PreOperative Treatment With chEmotheRapy or chemoRAdiatioN in esophaGeal or gastroEsophageal adenocaRcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 29
- 试验地点
- 3
- 主要终点
- treatment response
研究概览
简要总结
The best treatment for resectable esophageal or gastroesophageal adenocarcinoma is unknown. Although an operation to remove the esophagus is the most common treatment, previous studies have shown that patients live longer when either perioperative (before and after surgery) chemotherapy or preoperative (before surgery) chemotherapy plus radiation is given, compared to surgery alone. However it is unknown which of these treatments (perioperative chemotherapy or preoperative chemoradiation) is more effective in improving survival. A study where patients with resectable esophageal / GE junction cancer are chosen at random to receive one of the two preoperative treatments would help determine if one form of treatment improves survival compared to the other.
Patients with localized esophageal / GE junction cancer (adenocarcinoma) will be randomized to receive either preoperative and postoperative chemotherapy or preoperative chemoradiation followed by surgery.
The main objective of this pilot trial is to determine the possibility of conducting a larger study with many centers participating. If this study proves to be feasible with enough patients enrolled and able to tolerate treatments without major side effects then we can hopefully proceed to perform a larger multi-center trial to look for survival outcome differences between patients who receive preoperative chemotherapy and those who receive preoperative chemoradiation. The results of this trial would ultimately help us choose the most effective treatment of resectable esophageal cancer and hopefully improve survival.
详细描述
OBJECTIVE To determine the feasibility of a randomized trial of neoadjuvant chemotherapy vs. neoadjuvant chemoradiation for patients with resectable adenocarcinoma of the esophagus or gastroesophageal junction.
RESEARCH PLAN Phase III randomized 2-arm parallel group pilot study
1:1 randomization to A) or B)
TREATMENT REGIMEN A) PERIOPERATIVE CHEMOTHERAPY (OPTION of CHEMO REGIMEN 1 or 2) 1) FLOT - Four x 14 day cycles FLOT preoperatively and 4 cycles postoperatively: 5-Fluorouracil 2600 mg/m², day 1 IV every 14 days Leucovorin 200 mg/m², day 1, IV., every 14 days Oxaliplatin 85 mg/m², day 1, IV, every 14 days Docetaxel 50mg/m2, day 1, IV, every 14 days
OR
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •adenocarcinoma of esophagus or gastroesophageal junction; -cT1N1-3 or T2-4Nx; M0 by American Joint Committee on Cancer (AJCC) 7th Edition staging classification
- •proximal portion of the tumor at least 20 cm from the incisors on endoscopy, and extend no greater than 2 cm into the gastric cardia
- •tumor length < 8cm; diameter < 5 cm
- •age > 18 years
- •absolute neutrophil count (ANC) ≥ 1.5 x 109 / L
- •platelet count > 100 x 109 / L
- •creatinine clearance > 50 ml / min
- •bilirubin < 1.5x upper limit normal
- •FEV1 > 1.0 L
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Exclusion Criteria
- •positive serum / urine pregnancy test for females of childbearing age
- •previous primary / recurrent malignancy in last 5 years (history of previous / current non-melanoma skin cancer or cervical in-situ carcinoma in last 5 years acceptable for inclusion in trial)
- •previous chemotherapy for esophageal cancer
- •previous radiation therapy that would overlap required radiation fields
- •major systemic illness(es) that would limit life expectancy <2 years
- •psychiatric / cognitive illness that would limit ability to give informed consent
- •(Patients will be reviewed by both a medical and radiation oncologist and deemed fit to undergo either neoadjuvant chemotherapy or chemoradiation, respectively)
排除标准
- 未提供
研究组 & 干预措施
Neoadjuvant Chemotherapy
NEOADJUVANT CHEMOTHERAPY (OPTION of CHEMO REGIMEN 1 or 2)
-
FLOT - Four x 14 day cycles FLOT preoperatively and 4 cycles postoperatively (within 4-10 weeks after surgery): 5-Fluorouracil 2600 mg/m², day 1 IV every 14 days Leucovorin 200 mg/m², day 1, IV., every 14 days Oxaliplatin 85 mg/m², day 1, IV, every 14 days Docetaxel 50mg/m2, day 1, IV, every 14 days
-
ECF / ECX - Three x 21-day cycles ECF preoperatively and 3 cycles postoperatively (within 4-10 weeks after surgery): Epirubicin (50 mg/m²,mg per square meter of body-surface area) by intravenous bolus on day 1 IV Cisplatin: 60 mg/m², mg per square meter intravenously with hydration on day 1 IV 5-Fluorouracil: 200 mg/m², mg per square meter daily for 21 days by continuous intravenous infusionIV infusion 5-FU may be substituted with Capecitabine (Xeloda) 625mg/m2 PO BID (ECX)
干预措施: (Epirubicin Cisplatin 5-Fluorouracil / Xeloda) OR 5-Fluorouracil Leucovorin Oxaliplatin Docetaxel (Drug)
Neoadjuvant Chemoradiation
- -carboplatin and paclitaxel given on days 1, 8, 15, 22 and 29
- paclitaxel: 50 mg / m2 IV over 1 hour
- carboplatin: dosed to an area under the curve of 2, by Calvert formula, as a 1 hour IV infusion Radiation Therapy Concurrent radiation therapy will begin within 24 hours of initiation of chemotherapy for patients randomized to chemoradiation treatment.
-
Dose specifications:
-
Phase 1: Total radiation prescription dose 45 Gy given in 25 fractions of 1.8 Gy per fraction, 5 fractions / week, one treatment / day, starting on the first day of first cycle of chemotherapy.
-
Phase 2: (GTV only) Boost is not mandatory and up to the discretion of radiation oncologist. Total radiation prescription dose 5.4 Gy given in 3 fractions of 1.8 Gy per fraction, 5 fractions / week, one treatment.
干预措施: Carboplatin paclitaxel plus concurrent radiotherapy (Other)
结局指标
主要结局
treatment response
时间窗: 5 weeks for chemoradiation arm, 6-8 weeks for chemotherapy arm
\>30% of patients in both treatment arms demonstrate partial or complete response as defined by Mandard TRG 1-3 on pathologic staging
compliance with assigned neoadjuvant treatment
时间窗: 5 weeks for chemoradiation arm, 6-8 weeks for chemotherapy arm
- \>60% patients allocated for randomization will start and complete treatment without major protocol violation
次要结局
- survival(3 years)
- EORTC QOL(baseline, 3, 6, 9, 12 months post treatment)
研究者
Dr. Gordon Buduhan
MD MSc FRCSC Associate Professor of Surgery Section of Thoracic Surgery,
CancerCare Manitoba