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

National Cancer Center (NCC)

Status and phase

Terminated

Phase 3

Conditions

Gastric Cancer

Bleeding

Treatments

Drug: Placebo

Drug: Proton pump inhibitor

Study type

Interventional

Funder types

Other

Identifiers

NCT02150447

0910090 (Other Grant/Funding Number)

NCCCTS09420

1210520 (Other Grant/Funding Number)

Details and patient eligibility

About

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

Full 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.

Enrollment

394 estimated patients

Sex

All

Ages

18 to 90 years old

Volunteers

No Healthy Volunteers

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)