A Phase Ib/IIa, Multicentre, Randomised, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate the Safety and Pharmacokinetics of Z-360 in Subjects with Unresectable Advanced Pancreatic Cancer in Combination with Gemcitabine Treatment

INTERVENTION: Product Name: Z‐360 Pharmaceutical Form: Coated tablet Current Sponsor code: Z‐360 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 60‐ Pharmaceutical form of the placebo: Coated tablet Route of administration of the placebo: Oral use Trade Name: Gemzar Product Name: Gemzar Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: Gemcitabine Concentration unit: g gram(s) Concentration type: equal Concentration number: 1‐ CONDITION: Pancreatic cancer PRIMARY OUTCOME: Main Objective: 1. To evaluate the safety of two doses of Z‐360 with gemcitabine administration for subjects with unresectable advanced pancreatic cancer in order to determine the optimal dosage for Phase II study.; 2. To determine the pharmacokinetic parameters of Z‐360 in subjects with pancreatic cancer. Primary end point(s): Completion of the 12‐week treatment and 4‐week follow up period. Secondary Objective: 1. To evaluate the drug‐drug interaction between Z‐360 and gemcitabine.; 2. To evaluate the efficacy of Z‐360 by the objective tumour response rate.; 3. To evaluate the effect of Z‐360 on subject quality of life as measured by a; quality of life questionnaire. INCLUSION CRITERIA: • Age 20 years and over. • Provide written informed consent. • In the investigator’s opinion, the subject has the ability to co‐operate with the treatment and follow up procedures. • Subjects with unresectable locally advanced (histologically/cytologically verified) or metastatic pancreatic cancer. • Subjects must have at least one measurable lesion. • No other primary neoplasms apart from pancreatic cancer. • Life expectancy of at least 3 months. • Karnofsky Performance Status of =70%. • Adequate liver and renal function as defined by: serum creatinine (=133 µmol/L); total bilirubin levels (=34.2 µmol/L); AST or ALT levels =3 times the upper limit of the reference range (or <5 times in the presence of liver metastases). • Adequate bone marrow function defined by a white blood cell (WBC) count of =3.5 x 109/L, an absolute neutrophil (ANC) count of =1.5 x 109/L, a platelet count of =100 x 109/L and a haemoglobin level