NEoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy with Salvage Surgery As Needed (NEEDS Trial)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 1,020
- 试验地点
- 12
- 主要终点
- Eating restrictions
研究概览
简要总结
NEEDS is a pragmatic open-label, randomised, controlled, phase III, multicenter trial with non-inferiority design with regard to the first co-primary endpoint overall survival and superiority for the experimental intervention definitive chemoradiotherapy. A second co-primary endpoint is global health related quality of life (HRQOL) one year after randomisation. A third co-primary endpoint is eating restictions one year after randomisation.
The aim is to compare outcomes after neoadjuvant chemoradiotherapy with subsequent esophagectomy to definitive chemoradiotherapy with surveillance and salvage esophagectomy as needed in patients with resectable locally advanced squamous cell carcinoma (SCC) of the esophagus, with the aim to provide generalisable guidance for future clinical practice.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histopathologically confirmed SCC of the esophagus in locally advanced stages cT1 N+ or cT2-4a any N, M0, according to current (8th) version of of the AJCC TNM classification.
- •Technically resectable disease according to the local multidisciplinary team conference (MDT)/tumor board.
- •Performance status ECOG 0-
- •Adequate organ function.
- •Women of childbearing potential (WOCBP*) must have a negative serum or urine pregnancy test.
- •Patients of childbearing/reproductive potential should use highly effective method of birth control measures during the study treatment period and for at least five months after the last study treatment.
- •Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment.
- •Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
- •Before patient registration/randomization, written informed consent must be given according to ICH/GCP/GDPR and national/local regulations.
排除标准
- •M1 according to current (8th) version of of the AJCC TNM classification.
- •cT4b according to current (8th) version of of the AJCC TNM classification.
- •Primary tumor not resectable without laryngectomy.
- •Impaired renal, hepatic, cardiac, pulmonary or endocrine status that compromises the eligibility of the patient for multimodality treatment with chemoradiotherapy followed by esophagectomy.
- •Subjects not considered likely to tolerate multimodality treatment with chemoradiotherapy followed by esophagectomy.
- •Subjects with previous malignancies are excluded unless a complete remission or complete resection was achieved at least 5 years prior to study entry.
- •Prior or concomitant treatment with radiotherapy or chemoradiotherapy with potential overlap of radiotherapy fields.
- •Known uncontrollable hypersensitivity to the components of the chemotherapeutic agents used in the trial regimens.
- •Inability to fully understand and digest study patient information or to comply with study instructions due to language difficulty or cognitive failure such as dementia or severe psychiatric disorder.
- •(Criteria slightly shortened)
研究组 & 干预措施
Control arm (A)
Neoadjuvant chemoradiotherapy followed by esophagectomy.
Radiotherapy: 1.8 Gy fractions 5 days per week in 23 fractions to a total dose of 41.4 Gy.
Chemotherapy: Carboplatin AUC 2 + Paclitaxel 50mg/m2 weekly x 5 (day 1, 8, 15, 22, 29), starting on the first day of radiotherapy.
Esophagectomy: Within 8 weeks of termination of chemoradiotherapy,
干预措施: Esophagectomy (Procedure)
Experimental arm (B)
Definitive chemoradiotherapy followed by surveillance, and esophagectomy only in case of residual or recurrent locoregional cancer.
Radiotherapy: Two alternative schemes:
- 1.8 Gy fractions five days per week in 28 fractions to a total dose of 50.4 Gy.
- 2.0 Gy fractions five days per week in 25 fractions to a total dose of 50 Gy.
Chemotherapy: Three alternative regimens:
- Platin-Taxane Regimen: Carboplatin AUC 2 + Paclitaxel 50mg/m2 on day 1 weekly during the full course of radiotherapy.
2a. Platinum-Fluoropyrimidine Regimen: Cisplatin 75mg/m2 weeks 1 and 5 + 5-fluorouracil 1000 mg/m2/day by continuous infusion weeks 1 and 5.
2b. FOLFOX: Oxaliplatin 85 mg/m2, calcium folinate 200 mg/m2 and 5-fluorouracil 400 mg/m2 weeks 1, 3 and 5 + 5-fluorouracil 800 mg/m2 by continuous infusion weeks 1, 3 and 5.
干预措施: Neoadjuvant radiotherapy (arm B) (Radiation)
Control arm (A)
Neoadjuvant chemoradiotherapy followed by esophagectomy.
Radiotherapy: 1.8 Gy fractions 5 days per week in 23 fractions to a total dose of 41.4 Gy.
Chemotherapy: Carboplatin AUC 2 + Paclitaxel 50mg/m2 weekly x 5 (day 1, 8, 15, 22, 29), starting on the first day of radiotherapy.
Esophagectomy: Within 8 weeks of termination of chemoradiotherapy,
干预措施: Neoadjuvant radiotherapy (arm A) (Radiation)
Control arm (A)
Neoadjuvant chemoradiotherapy followed by esophagectomy.
Radiotherapy: 1.8 Gy fractions 5 days per week in 23 fractions to a total dose of 41.4 Gy.
Chemotherapy: Carboplatin AUC 2 + Paclitaxel 50mg/m2 weekly x 5 (day 1, 8, 15, 22, 29), starting on the first day of radiotherapy.
Esophagectomy: Within 8 weeks of termination of chemoradiotherapy,
干预措施: Carboplatin, paclitaxel (Drug)
Experimental arm (B)
Definitive chemoradiotherapy followed by surveillance, and esophagectomy only in case of residual or recurrent locoregional cancer.
Radiotherapy: Two alternative schemes:
- 1.8 Gy fractions five days per week in 28 fractions to a total dose of 50.4 Gy.
- 2.0 Gy fractions five days per week in 25 fractions to a total dose of 50 Gy.
