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

Gastric Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02150447
• Other study ID #: NCCCTS09420
• Secondary ID: 09100901210520
• Status: Terminated
• Phase: Phase 3
• First received: May 26, 2014
• Last updated: April 2, 2018
• Start date: June 2009
• Est. completion date: May 2017

Study information

• Verified date: April 2018
• Source: National Cancer Center, Korea
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Terminated
• Enrollment: 394
• Est. completion date: May 2017
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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)

Related Conditions & MeSH terms

• Bleeding
• Gastric Cancer
• Hemorrhage
• Stomach Neoplasms

Intervention

Drug:
• Proton pump inhibitor
Lansoprazole 30 mg, daily
• Placebo
Placebo, daily

Locations

Country	Name	City	State
Korea, Republic of	Kosin University Gospel Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	National Cancer Center	Goyang
Korea, Republic of	Gyeong Sang National University Hospital	Jinju

Sponsors (4)

Lead Sponsor	Collaborator
National Cancer Center, Korea	Gyeong Sang National University Hospital, Kosin University Gospel Hospital, Pusan National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Transfusion requirement (packed RBC unit)	Unit of packed RBC required at the time of tumor bleeding	Up to 6 years of study period
Secondary	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
Secondary	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
Secondary	Overall survival		Up to 6 years of study period