YF476 and Type II Gastric Carcinoids
Condition: Zollinger-Ellison Syndrome
MeSH terms: Carcinoid Tumor; Zollinger-Ellison Syndrome; Gastrinoma; Syndrome
Intervention: YF476
Intervention description: Gastrin receptor antagonist
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: YF476; netazepide; gastric carcinoids; Zollinger-Ellison syndrome

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.