Multicenter Phase II/III Clinical Study of Lipoplatin plus Gemcitabine as First-Line Treatment in Inoperable, Locally Advanced or Metastatic Pancreatic Cancer.

INTERVENTION: Product Name: Lipoplatin Product Code: Lipoplatin Pharmaceutical Form: Intravenous infusion INN or Proposed INN: cisplatin CAS Number: 15663‐27‐1 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 3‐ CONDITION: locally advanced or metastatic inoperable adenocarcinoma of the pancreas with no prior chemotherapy ; MedDRA version: 8.1 Level: LLT Classification code 10033606 Term: Pancreatic cancer non‐resectable PRIMARY OUTCOME: Main Objective: For Phase II; • To assess the Disease Control Rate DCR (CR+PR+SD) ; For Phase III; Primary endpoint: ; • To compare overall survival (OS); Primary end point(s): Phase ??:; • Disease Control Rate (DCR) is defined as the sum of Complete Response (CR) plus Partial Response (PR) plus Stable Disease (SD) at week 9 of treatment. Evaluation of response is based on the Response Evaluation Criteria in Solid Tumors (RECIST, see Appendix II), with confirmation at 4 weeks. ; ; DCR will be used instead of Objective Response Rate (ORR=Complete Response+Partial Response), as it is a more helpful measure in cancers difficult to evaluate or with only minor response to treatment, as is the case for pancreatic cancer. Although DCR at first post‐baseline disease evaluation may be more sensitive to initial differences in tumor growth rate, most bibliographic references use the specific time, which was therefore chosen for the current study. ; ; Phase III:; • Overall Survival (OS) is defined as the time from randomisation until death from any cause. ; ; Secondary Objective: For Phase II; • To assess the 1‐year survival; • To assess toxicity; For Phase III; • To compare progression‐free survival time (PFS).; • To compare objective response rate (ORR); • To compare quality of life (Q?L); • To compare safety; ; INCLUSION CRITERIA: • Adult male or female 18‐70 years old. • Histologically or cytologically confirmed diagnosis of locally advanced or metastatic inoperable adenocarcinoma of the pancreas • Presence of at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors. (RECIST, see Appendix II). • WHO performance status (PS) 0‐1 (Appendix I). • Life expectancy of at least 3 months. • At least 4 weeks since prior major surgery, with full recovery from all side effects. • Adequate bone marrow function (defined as peripheral absolute granulocyte count > 2000/mm3 and platelet count = 140000/mm3). • Adequate liver function (bilirubin = 2 mg/dl, SGOT or SGPT no greater than 2.5 x ULN or 4 x ULN in case of hepatic metastasis). • Adequate renal function (creatinine = 1.5 mg/dl, creatinine clearance = 60ml/min). Clearance to be measured after 24‐hour urine collection, or calculated by the following formulas: CrClmale=[(140‐age)*(wt. as