Clinical trial NCT02454075: YF476 and Type II Gastric Carcinoids
Official title: A Pilot Trial of YF476, a Gastrin Antagonist, in Patients With Type II Gastric Carcinoids Associated With Zollinger-Ellison Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Zollinger-Ellison Syndrome
Keywords: YF476
netazepide
gastric carcinoids
Zollinger-Ellison syndrome
Lead sponsor: Trio Medicines Ltd.
Sponsor class: INDUSTRY
Collaborators: name: National Institutes of Health (NIH)
First posted: 2015-05-27
Enrollment: 3
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: 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.


Eligibility criteria: Inclusion criteria:

1. Men; post-menopausal women; pre-menopausal women who have been sterilised by tubal ligation, hysterectomy or bilateral oophorectomy; or pre-menopausal women using one of the allowed methods of contraception: condom and spermicide or intra-uterine device.
2. Patients with serum gastrin \>250 pg/mL.
3. Hepatic function: AST and ALT ≤2.0 x ULN; total bilirubin ≤1.0 x ULN.
4. Renal function: serum creatinine \<1.0 x ULN.
5. Haematologic function: Hb ≥10.0 g/dL; WBC ≥3.5 x 10e9 /L; ANC ≥1.5 x 10e9 /L; platelets ≥100 x 10e9 /L.
6. Coagulation parameters: INR or PT ≤1.0 x ULN; PTT ≤1.0 x ULN.
7. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial.
8. Willingness to give fully-informed, written consent.

Exclusion criteria:

1. Patients under 18 years.
2. Women who are pregnant, lactating or using a steroid contraceptive.
3. Prior gastric resection or bypass.
4. Planned gastrinoma resection during the study period.
5. Patients on somatostatin analogues, except for those on therapy for \>6 months with stable or worsening carcinoids.
6. Inability to tolerate endoscopy, or refusal of endoscopy.
7. Physical findings, ECG (especially prolonged QTc interval \>450 msec), or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the subject.
8. Certain medicines and herbal remedies taken during the 7 days before visit 2.
9. Participation in a trial of an IMP within the previous 28 days.
10. Presence of drug or alcohol abuse.
11. History or baseline findings of:

    * type 1 diabetes mellitus;
    * pancreatitis (baseline amylase and/or \>2.0 x ULN);
    * hepatitis B, hepatitis C or HIV;
    * malabsorption syndrome or inability to swallow or retain oral medicine;
    * major surgery \<28 days prior to enrolment;
    * ECOG performance status \>2; or
    * another cancer within 3 years except for basal carcinoma of the skin or cervical carcinoma in-situ.
    * Also, any clinically significant and uncontrolled major morbidity including but not limited to; serious cardiac disease (unstable angina, s/p myocardial infarction \<1 month); respiratory disease (advanced COPD or pulmonary fibrosis); uncontrolled hypertension; or active systemic infection.

Primary outcomes:
measure: Regression of Gastric Carcinoids and/or ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy
timeFrame: Week 12 visit
measure: A Reduction of 25% in the Gastric ECL Cell Density.
timeFrame: Week 12 visit
Secondary outcomes:
measure: Improvement in Histological Grade of Gastric Carcinoids/ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy
timeFrame: Week 12 visit
measure: Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples
timeFrame: Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
measure: Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate
timeFrame: Week 2 visit (baseline) and Week 6 visit
measure: Decrease in ECL Cell-specific Products Assessed by Quantitative PCR
timeFrame: Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
measure: Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument
timeFrame: Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
measure: Safety and Tolerability
timeFrame: Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
measure: Circulating Plasma Concentration of Gastrin
timeFrame: Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
measure: Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate
timeFrame: Week 2 visit (baseline) and Week 6 visit
measure: Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output
timeFrame: Week 2 visit (baseline) and Week 6 visit
Other outcomes:
Locations:
Study officials:
References: