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

Primary Purpose

Gastric Cancer, Bleeding

Status

Terminated

Phase

Phase 3

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Proton pump inhibitor

Placebo

About this trial

This is an interventional prevention trial for Gastric Cancer focused on measuring Gastric cancer bleeding, Proton pump inhibitor

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

Kosin University Gospel Hospital
Pusan National University Hospital
National Cancer Center
Gyeong Sang National University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Intervention group

Placebo group

Arm Description

Proton pump inhibitor (lansoprazole) therapy for the prevention of gastric cancer bleeding

Placebo for the prevention of gastric cancer bleeding

Outcomes

Primary Outcome Measures

Time-to-bleeding event

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

Secondary Outcome Measures

Transfusion requirement (packed RBC unit)

Unit of packed RBC required at the time of tumor bleeding

Number of endoscopy to evaluate tumor bleeding

No of endoscopic session to evaluation bleeding from advanced gastric cancer

Number of endoscopic treatment for cancer bleeding

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

Overall survival

Full Information

NCT ID

NCT02150447

First Posted

May 26, 2014

Last Updated

April 2, 2018

Sponsor

National Cancer Center, Korea

Collaborators

Pusan National University Hospital, Kosin University Gospel Hospital, Gyeongsang National University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02150447

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2018

Overall Recruitment Status

Terminated

Why Stopped

Low enroll rate

Study Start Date

June 2009 (undefined)

Primary Completion Date

April 2015 (Actual)

Study Completion Date

May 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

National Cancer Center, Korea

Collaborators

Pusan National University Hospital, Kosin University Gospel Hospital, Gyeongsang National University Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gastric Cancer, Bleeding

Keywords

Gastric cancer bleeding, Proton pump inhibitor

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

394 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Intervention group

Arm Type

Active Comparator

Arm Description

Proton pump inhibitor (lansoprazole) therapy for the prevention of gastric cancer bleeding

Arm Title

Placebo group

Arm Type

Placebo Comparator

Arm Description

Placebo for the prevention of gastric cancer bleeding

Intervention Type

Drug

Intervention Name(s)

Proton pump inhibitor

Other Intervention Name(s)

Lansoprazole

Intervention Description

Lansoprazole 30 mg, daily

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo, daily

Primary Outcome Measure Information:

Title

Time-to-bleeding event

Description

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

Time Frame

Up to 6 years of study period

Secondary Outcome Measure Information:

Title

Transfusion requirement (packed RBC unit)

Description

Unit of packed RBC required at the time of tumor bleeding

Time Frame

Up to 6 years of study period

Title

Number of endoscopy to evaluate tumor bleeding

Description

No of endoscopic session to evaluation bleeding from advanced gastric cancer

Time Frame

Up to 6 years of study period

Title

Number of endoscopic treatment for cancer bleeding

Description

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

Time Frame

Up to 6 years of study period

Title

Overall survival

Time Frame

Up to 6 years of study period

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Il Ju Choi, M.D., Ph.D.

Organizational Affiliation

National Cancer Center, Korea

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Gwang Ha Kim, M.D., Ph.D.

Organizational Affiliation

Pusan National University Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Moo In Park, M.D., Ph.D.

Organizational Affiliation

Kosin University Gospel Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Won Sup Lee, M.D., Ph.D.

Organizational Affiliation

Gyeongsang National University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Kosin University Gospel Hospital

City

Busan

ZIP/Postal Code

602-702

Country

Korea, Republic of

Facility Name

Pusan National University Hospital

City

Busan

ZIP/Postal Code

620-739

Country

Korea, Republic of

Facility Name

National Cancer Center

City

Goyang

ZIP/Postal Code

410-769

Country

Korea, Republic of

Facility Name

Gyeong Sang National University Hospital

City

Jinju

ZIP/Postal Code

660-702

Country

Korea, Republic of

12. IPD Sharing Statement

Citations:

PubMed Identifier

28680717

Citation

Kim YI, Kim MJ, Park SR, Kim HK, Cho SJ, Lee JY, Kim CG, Kim GH, Park MI, Nam BH, Park YI, Choi IJ. Effect of a Proton Pump Inhibitor on Tumor Bleeding Prevention in Unresectable Gastric Cancer Patients: a Double-Blind, Randomized, Placebo-Controlled Trial. J Gastric Cancer. 2017 Jun;17(2):120-131. doi: 10.5230/jgc.2017.17.e15. Epub 2017 May 31.

Results Reference

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

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