Effect of Proton Pump Inhibitor on Prevention of Tumor Bleeding in Patients Under Palliative Chemotherapy for Unresectable Gastric Cancer: a Randomized, Double Blind, and Placebo Controlled Multicenter Trial
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 394
- 试验地点
- 4
- 主要终点
- Time-to-bleeding event
研究概览
简要总结
The aim of this study is the effect of proton pump inhibitor (PPI) with respect to gastric cancer bleeding in inoperable patients.
详细描述
Tumor bleeding frequently occurs in inoperable gastric cancer patients. Inoperable gastric cancer usually has a large ulcer with friable tumor vessels. Acidic environment in stomach prevents adequate function of coagulation cascade and decrease clot stability. Gastric cancer bleeding may cause significant morbidity and often delays scheduled chemotherapy. National Center Center data showed that about 30% of gastric cancer patient undergoing palliative chemotherapy eventually experience significant cancer bleeding during the treatment period. Once bleeding occurs, endoscopic management is more difficult in gastric cancer patients than in patients with benign peptic ulcers, because the malignant ulcer bed has significant fibrosis. Consequently, gastric cancer patient has a high risk of rebleeding.
Proton pump inhibitor (PPI, lansoprazole for example) decrease gastric acid secretion by inhibiting H+,K+-ATPase, and subsequently stabilize blood clot. PPIs are commonly used for benign peptic ulcer or reflux esophagitis, and PPI can decrease recurrent benign ulcer bleeding or other ulcer complications. Moreover, it was reported to prevent bleeding from NSAID or aspirin induced gastric ulcer. Because PPIs are very safe, and they are even available as over-the-counter drugs in some countries. Furthermore, the drug has no interaction with major chemotherapeutic agents commonly used for gastric cancer. Moreover, the drugs are prescribed to the gastric cancer patients when tumor bleeding occurs. Although gastric cancer bleeding is not uncommon and clinically challenging problem, there has been no recommended measure to prevent cancer bleeding. Also there has been no report about the efficacy of PPIs on the gastric cancer bleeding prevention up to now.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven primary gastric adenocarcinoma
- •Age ≥18 years
- •Plan for 1st line or 2nd line palliative chemotherapy
- •Cancer staging: metastatic (TxNxM1) or locally advanced unresectable gastric cancer (T4NxMx with unresectable), or T2-3NxMx with inoperable condition
- •Performance status (PS) of 0 to 2 on Eastern Cooperative Oncology Group (ECOG) scale
- •Adequate organ functions defined as indicated below: (a) WBC > 3000/mm3, (b) Hb 9.0 g/dL regardless of any transfusion history, (c) Platelet ≥100,000/mm3, (d) AST/ALT ≤ 2.5 x UNL (≤ 5 x UNL if liver metastases are present) (e) Total bilirubin ≤1.5x UNL (f) Cr ≤1.5 x UNL
- •Written informed consent
排除标准
- •Other malignancy within the past 3 years except adequately treated non-melanomatous skin cancer or carcinoma in situ of the cervix
- •Patients with significant or uncontrolled gastrointestinal bleeding in the past two weeks without evidence of resolution documented by endoscopy or colonoscopy
- •Previous subtotal gastrectomy or total gastrectomy
- •Patient with a plan for neo-adjuvant chemotherapy
- •Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome, or inability to take oral medication
- •Allergy history to proton pump inhibitor
- •Serious concurrent infection or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy
- •Inadequate cardiovascular function: (a) New York Heart Association class III or IV heart disease, (b) Unstable angina or myocardial infarction within the past 6 months, (c) History of significant ventricular arrhythmia requiring medication with antiarrhythmics or significant conduction system abnormality
- •Requirement for therapeutic anticoagulant therapy, aspirin or non-steroidal anti-inflammatory agents except COX-2 selective inhibitor
- •Requirement for therapeutic corticosteroid; the use of dexamethasone as anti-emetics or a premedication of chemotherapy-associated hypersensitivity is not an exclusion criteria
- •Need for PPI maintenance treatment for uncontrolled reflux esophagitis or active peptic ulcer
- •Psychiatric disorder that would preclude compliance
- •Pregnant or breast-feeding women
- •Untreated folate or vitamine B12 deficiency anemia
- •Bone marrow metastasis, or evidence of microangiopathic hemolytic anemia (MAHA)
研究组 & 干预措施
Intervention group
Proton pump inhibitor (lansoprazole) therapy for the prevention of gastric cancer bleeding
干预措施: Proton pump inhibitor (Drug)
Placebo group
Placebo for the prevention of gastric cancer bleeding
干预措施: Placebo (Drug)
结局指标
主要结局
Time-to-bleeding event
时间窗: Up to 6 years of study period
Evaluation of the effect of PPI on the prevention of gastric cancer bleeding
次要结局
- Overall survival(Up to 6 years of study period)
- Transfusion requirement (packed RBC unit)(Up to 6 years of study period)
- Number of endoscopy to evaluate tumor bleeding(Up to 6 years of study period)
- Number of endoscopic treatment for cancer bleeding(Up to 6 years of study period)
研究者
Il Ju Choi
Head of Gastric Cancer Cencer
National Cancer Center, Korea