YF476 and Type II Gastric Carcinoids

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02454075
Recruitment Status : Enrolling by invitation
First Posted : May 27, 2015
Last Update Posted : October 18, 2017
National Institutes of Health (NIH)
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Zollinger-Ellison Syndrome Drug: YF476 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Trial of YF476, a Gastrin Antagonist, in Patients With Type II Gastric Carcinoids Associated With Zollinger-Ellison Syndrome
Study Start Date : April 2011
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : January 2024

Arm Intervention/treatment
Experimental: Eligible patients
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.
Drug: YF476
Gastrin receptor antagonist
Other Name: Netazepide

Primary Outcome Measures :
  1. Regression of gastric carcinoids and/or ECL cell hyperplasia defined by physical measurements taken during endoscopy [ Time Frame: Up to 10 years ]
    Regression is defined as a 25% reduction in the size / number of endoscopically evident type II gastric carcinoids; or a reduction of 25% in the gastric ECL cell density.

Secondary Outcome Measures :
  1. Improvement in histological grade of gastric carcinoids/ECL cell hyperplasia defined by physical measurements taken during endoscopy [ Time Frame: Up to 10 years ]
    Reduction in the histological grade of the carcinoids/hyperplasia when compared to baseline.

  2. Level of gastrin and chromogranin A (CgA) biomarkers measured in blood samples [ Time Frame: Up to 10 years ]
    Reduction in the levels of circulating gastrin and CgA biomarkers.

  3. Control of gastric acid secretion assessed by changes in drug-controlled gastric acid analysis (acid control study) [ Time Frame: Up to 10 years ]
    Assessed by changes in drug-controlled gastric acid analysis.

  4. Decrease in ECL cell-specific products assessed by quantitative PCR [ Time Frame: Up to 10 years ]
    Assessed by quantitiative PCR.

  5. Improvement in reflux/dyspepsia symptoms using the GERD-HRQL instrument [ Time Frame: Up to 10 years ]
    Assessed by the GERD-HRQL instrument.

  6. Safety and tolerability by monitoring adverse events [ Time Frame: Up to 10 years ]
    The treatment is safe and well tolerated when added to existing treatments for ZES.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 staus >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.

Responsible Party: Trio Medicines Ltd. Identifier: NCT02454075     History of Changes
Obsolete Identifiers: NCT01322542
Other Study ID Numbers: T-010
11-DK-0114 ( Other Identifier: NIH number )
First Posted: May 27, 2015    Key Record Dates
Last Update Posted: October 18, 2017
Last Verified: October 2017

Keywords provided by Trio Medicines Ltd.:
gastric carcinoids
Zollinger-Ellison syndrome

Additional relevant MeSH terms:
Carcinoid Tumor
Zollinger-Ellison Syndrome
Pathologic Processes
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Paraneoplastic Endocrine Syndromes
Paraneoplastic Syndromes
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Peptic Ulcer
Duodenal Diseases
Intestinal Diseases
Stomach Diseases
Carcinoma, Islet Cell
Pancreatic Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Pancreatic Diseases