YF476 and Type II Gastric Carcinoids

Phase 2TerminatedNCT02454075

Trio Medicines Ltd.3 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Zollinger-Ellison Syndrome

Interventions

YF476DRUG

Gastrin receptor antagonist

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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

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.

Time frame: Week 12 visit

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

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

Time frame: Week 12 visit

Secondary Outcomes

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

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

Time frame: Week 12 visit

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

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

Time frame: 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

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)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.