Clinical trial NCT02150447: 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
Overall status: TERMINATED
Phase: PHASE3
Conditions: Gastric Cancer
Bleeding
Keywords: Gastric cancer bleeding
Proton pump inhibitor
Lead sponsor: National Cancer Center, Korea
Sponsor class: OTHER_GOV
Collaborators: name: Pusan National University Hospital
name: Kosin University Gospel Hospital
name: Gyeongsang National University Hospital
First posted: 2014-05-29
Enrollment: 394
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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)

Primary outcomes:
measure: Time-to-bleeding event
timeFrame: Up to 6 years of study period
Secondary outcomes:
measure: Transfusion requirement (packed RBC unit)
timeFrame: Up to 6 years of study period
measure: Number of endoscopy to evaluate tumor bleeding
timeFrame: Up to 6 years of study period
measure: Number of endoscopic treatment for cancer bleeding
timeFrame: Up to 6 years of study period
measure: Overall survival
timeFrame: Up to 6 years of study period
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: Kosin University Gospel Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Goyang
country: Korea, Republic of
facility: National Cancer Center
city: Jinju
country: Korea, Republic of
facility: Gyeong Sang National University Hospital
Study officials:
affiliation: National Cancer Center, Korea
name: Il Ju Choi, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Pusan National University Hospital
name: Gwang Ha Kim, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Kosin University Gospel Hospital
name: Moo In Park, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Gyeongsang National University Hospital
name: Won Sup Lee, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.