A Randomised Phase II/III Trial of Preoperative Chemoradiotherapy Versus Preoperative Chemotherapy for Resectable Gastric Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 574
- 试验地点
- 59
- 主要终点
- Overall survival
研究概览
简要总结
Gastric cancer remains a significant global public health problem. Although in developed countries its incidence has dramatically decreased, on a worldwide scale it is still a leading cause of cancer-related deaths. Surgery is the only potentially curative treatment for gastric cancer. Although the survival rates for patients with early stage disease (stage 1A and 1B) are good, this subgroup of patients constitutes only 20% of those undergoing resection. The majority of patients will have locally advanced or metastatic disease at presentation, which has an extremely poor prognosis. The current five-year survival rate for gastric cancer in Western countries is approximately 20-30%, a figure that has improved little over the past 30 years. The intervention arm in TOPGEAR consists of pre-operative chemotherapy, pre-operative chemoradiotherapy, surgery and post-operative chemotherapy. The control arm consists of pre-operative chemotherapy, surgery and post-operative chemotherapy. The primary objective of TOPGEAR is to investigate whether the addition of chemoradiotherapy to chemotherapy is superior to chemotherapy alone in the neoadjuvant setting by improving pathological complete response rates in the first instance, and subsequently overall survival, in patients undergoing adequate surgery (D1+ dissection) for resectable gastric cancer.
详细描述
Purpose:
The purpose of this phase II/III clinical trial is to determine if pre-operative chemoradiotherapy improves overall survival in participants with resectable gastric cancer.
Trial details:
Participants will be randomised to receive either pre-operative chemotherapy or pre-operative chemoradiotherapy. The will undergo surgery and then receive further post-operative chemotherapy. Participants will be followed up for 5 years after treatment.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven adenocarcinoma of the stomach or gastroesophageal junction (GEJ) that is:
- •Stage IB (T1N1 only, T2N0 not eligible) - IIIC, i.e. T3 - T4 and/or node positive, according to American Joint Committee on Cancer (AJCC) 7th edition.
- •Considered operable following initial staging investigations (surgeon believes that an R0 resection can be achieved) (GEJ tumours are defined as tumours that arise in the cardia or at the GEJ that do not involve more than 2cm of the lower esophagus, i.e. Siewert Type II and Siewert Type III)
- •Age >=18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Adequate organ function defined as follows:
- •Bone marrow: Haemoglobin >=90 g/L, Absolute neutrophil count (ANC) >=1.5 x 10⁹ /L, White blood cell count >=3 x 10⁹ /L, Platelet count >=100 x 10⁹ /L
- •Hepatic: Serum bilirubin <=1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST) and/or alanine transaminase (ALT) <=3.0 x ULN
- •Renal: Serum creatinine <=0.150 mmol/L, Calculated creatinine clearance >=50 mL/min
- •Disease which can be radically treated with radiotherapy to 45 Gy with standard fractionation
- •Any patient with a history of ischaemic heart disease and abnormal ECG, or who is over 60 years of age should have a pre-treatment evaluation of cardiac function with a multigated acquisition (MUGA) scan or echocardiogram. Patients will only be included if the left ventricular ejection fraction is >=50%.
- •Written informed consent obtained before randomization
- •Negative pregnancy test for women of childbearing potential within 7 days of commencing study treatment. Males and females of reproductive potential must agree to practice adequate contraceptive measures.
排除标准
- •Evidence of metastatic disease
- •Prior chemotherapy or radiotherapy
- •Patients with a past history of cancer in the 5 years before randomization except for the following. Patients with squamous or basal cell carcinoma of the skin that has been effectively treated, and patients with carcinoma in situ of the cervix that has been treated by operation only are eligible, even if they were diagnosed and treated within the 5 years before randomization.
- •Patients with other significant underlying medical conditions that may be aggravated by the study treatment or are not controlled
- •Pregnant or lactating females or female patients of childbearing potential who have not been surgically sterilized or are without adequate contraceptive measures
- •Cardiac failure and other contraindications to epirubicin
- •Patients with impaired gastrointestinal absorption for whatever reason
- •Patients medically unfit for cisplatin chemotherapy due to one or more of the following reasons:
- •Clinically significant sensorineural hearing impairment (audiometric abnormalities without corresponding clinical deafness will not be regarded as a contraindication to cisplatin)
- •Severe tinnitus
- •Renal impairment (GFR <=50ml/min)
- •Peripheral neuropathy >=grade 2
- •Inability to tolerate intravenous hydration e.g due to cardiac disease
- •Co-morbidities (based on clinical judgement by the investigator) that in the view of the investigator would preclude the safe administration of cisplatin.
