The Use of Proton Pump Inhibitor on the Prevention of Gastric Cancer Bleeding

Study Overview
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Brief Summary
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The aim of this study is the effect of proton pump inhibitor (PPI) with respect to gastric cancer bleeding in inoperable patients.

Detailed Description
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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.

Official Title
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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

Conditions
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Gastric Cancer, Bleeding

Intervention / Treatment
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* Drug: Proton pump inhibitor
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention group<br>Proton pump inhibitor (lansoprazole) therapy for the prevention of gastric cancer bleeding | Drug: Proton pump inhibitor<br>* Lansoprazole 30 mg, daily<br>* Other names: Lansoprazole;|
| Placebo Comparator: Placebo group<br>Placebo for the prevention of gastric cancer bleeding | Drug: Placebo<br>* Placebo, daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-to-bleeding event | Evaluation of the effect of PPI on the prevention of gastric cancer bleeding | Up to 6 years of study period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transfusion requirement (packed RBC unit) | Unit of packed RBC required at the time of tumor bleeding | Up to 6 years of study period | 
| Number of endoscopy to evaluate tumor bleeding | No of endoscopic session to evaluation bleeding from advanced gastric cancer | Up to 6 years of study period | 
| Number of endoscopic treatment for cancer bleeding | Total number of endoscopic treatment perfomed for gastric cancer bleeding in each patient | Up to 6 years of study period | 
| Overall survival |  | Up to 6 years of study period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric cancer bleeding, Proton pump inhibitor