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

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.

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.