Clinical trial NCT01444014: YF476 and Type I Gastric Carcinoids (Norway)
Official title: A Single Centre, Pilot Trial of YF476 in Patients With Chronic Atrophic Gastritis, Hypergastrinaemia and Type I Gastric Carcinoids
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Atrophic Gastritis
Hypergastrinemia
Type I Gastric Carcinoids
Keywords: YF476
netazepide
hypergastrinaemia
gastric carcinoids
Lead sponsor: Trio Medicines Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Norwegian University of Science and Technology
First posted: 2011-09-30
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Visual assessment of the number of gastric carcinoids.
timeFrame: 2 years
measure: Visual assessment of the size of gastric carcinoids
timeFrame: 2 years
measure: Visual assessment of the distribution of gastric carcinoids.
timeFrame: 2 years
Secondary outcomes:
measure: Safety and tolerability of YF476, as judged by medical examinations, vital signs, ECG, safety tests of blood and urine, and adverse events.
timeFrame: 2 years
measure: Histologic grading of biopsies.
timeFrame: 2 years
measure: Plasma concentrations of YF476.
timeFrame: 2 years
measure: Plasma or serum concentrations of biomarkers such as gastrin and chromogranin A (CgA)
timeFrame: 2 years
Other outcomes:
Locations:
city: Trondheim
country: Norway
facility: Institutt for kreftforskning og molekylaer medisin
Study officials:
affiliation: St Olav's Hospital/NTNU
name: Helge Waldum, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Trio Medicines Ltd.
name: Malcolm Boyce, BSc FRCP FFPM
role: STUDY_DIRECTOR
References: