Digestive System Diseases

All Conditions

Neoplasms

Gastroesophageal Reflux

Adenocarcinoma

Barrett Esophagus

Precancerous Conditions

Esophageal Diseases

Gastrointestinal Diseases

All Drugs and Chemicals

Gastrins

Placebo pill (identical in appearance to YF476 pills)

25 mg: one capsule to be taken by mouth once daily for 12 weeks.

YF476

Matching placebo: one capsule to be taken by mouth once daily for 12 weeks.

Placebo

Julian A Abrams, MD, MS

The purpose of this study is to determine whether treatment with an experimental drug called YF476 in patients with Barrett's esophagus reduces the expression of tissue markers that are associated with an increased risk of developing esophageal cancer.

The association between gastro-esophageal reflux disease (GERD) and cancer of the esophagus is well-established. Barrett's esophagus (BE) is a condition in which the lining of the part of the esophagus changes to look like small intestine, and this change occurs in the setting of GERD. Patients with BE are at increased risk for developing esophageal cancer. It is recommended that all patients with BE take medicines called proton pump inhibitors (PPIs), which greatly reduce the acid produced by the stomach, in the hopes of reducing the risk of esophageal cancer. However, by reducing the acid level in the stomach, levels of a hormone called gastrin are increased. There is laboratory data to suggest that gastrin may have effects that actually promote the development of cancer, including esophageal cancer. The investigators previously showed that BE patients with very high gastrin levels are more likely to have either advanced precancerous changes (also called high grade dysplasia) or cancer of the esophagus. As such, the obvious question is raised: does gastrin promote the development of cancer in BE? YF476 is a new drug that blocks the effects of gastrin. Trials in healthy subjects have demonstrated that the drug is safe and well-tolerated. The investigators therefore propose to conduct a randomized placebo-controlled trial of YF476 in patients with Barrett's esophagus. The primary hypothesis is that treatment with YF476 will reduce the expression of tissue markers that are associated with an increased risk of developing esophageal cancer.

Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus

Randomized Placebo-Controlled Trial of YF476, a Gastrin Receptor Antagonist, in Barrett's Esophagus

The study is designed to examine change in tissue Ki67 expression, a marker of cellular proliferation.

Participants with changes in gene expression were assessed by RNA-sequencing (i.e., sample has sufficient RNA for analysis) between baseline and up to 3 months are tallied.

A measure of safety and tolerability. Participants with recorded adverse events were tallied. The events include any adverse events and/or severe adverse events.

Trio Medicines Ltd.

Columbia University

YF476 (gastrin-receptor antagonist)

YF476: 25 mg: one capsule to be taken by mouth once daily for 12 weeks.

Placebo pill (identical in appearance to YF476 pills)

Placebo: Matching placebo: one capsule to be taken by mouth once daily for 12 weeks.

Total

Age, Continuous

Sex: Female, Male

Race, white

Race/Ethnicity, Customized

Waist circumference

Current smoker

Proton Pump Inhibitor (PPI) frequency

Aspirin Use

Maximal Barrett's esophagus length (Prague M)

Barrett's Esophagus length

Hiatal hernia size

Serum gastrin

Plasma CgA

Relatively small sample size; study enrollment was limited to Barrett's esophagus without dysplasia, limited analysis of treatment related to later stages of disease progression; only one dose was tested which limits possibility that higher doses would have been more bioactive in Barrett's esophagus tissue.

Julian A Abrams, MD

Analysis limited to those who completed study (10 subjects in the intervention group and 10 subjects in the placebo group).

Mean Ki67 Expression

Number of Participants That Experienced Change in Any Biomarker Expression

Serious Adverse Event

Any Adverse Event

Number of Participants That Experienced Adverse Events

Overall Study

Symptoms and General Pathology

Gland and Hormone Related Diseases

Rare Diseases

Syndrome

Carcinoid Tumor

Gastrinoma

Zollinger-Ellison Syndrome

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Paraneoplastic Syndromes

Gastrointestinal Neoplasms

Digestive System Neoplasms

Peptic Ulcer

Ulcer

Duodenal Diseases

Intestinal Diseases

Stomach Diseases

Carcinoma, Islet Cell

Pancreatic Neoplasms

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Neuroendocrine Tumor

Neuroepithelioma

Pancreatic Cancer

The dose will be 100 mg YF476 once daily. When 6 patients have completed 12 weeks' treatment with that dose, it may be increased to 150 or 200 mg once daily. Patients will have type II gastric carcinoids and/or ECL cell hyperplasia/dysplasia.

