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

Phase 3
Terminated
Conditions
Gastric Cancer
Bleeding
Interventions
Drug: Proton pump inhibitor
Drug: Placebo
Registration Number
NCT02150447
Lead Sponsor
National Cancer Center, Korea
Brief Summary

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

Detailed Description

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
394
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Intervention groupProton pump inhibitorProton pump inhibitor (lansoprazole) therapy for the prevention of gastric cancer bleeding
Placebo groupPlaceboPlacebo for the prevention of gastric cancer bleeding
Primary Outcome Measures
NameTimeMethod
Time-to-bleeding eventUp to 6 years of study period

Evaluation of the effect of PPI on the prevention of gastric cancer bleeding

Secondary Outcome Measures
NameTimeMethod
Overall survivalUp to 6 years of study period
Number of endoscopy to evaluate tumor bleedingUp to 6 years of study period

No of endoscopic session to evaluation bleeding from advanced gastric cancer

Transfusion requirement (packed RBC unit)Up to 6 years of study period

Unit of packed RBC required at the time of tumor bleeding

Number of endoscopic treatment for cancer bleedingUp to 6 years of study period

Total number of endoscopic treatment perfomed for gastric cancer bleeding in each patient

Trial Locations

Locations (4)

National Cancer Center

🇰🇷

Goyang, Korea, Republic of

Gyeong Sang National University Hospital

🇰🇷

Jinju, Korea, Republic of

Kosin University Gospel Hospital

🇰🇷

Busan, Korea, Republic of

Pusan National University Hospital

🇰🇷

Busan, Korea, Republic of

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