YF476 and Type I Gastric Carcinoids (Norway)

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

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. They'll make up to seven outpatient visits for tests, including checks on the safety of YF476 and up to four gastroscopies. At each gastroscopy, the gastric carcinoids will be measured and biopsies taken for laboratory tests. Patients will take up to 24 weeks to finish the study.

Study Overview

• Status: Terminated
• Conditions: Chronic Atrophic Gastritis; Hypergastrinemia; Type I Gastric Carcinoids
• Intervention / Treatment: Drug: YF476

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• Norway
  • Trondheim, Norway
    • Institutt for kreftforskning og molekylaer medisin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients known to have gastric carcinoids associated with chronic atrophic gastritis and hypergastrinaemia, and who attend the outpatient clinic of the investigator;
• Men, postmenopausal women, premenopausal women who have been sterilised by tubal ligation, hysterectomy or bilateral oophorectomy, or premenopausal women using reliable contraception: condom and spermicide or intrauterine device;
• Adults ≥ 18 years;
• Good general health; and
• Able to give fully-informed, written consent.

Exclusion Criteria:

• Women who are pregnant, lactating or using a steroid contraceptive;
• History of gastric surgery, apart from surgery for gastric carcinoids;
• Evidence of Zollinger-Ellison syndrome;
• Prolonged QTc interval (>450 msec);
• Certain medicines and herbal remedies taken during the 7 days before visit 1;
• Previous treatment with somatostatin; or
• Participation in other clinical trials of unlicensed medicines within the previous 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: YF476	Drug: YF476; 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.; Other Names: netazepide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Visual assessment of the number of gastric carcinoids.	2 years
Visual assessment of the size of gastric carcinoids	2 years
Visual assessment of the distribution of gastric carcinoids.	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of YF476, as judged by medical examinations, vital signs, ECG, safety tests of blood and urine, and adverse events.	2 years
Histologic grading of biopsies.	2 years
Plasma concentrations of YF476.	2 years
Plasma or serum concentrations of biomarkers such as gastrin and chromogranin A (CgA)	2 years

Collaborators and Investigators

• Sponsor: Trio Medicines Ltd.
• Collaborators: Norwegian University of Science and Technology
• Investigators: Principal Investigator: Helge Waldum, MD PhD, St Olav's Hospital/NTNU

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (ACTUAL): May 1, 2012
• Study Completion (ACTUAL): May 1, 2012

Study Registration Dates

• First Submitted: September 28, 2011
• First Submitted That Met QC Criteria: September 28, 2011
• First Posted (ESTIMATE): September 30, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): May 15, 2015
• Last Update Submitted That Met QC Criteria: May 14, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: YF476; netazepide; hypergastrinaemia; gastric carcinoids
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Pathological Conditions, Anatomical; Neuroendocrine Tumors; Gastritis; Atrophy; Carcinoid Tumor; Gastritis, Atrophic
• Other Study ID Numbers: T-015; 2010-023151-28 (EUDRACT_NUMBER)