YF476 and Type II Gastric Carcinoids

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Trio Medicines Ltd.
ClinicalTrials.gov Identifier:
NCT02454075
First received: May 13, 2015
Last updated: May 21, 2015
Last verified: May 2015
  Purpose
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 Intervention Phase
Zollinger-Ellison Syndrome
Drug: YF476
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Trio Medicines Ltd.:

Primary Outcome Measures:
  • Regression of gastric carcinoids and/or ECL cell hyperplasia defined by physical measurements taken during endoscopy [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    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:
  • Improvement in histological grade of gastric carcinoids/ECL cell hyperplasia defined by physical measurements taken during endoscopy [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Reduction in the histological grade of the carcinoids/hyperplasia when compared to baseline.

  • Level of gastrin and chromogranin A (CgA) biomarkers measured in blood samples [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Reduction in the levels of circulating gastrin and CgA biomarkers.

  • Control of gastric acid secretion assessed by changes in drug-controlled gastric acid analysis (acid control study) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Assessed by changes in drug-controlled gastric acid analysis.

  • Decrease in ECL cell-specific products assessed by quantitative PCR [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Assessed by quantitiative PCR.

  • Improvement in reflux/dyspepsia symptoms using the GERD-HRQL instrument [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Assessed by the GERD-HRQL instrument.

  • Safety and tolerability by monitoring adverse events [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The treatment is safe and well tolerated when added to existing treatments for ZES.


Estimated Enrollment: 30
Study Start Date: April 2011
Estimated Study Completion Date: January 2024
Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Responsible Party: Trio Medicines Ltd.
ClinicalTrials.gov Identifier: NCT02454075     History of Changes
Obsolete Identifiers: NCT01322542
Other Study ID Numbers: T-010  11-DK-0114 
Study First Received: May 13, 2015
Last Updated: May 21, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Trio Medicines Ltd.:
YF476
netazepide
gastric carcinoids
Zollinger-Ellison syndrome

Additional relevant MeSH terms:
Gastrinoma
Zollinger-Ellison Syndrome
Adenocarcinoma
Carcinoma
Carcinoma, Islet Cell
Digestive System Diseases
Digestive System Neoplasms
Duodenal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Pancreatic Diseases
Pancreatic Neoplasms
Paraneoplastic Endocrine Syndromes
Paraneoplastic Syndromes
Peptic Ulcer
Stomach Diseases

ClinicalTrials.gov processed this record on May 24, 2016