研究组 & 干预措施
Preoperative chemoradiotherapy
2 cycles preoperative chemotherapy with: epirubicin + cisplatin + 5-fluorouracil. (5-fluorouracil may be replaced with capecitabine).
OR epirubicin + oxaliplatin + capecitabine OR 3 cycles of 5-fluorouracil +Leucovorin + oxaliplatin + docetaxel
5 weeks preoperative chemoradiotherapy.
Gastric resection.
3 cycles adjuvant chemotherapy with: epirubicin + cisplatin + 5-fluorouracil. (5-fluorouracil may be replaced with capecitabine).
OR epirubicin + oxaliplatin + capecitabine OR 4 cycles of 5-fluorouracil +Leucovorin + oxaliplatin + docetaxel
干预措施: Epirubicin + cisplatin + 5-fluorouracil OR epirubicin + cisplatin + capecitabine OR epirubicin + oxaliplatin + capecitabine OR 5-Fluorouracil + leucovorin + oxaliplatin + docetaxel (Drug)
Preoperative chemoradiotherapy
2 cycles preoperative chemotherapy with: epirubicin + cisplatin + 5-fluorouracil. (5-fluorouracil may be replaced with capecitabine).
OR epirubicin + oxaliplatin + capecitabine OR 3 cycles of 5-fluorouracil +Leucovorin + oxaliplatin + docetaxel
5 weeks preoperative chemoradiotherapy.
Gastric resection.
3 cycles adjuvant chemotherapy with: epirubicin + cisplatin + 5-fluorouracil. (5-fluorouracil may be replaced with capecitabine).
OR epirubicin + oxaliplatin + capecitabine OR 4 cycles of 5-fluorouracil +Leucovorin + oxaliplatin + docetaxel
干预措施: Preoperative chemoradiotherapy (Radiation)
Preoperative chemoradiotherapy
2 cycles preoperative chemotherapy with: epirubicin + cisplatin + 5-fluorouracil. (5-fluorouracil may be replaced with capecitabine).
OR epirubicin + oxaliplatin + capecitabine OR 3 cycles of 5-fluorouracil +Leucovorin + oxaliplatin + docetaxel
5 weeks preoperative chemoradiotherapy.
Gastric resection.
3 cycles adjuvant chemotherapy with: epirubicin + cisplatin + 5-fluorouracil. (5-fluorouracil may be replaced with capecitabine).
OR epirubicin + oxaliplatin + capecitabine OR 4 cycles of 5-fluorouracil +Leucovorin + oxaliplatin + docetaxel
干预措施: Gastric resection (Procedure)
Preoperative chemotherapy
3 cycles preoperative chemotherapy with: epirubicin + cisplatin + 5-fluorouracil. (5-fluorouracil may be replaced with capecitabine).
OR epirubicin + oxaliplatin + capecitabine OR 4 cycles of 5-fluorouracil +Leucovorin + oxaliplatin + docetaxel
Gastric resection.
3 cycles adjuvant chemotherapy with: epirubicin + cisplatin + 5-fluorouracil. (5-fluorouracil may be replaced with capecitabine) OR epirubicin + oxaliplatin + capecitabine OR 4 cycles of 5-fluorouracil +Leucovorin + oxaliplatin + docetaxel
干预措施: Epirubicin + cisplatin + 5-fluorouracil OR epirubicin + cisplatin + capecitabine OR epirubicin + oxaliplatin + capecitabine OR 5-Fluorouracil + leucovorin + oxaliplatin + docetaxel (Drug)
Preoperative chemotherapy
3 cycles preoperative chemotherapy with: epirubicin + cisplatin + 5-fluorouracil. (5-fluorouracil may be replaced with capecitabine).
OR epirubicin + oxaliplatin + capecitabine OR 4 cycles of 5-fluorouracil +Leucovorin + oxaliplatin + docetaxel
Gastric resection.
3 cycles adjuvant chemotherapy with: epirubicin + cisplatin + 5-fluorouracil. (5-fluorouracil may be replaced with capecitabine) OR epirubicin + oxaliplatin + capecitabine OR 4 cycles of 5-fluorouracil +Leucovorin + oxaliplatin + docetaxel
干预措施: Gastric resection (Procedure)
结局指标
主要结局
Overall survival
时间窗: Up to 5 years
The interval from the date of randomisation to the date of death from any cause, or the date last known alive.
次要结局
- Surgical complete resection rate (R0)(At the time of surgery)
- Disease free survival(Up to 5 years)
- Pathological response rate(At time of surgery)
- Proportion of participants with given grades of toxicities(Up to 5 years)