Chemotherapy: Three alternative regimens:
- Platin-Taxane Regimen: Carboplatin AUC 2 + Paclitaxel 50mg/m2 on day 1 weekly during the full course of radiotherapy.
2a. Platinum-Fluoropyrimidine Regimen: Cisplatin 75mg/m2 weeks 1 and 5 + 5-fluorouracil 1000 mg/m2/day by continuous infusion weeks 1 and 5.
2b. FOLFOX: Oxaliplatin 85 mg/m2, calcium folinate 200 mg/m2 and 5-fluorouracil 400 mg/m2 weeks 1, 3 and 5 + 5-fluorouracil 800 mg/m2 by continuous infusion weeks 1, 3 and 5.
干预措施: Carboplatin, paclitaxel (Drug)
Experimental arm (B)
Definitive chemoradiotherapy followed by surveillance, and esophagectomy only in case of residual or recurrent locoregional cancer.
Radiotherapy: Two alternative schemes:
- 1.8 Gy fractions five days per week in 28 fractions to a total dose of 50.4 Gy.
- 2.0 Gy fractions five days per week in 25 fractions to a total dose of 50 Gy.
Chemotherapy: Three alternative regimens:
- Platin-Taxane Regimen: Carboplatin AUC 2 + Paclitaxel 50mg/m2 on day 1 weekly during the full course of radiotherapy.
2a. Platinum-Fluoropyrimidine Regimen: Cisplatin 75mg/m2 weeks 1 and 5 + 5-fluorouracil 1000 mg/m2/day by continuous infusion weeks 1 and 5.
2b. FOLFOX: Oxaliplatin 85 mg/m2, calcium folinate 200 mg/m2 and 5-fluorouracil 400 mg/m2 weeks 1, 3 and 5 + 5-fluorouracil 800 mg/m2 by continuous infusion weeks 1, 3 and 5.
干预措施: Cisplatin, paclitaxel (Drug)
Experimental arm (B)
Definitive chemoradiotherapy followed by surveillance, and esophagectomy only in case of residual or recurrent locoregional cancer.
Radiotherapy: Two alternative schemes:
- 1.8 Gy fractions five days per week in 28 fractions to a total dose of 50.4 Gy.
- 2.0 Gy fractions five days per week in 25 fractions to a total dose of 50 Gy.
Chemotherapy: Three alternative regimens:
- Platin-Taxane Regimen: Carboplatin AUC 2 + Paclitaxel 50mg/m2 on day 1 weekly during the full course of radiotherapy.
2a. Platinum-Fluoropyrimidine Regimen: Cisplatin 75mg/m2 weeks 1 and 5 + 5-fluorouracil 1000 mg/m2/day by continuous infusion weeks 1 and 5.
2b. FOLFOX: Oxaliplatin 85 mg/m2, calcium folinate 200 mg/m2 and 5-fluorouracil 400 mg/m2 weeks 1, 3 and 5 + 5-fluorouracil 800 mg/m2 by continuous infusion weeks 1, 3 and 5.
干预措施: Oxaliplatin, calcium folinate, 5-fluorouracil (Drug)
Experimental arm (B)
Definitive chemoradiotherapy followed by surveillance, and esophagectomy only in case of residual or recurrent locoregional cancer.
Radiotherapy: Two alternative schemes:
- 1.8 Gy fractions five days per week in 28 fractions to a total dose of 50.4 Gy.
- 2.0 Gy fractions five days per week in 25 fractions to a total dose of 50 Gy.
Chemotherapy: Three alternative regimens:
- Platin-Taxane Regimen: Carboplatin AUC 2 + Paclitaxel 50mg/m2 on day 1 weekly during the full course of radiotherapy.
2a. Platinum-Fluoropyrimidine Regimen: Cisplatin 75mg/m2 weeks 1 and 5 + 5-fluorouracil 1000 mg/m2/day by continuous infusion weeks 1 and 5.
2b. FOLFOX: Oxaliplatin 85 mg/m2, calcium folinate 200 mg/m2 and 5-fluorouracil 400 mg/m2 weeks 1, 3 and 5 + 5-fluorouracil 800 mg/m2 by continuous infusion weeks 1, 3 and 5.
干预措施: Esophagectomy (Procedure)
结局指标
主要结局
Eating restrictions
时间窗: 1 year after randomisation
EORTC QLQ-OG25 instrument. This instrument consists of 25 items covering upper gastric symptoms or problems in four categories ranging from 1 (Not at all) to 4 (Very much).
Overall survival
时间窗: 3 years after randomisation
When 398 events have occurred
Global Health-related quality of life (HRQOL)
时间窗: 1 year after randomisation
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, version 3.0 (EORTC QLQ-C30). The two items assessing global health and overall quality of life are responded to in seven categories ranging from 1 (very poor) to 7 (excellent).
次要结局
- Health related quality of life of Cancer patients(At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation)
- Health related quality of life, general health(At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation)
- Event-free survival(5 years after randomisation)
- Histopathological response according to Mandard in operated patients(5 years after randomisation)
- Treatment-related adverse events and toxicity(Up to 5 years after randomisation)
- Nutritional outcomes - weight(Up to 5 years after randomisation)
- Health related quality of life, oesophageal specific.(At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation)
- Health economy(At baseline and 6, 12, 24, 36 and 60 months after randomisation)
- Surgical complications(After surgery in operated patients, up to 5 years after randomisation)
- Gender stratified analyses of all endpoints(Up to 5 years after randomisation)
- Loco-regional and distant relapse rates(5 years after randomisation)
- Nutritional outcomes - dysphagia(Up to 5 years after randomisation)
研究者
Magnus Nilsson
Professor
Karolinska University Hospital