This study will evaluate whether treatment with YF476 is safe and effective in reducing the size of type II gastric carcinoid tumours, or limiting the abnormal growth of gastric ECL cells, in patients with Zollinger-Ellison syndrome.

YF476 and Type II Gastric Carcinoids

A Pilot Trial of YF476, a Gastrin Antagonist, in Patients With Type II Gastric Carcinoids Associated With Zollinger-Ellison Syndrome

Regression is defined as a 25% reduction in the size / number of endoscopically evident type II gastric carcinoids. For each participant, three gastric carcinoids were identified and measured at baseline. The same gastric carcinoids were then measured at the Week 12 visit and the percentage difference in size from baseline calculated. The mean percentage change of the three gastric carcinoids per participant is recorded.

A reduction of 25% in the gastric ECL cell density.

Reduction in the histological grade of the carcinoids/hyperplasia when compared to baseline.

The level of a key biomarker chromogranin A (CgA) that is circulating in the blood was measured.

Assessed by changes in drug-controlled gastric acid analysis. A nasogastric tube (NGT) was placed through one nare and into the stomach. Gastric secretions were suctioned and discarded at T = 0 and then aspirated for 1 h in 15 min increments to measure the control acid output. Patients who could not tolerate NGT placement had endoscopic gastric analysis (EGA) performed during upper endoscopy. During EGA, a single 10 - 15 min collection was aspirated under direct visualization. Patients 01 and 02 had acid measured via NGT, whereas Patient 03 had acid measured via EGA. At the Week 2 visit, the baseline acid control was measured. At the Week 6 visit, the acid control was measured after a dose of netazepide. Results are provided for three acid control measures:

1. Volume of aspirate (mL)
2. Acid in aspirate (mEq)
3. Acid output (mEq)

Assessed by the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) instrument. Patients assessed a total of 10 symptoms on a scale of 0-5 where: 0 = no symptoms; 1 = symptoms noticeable, but not bothersome; 2 = symptoms noticeable and bothersome, but not every day; 3 = symptoms bothersome everyday; 4 = symptoms affect daily activities; and 5 = symptoms are incapacitating (unable to do daily activities). The total score was summed and reported. The maximum obtainable total score was 50 and minimum obtainable total score was 0, with higher scores indicating a worse outcome and lower scores indicating a better outcome.

Assessed by monitoring adverse events reported by patients

The level of gastrin biomarkers circulating in the blood was measured.

National Institutes of Health (NIH)

Any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with that treatment.

The dose will be an oral dose of 100 mg YF476 once daily. for 12 weeks. When 6 patients have completed 12 weeks' treatment with that dose, it may be increased to 150 or 200 mg once daily. Patients will have type II gastric carcinoids and/or ECL cell hyperplasia/dysplasia.

YF476: Gastrin receptor antagonist

Eligible Patients

The dose will be 100 mg YF476 once daily. When 6 patients have completed 12 weeks' treatment with that dose, it may be increased to 150 or 200 mg once daily. Patients will have type II gastric carcinoids and/or ECL cell hyperplasia/dysplasia.

YF476: Gastrin receptor antagonist

Age, Categorical

Race (NIH/OMB)

United States

Region of Enrollment

Patient 01

Patient 02

Patient 03

Serum chromagraninA (CgA)

Size of gastric carcinoids

Dr Malcolm Boyce

Patient 01, Week 12 visit

Patient 02, Week 12 visit

Patient 03, Week 12 visit

The mean percentage decrease in three gastric carcinoids (measured at Week 12 visit) compared with baseline.

Regression of Gastric Carcinoids and/or ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy

Patients received 100 mg YF476 orally once daily for 12 weeks.

Due to the early termination of the study, the data for this outcome measure were not collected.

A Reduction of 25% in the Gastric ECL Cell Density.

