Safety, Pharmacokinetics and Efficacy of AXP107-11 in Combination With Standard Gemcitabine (Gemzar®) Treatment in Patients With Locally Advanced or Metastatic, Unresectable, Adenocarcinoma of the Pancreas, Stage III-IV: A Prospective, Open Label, Multi-centre, Sequential Phase Ib/IIa Study

Fecha de inicio: 1 de noviembre de 2010

Inclusion Criteria: 1. Age ≥ 18 years at the time of signing the informed consent 2. Histologically confirmed adenocarcinoma of the pancreas 3. Metastatic or locally advanced, unresectable disease stage III-IV. 4. Measurable disease according to the international criteria proposed by the Response Evaluation Criteria in Solid tumors (RECIST) for target lesions 5. Karnofsky Performance Status ≥ 70 at study entry (Appendix 18.4). 6. Life expectancy of more than three months 7. Negative pregnancy test for female patients 8. For fertile women, willingness to perform double-barrier contraception during study and for four weeks after last treatment 9. Able and willing to sign the informed consent form Exclusion Criteria: 1. Previous or ongoing severe supraventricular or ventricular arrhythmia 2. Previous or ongoing coagulation or bleeding disorder (PTT \> 1.5 x ULN) 3. HIV infection 4. Known hypersensitivity to any component of the AXP107-11 formulation or gemcitabine 5. Previous or ongoing significant liver pathology (other than metastases) and/or liver function disorders 6. Previous or ongoing significant chronic renal dysfunction 7. Previous or ongoing malignancy other than pancreatic cancer \< five years prior to enrolment, except basal cell carcinoma treated locally 8. Cardiovascular disease, New York Heart Association (NYHA) classification III or IV16 9. Severe pulmonary obstructive or restrictive disease 10. Acute or chronic inflammation (autoimmune or infectious) 11. Significant active/unstable non-malignant disease likely to interfere with study assessments 12. Laboratory tests (hematology, chemistry) outside specified limits: * WBC ≤ 3 x 10³/mm³ * ANC ≤ 1.5 x 10³/mm³ * