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

Sponsors

Lead Sponsor: Trio Medicines Ltd.

Collaborator: National Institutes of Health (NIH)

Source Trio Medicines Ltd.
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.

Overall Status Terminated
Start Date 2011-04-11
Completion Date 2012-06-22
Primary Completion Date 2012-06-22
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Regression of Gastric Carcinoids and/or ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy Week 12 visit
A Reduction of 25% in the Gastric ECL Cell Density. Week 12 visit
Secondary Outcome
Measure Time Frame
Improvement in Histological Grade of Gastric Carcinoids/ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy Week 12 visit
Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate Week 2 visit (baseline) and Week 6 visit
Decrease in ECL Cell-specific Products Assessed by Quantitative PCR Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Safety and Tolerability Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Circulating Plasma Concentration of Gastrin Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate Week 2 visit (baseline) and Week 6 visit
Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output Week 2 visit (baseline) and Week 6 visit
Enrollment 3
Condition
Intervention

Intervention Type: Drug

Intervention Name: YF476

Description: Gastrin receptor antagonist

Arm Group Label: Eligible patients

Other Name: Netazepide

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.

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Verification Date

2021-01-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Eligible patients

Type: Experimental

Description: 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.

Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

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