SCOPE2 - A Randomised Phase II/III Trial to Study Radiotherapy Dose Escalation in Patients With Oesophageal Cancer Treated With Definitive Chemo-radiation With an Embedded Phase II Trial for Patients With a Poor Early Response Using Positron Emission Tomography (PET)
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 584
- 试验地点
- 26
- 主要终点
- Primary endpoint phase in adenocarcinoma phase II comparing standard dose radiotherapy to high dose radiotherapy
研究概览
简要总结
Research has shown that increasing the dose of radiotherapy improves outcomes in patients with lung and head and neck cancers. This study aims to see whether this is also the case for patients with tumour of the oesophagus. This trial will compare the effects of the standard dose of radiotherapy to a higher dose whilst closely monitoring the side effects.
A comparison will also be made regarding the effects of the standard drugs used in chemotherapy (cisplatin and capecitabine) with an alternative combination (carboplatin and paclitaxel) in patients that do not show a response to chemotherapy with standard drugs early on in treatment.
All patients will receive 6 weeks of chemotherapy and 5 weeks of chemoradiotherapy.
How the study will be conducted:
Prior to the commencement of treatment each patient will have a special scan called a PET scan. Patients will receive a second PET scan two weeks after the start of standard chemotherapy. The changes between the two scans will then be used to allocate treatment into the different arms of the study. All study subjects will be randomised to receive either the standard radiotherapy dose or the high radiotherapy dose. The participants that do not respond to the first cycle of standard chemotherapy will be eligible to take part in the aspect of the trial looking at an alternative chemotherapy regimen. Patients will be randomised as follows;
On the basis of the second PET scan, patients who are not responding to standard chemotherapy will be allocated by a computer to one of the four groups detailed below:
- Standard chemotherapy and standard dose of radiotherapy
- Standard chemotherapy and higher dose of radiotherapy
- Alternative chemotherapy and standard dose of radiotherapy
- Alternative chemotherapy and higher dose of radiotherapy
Patients who are responding to standard chemotherapy (or where the response is unknown or those who were not eligible for PET scan portion of the study) will be allocated by a computer to one of two groups detailed below:
- Standard chemotherapy and standard dose of radiotherapy
- Standard chemotherapy and higher dose of radiotherapy
The arms within each of the groups above (responders and non-responders) will be equal in size and patients will be allocated randomly by a computer.
This study will also compare the way that this treatment affects the two different cell types found in oesophageal tumours.
The effects of the different treatment, together with the costs of the different treatment and the effects on quality of life will be analysed to see which is more effective for each of the different groups.
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
- 17 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm 1 (carboplatin/paclitaxel+standard RT dose)
Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 2: Week 4-6: carboplatin AUC 5 on D1 and paclitaxel 175mg/m2 on D1
Week 7-11: Weekly carboplatin AUC 2 and paclitaxel 50mg/m2 concomitant with radiotherapy (50Gy/25 fractions)
干预措施: Carboplatin (Drug)
Arm 1 (carboplatin/paclitaxel+standard RT dose)
Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 2: Week 4-6: carboplatin AUC 5 on D1 and paclitaxel 175mg/m2 on D1
Week 7-11: Weekly carboplatin AUC 2 and paclitaxel 50mg/m2 concomitant with radiotherapy (50Gy/25 fractions)
干预措施: Paclitaxel (Drug)
Arm 1 (carboplatin/paclitaxel+standard RT dose)
Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 2: Week 4-6: carboplatin AUC 5 on D1 and paclitaxel 175mg/m2 on D1
Week 7-11: Weekly carboplatin AUC 2 and paclitaxel 50mg/m2 concomitant with radiotherapy (50Gy/25 fractions)
干预措施: Cisplatin (Drug)
Arm 1 (carboplatin/paclitaxel+standard RT dose)
Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 2: Week 4-6: carboplatin AUC 5 on D1 and paclitaxel 175mg/m2 on D1
Week 7-11: Weekly carboplatin AUC 2 and paclitaxel 50mg/m2 concomitant with radiotherapy (50Gy/25 fractions)
干预措施: Capecitabine (Drug)
Arm 1 (carboplatin/paclitaxel+standard RT dose)
Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 2: Week 4-6: carboplatin AUC 5 on D1 and paclitaxel 175mg/m2 on D1
Week 7-11: Weekly carboplatin AUC 2 and paclitaxel 50mg/m2 concomitant with radiotherapy (50Gy/25 fractions)
干预措施: Radiotherapy (Radiation)
Arm 2 (cisplatin/capecitabine+standard RT dose)
Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 2: Week 4-6: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 3: Week 7-9: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 4: Week 10-11: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-14
Cycles 3 and 4 are given concomitantly with radiotherapy (50Gy/25 fractions). Capecitabine stops on last day of RT.
干预措施: Cisplatin (Drug)
Arm 2 (cisplatin/capecitabine+standard RT dose)
Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 2: Week 4-6: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 3: Week 7-9: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 4: Week 10-11: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-14
Cycles 3 and 4 are given concomitantly with radiotherapy (50Gy/25 fractions). Capecitabine stops on last day of RT.
干预措施: Capecitabine (Drug)
Arm 2 (cisplatin/capecitabine+standard RT dose)
Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 2: Week 4-6: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 3: Week 7-9: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 4: Week 10-11: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-14
Cycles 3 and 4 are given concomitantly with radiotherapy (50Gy/25 fractions). Capecitabine stops on last day of RT.
干预措施: Radiotherapy (Radiation)
Arm 3 (carboplatin/paclitaxel+high RT dose)
Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 2: Week 4-6: carboplatin AUC 5 on D1 and paclitaxel 175mg/m2 on D1
Week 7-11: Weekly carboplatin AUC 2 and paclitaxel 50mg/m2 concomitant with radiotherapy (60Gy/25 fractions)
干预措施: Carboplatin (Drug)
Arm 3 (carboplatin/paclitaxel+high RT dose)
Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 2: Week 4-6: carboplatin AUC 5 on D1 and paclitaxel 175mg/m2 on D1
Week 7-11: Weekly carboplatin AUC 2 and paclitaxel 50mg/m2 concomitant with radiotherapy (60Gy/25 fractions)
干预措施: Paclitaxel (Drug)
Arm 3 (carboplatin/paclitaxel+high RT dose)
Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 2: Week 4-6: carboplatin AUC 5 on D1 and paclitaxel 175mg/m2 on D1
Week 7-11: Weekly carboplatin AUC 2 and paclitaxel 50mg/m2 concomitant with radiotherapy (60Gy/25 fractions)
干预措施: Cisplatin (Drug)
Arm 3 (carboplatin/paclitaxel+high RT dose)
Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 2: Week 4-6: carboplatin AUC 5 on D1 and paclitaxel 175mg/m2 on D1
Week 7-11: Weekly carboplatin AUC 2 and paclitaxel 50mg/m2 concomitant with radiotherapy (60Gy/25 fractions)
干预措施: Capecitabine (Drug)
Arm 3 (carboplatin/paclitaxel+high RT dose)
Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 2: Week 4-6: carboplatin AUC 5 on D1 and paclitaxel 175mg/m2 on D1
Week 7-11: Weekly carboplatin AUC 2 and paclitaxel 50mg/m2 concomitant with radiotherapy (60Gy/25 fractions)
干预措施: Radiotherapy (Radiation)
Arm 4 (Cisplatin+Capecitabine+high RT dose)
Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 2: Week 4-6: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 3: Week 7-9: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 4: Week 10-11: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-14 Cycles 3 and 4 are given concomitantly with radiotherapy (60Gy/25 fractions). Capecitabine stops on last day of RT.
干预措施: Cisplatin (Drug)
Arm 4 (Cisplatin+Capecitabine+high RT dose)
Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 2: Week 4-6: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 3: Week 7-9: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 4: Week 10-11: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-14 Cycles 3 and 4 are given concomitantly with radiotherapy (60Gy/25 fractions). Capecitabine stops on last day of RT.
干预措施: Capecitabine (Drug)
Arm 4 (Cisplatin+Capecitabine+high RT dose)
Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 2: Week 4-6: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 3: Week 7-9: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21
Cycle 4: Week 10-11: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-14 Cycles 3 and 4 are given concomitantly with radiotherapy (60Gy/25 fractions). Capecitabine stops on last day of RT.
干预措施: Radiotherapy (Radiation)
结局指标
主要结局
Primary endpoint phase in adenocarcinoma phase II comparing standard dose radiotherapy to high dose radiotherapy
时间窗: 24 weeks
24 week treatment failure free survival (TFFS).
Primary endpoint phase II in squamous cell carcinoma comparing standard dose radiotherapy to high dose radiotherapy
时间窗: 24 weeks
24 week treatment failure free survival (TFFS).
Primary endpoint in adenocarcinoma when switching chemotherapy
时间窗: 24 weeks
24 week treatment failure free survival (TFFS).
Primary endpoint phase III in squamous cell carcinoma: Overall survival (OS) comparing standard dose radiotherapy to high dose radiotherapy
时间窗: 24 weeks
Overall survival (OS)
Primary endpoint in squamous cell carcinoma when switching chemotherapy
时间窗: 24 weeks
24 week treatment failure free survival (TFFS).
次要结局
- Overall survival(5 years follow up)
- Toxicity(After each treatment cycle and at follow up visits)
- Progression free survival(5 years)
- Health economics(Baseline, end of treatment, 6, 12 and 24 months)
- Quality of Life(Baseline, week 7, end of treatment, 6, 12 and 24 months)
研究者
Lisette Nixon
Senior Trial Manager
Velindre NHS Trust