Improvement in Histological Grade of Gastric Carcinoids/ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy

Patient 01, Week 6 visit

Patient 01, Follow-up

Patient 02, Week 6 visit

Patient 02, Follow up

Patient 03, Week 6 visit

Patient 03, Follow-up

The CgA data is provided for each participant at each visit

Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples

Patient 01, Week 2 visit, Day 1, 0 - 15 min

Patient 01, Week 2 visit, Day 1, 15 - 30 min

Patient 01, Week 2 visit, Day 1, 30 - 45 min

Patient 01, Week 2 visit, Day 1, 45 - 60 min

Patient 01, Week 6 visit, Day 1, 0 - 15 min

Patient 01, Week 6 visit, Day 1, 15 - 30 min

Patient 01, Week 6 visit, Day 1, 30 - 45 min

Patient 01, Week 6 visit, Day 1, 45 - 60 min

Patient 02, Week 2 visit, Day 1, 0 - 15 min

Patient 02, Week 2 visit, Day 1, 15 - 30 min

Patient 02, Week 2 visit, Day 1, 30 - 45 min

Patient 02, Week 2 visit, Day 1, 45 - 60 min

Patient 02, Week 6 visit, Day 1, 0 - 15 min

Patient 02, Week 6 visit, Day 1, 15 - 30 min

Patient 02, Week 6 visit, Day 1, 30 - 45 min

Patient 02, Week 6 visit, Day 1, 45 - 60 min

Patient 02, Week 6 visit, Day 1, 60 - 75 min

Patient 03, Week 2 visit, Day 1, 0 - 15 min

Patient 03, Week 6 visit, Day 1, 0 - 15 min

The dose will be an oral dose of 100 mg YF476 once daily for 12 weeks. When 6 patients have completed 12 weeks' treatment with that dose, it may be increased to 150 or 200 mg once daily. Patients will have type II gastric carcinoids and/or ECL cell hyperplasia/dysplasia.

YF476: Gastrin receptor antagonist

Patients had the volume of gastric aspirate measured at Week 2 and Week 6 visit, by either nasogastric tube (NGT; Patient 01 and Patient 02) or endoscopic gastric analysis (EGA; Patient 03). Data is provided for each visit and participant.

Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate

Data was not collect due to early termination of the study.

Decrease in ECL Cell-specific Products Assessed by Quantitative PCR

Patient 1, Week 2 visit

Patient 1, Week 6 visit

Patient 1, Week 12 visit

Patient 1, Follow up visit

Patient 2, Week 2 visit

Patient 2, Week 6 visit

Patient 2, Week 12 visit

Patient 2, Follow up visit

Patient 3, Week 2 visit

Patient 3, Week 6 visit

Patient 3, Week 12 visit

Patient 3, Follow up visit

For each patient, the total score on the GERD-HRQL assessment questionnaire at each visit was summed and reported. Data is provided for each visit and participant.

Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument

Week 2 visit: number of treatment related adverse events

Week 6 visit: number of treatment related adverse events

Week 12 visit: number of treatment related adverse events

Follow up visit: number of treatment related adverse events

Safety and Tolerability

Patient 02, Follow-up

Patient 03, Week 6

Patient 03, Week 12

Data is provided for each visit of each patient. Follow up data is missing for Patient 03 (samples were taken but results not provided).

Circulating Plasma Concentration of Gastrin

Patients had the acid content in gastric aspirate measured at Week 2 and Week 6 visit, by either nasogastric tube (NGT; Patient 01 and Patient 02) or endoscopic gastric analysis (EGA; Patient 03). Data is provided for each visit and participant.

Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate

Patients had acid output measured at Week 2 and Week 6 visit, by either nasogastric tube (NGT; Patient 01 and Patient 02) or endoscopic gastric analysis (EGA; Patient 03). Data is provided for each visit and participant.

Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output

Atrophy

Gastritis, Atrophic

Gastritis

Pathological Conditions, Anatomical

Gastroenteritis

Chronic Graft Versus Host Disease

50 mg once daily for 12 weeks, with the option to increase to 75 mg or 100 mg once daily after 6 weeks, or decrease to 25 mg once daily, depending on response. After that, patients that have benefited from treatment may take 50 mg YF476 once daily for an additional up to 52 weeks.

