year)
- Adverse Events(1 year)
- Control of treated brain metastases(1 year)