Malcolm Boyce, BSc FRCP FFPM

Mark Pritchard, PhD FRCP

The aim of the study is to find out if the experimental medicine, YF476, can make gastric carcinoids, a rare type of stomach tumour, shrink and disappear. Gastric carcinoids occur mainly in patients with chronic atrophic gastritis (CAG), a condition in which the acid-producing cells in the lining of the stomach can't make acid. Acid production is controlled by gastrin, a hormone (chemical messenger) that's released into the bloodstream. If the stomach can't make acid, blood levels of gastrin rise. High blood levels of gastrin in patients with CAG can cause other cells (ECL cells) in the lining of the stomach to grow and, over the years, to give rise to gastric carcinoids. Gastric carcinoids are usually benign, but they can become malignant. Therefore, patients with CAG and gastric carcinoids have the inside of their stomach checked regularly, by gastroscopy, to see if the gastric carcinoids need removing surgically. A gastroscope is a thin (1 cm), flexible tube at end of which is a mini video camera, which enables the user to inspect the lining of the stomach and a 'snare' to take samples of tissue (biopsies). YF476 (netazepide) is a gastrin receptor antagonist (blocks the effects of gastrin), so it's a potential new medical treatment for gastric carcinoids in patients with CAG. Up to 10 of these patients will take YF476 daily for up to 12 weeks. If they benefit from that treatment, they may take YF476 daily for up to another 52 weeks. They'll make several outpatient visits for tests, including checks on the safety of YF476. At some of the visits, they'll have a gastroscopy. At each gastroscopy, the gastric carcinoids will be measured and biopsies taken for laboratory tests.

YF476 and Type I Gastric Carcinoids

A Single Centre, Pilot Trial of YF476 in Patients With Chronic Atrophic Gastritis, Hypergastrinaemia and Type I Gastric Carcinoids

Royal Liverpool University Hospital

Patients will take 25 mg YF476 once daily for 12 weeks

Patients will take matching placebo once daily for 12 weeks

YF476 placebo

Julian A Abrams, MD MS

A phase 2, randomised, double-blind, out-patient trial to determine if YF476 is a safe and effective treatment in patients with Barrett's esophagus.

YF476 in Barrett's Esophagus

Randomized, Placebo-controlled Trial of YF476, a Gastrin Receptor Antagonist, in Barrett's Esophagus

Esophagogastroduodenoscopy (EGD) was performed to enable taking biopsies for assessment of Ki67 expression, a marker of cellular proliferation. Ki67 expression was assessed by immunohistochemistry and calculating the number of Ki67 positive cells per mm\^2 of Barrett's epithelium.

Blood samples were taken for assay of biomarkers associated with esophageal adenocarcinoma. Changes in biomarker expression were derived from RNA-Sequencing and calculated as log-fold change comparing the treatment group to the placebo group. The nature of how results are derived by RNA-sequencing means summary statistics cannot be generated individually for each arm and a value has not been calculated for each individual participant. Therefore, results are reported as the relative change in biomarker expression in the treatment arm compared to the placebo arm.

Blood samples were taken to assess the effects of YF476 on fasting serum gastrin, a marker of gastric acid suppression

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus	NCT01298999	Barrett's Esoph...	YF476 Placebo	18 Years -	Columbia University
YF476 and Type II Gastric Carcinoids	NCT02454075	Zollinger-Ellis...	YF476	18 Years -	Trio Medicines Ltd.
Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus	NCT01298999	Barrett's Esoph...	YF476 Placebo	18 Years -	Columbia University
YF476 and Type I Gastric Carcinoids	NCT01339169	Chronic Atrophi... Hypergastrinaem... Type I Gastric ...	YF476	18 Years -	Trio Medicines Ltd.
YF476 in Barrett's Esophagus	NCT02597712	Barrett's Esoph...	YF476 YF476 placebo	18 Years -	Trio Medicines Ltd.

Spots Global Cancer Trial Database for yf476

Every month we try and update this database with for yf476 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for yf476

Every month we try and update this database with for yf476 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for yf476 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.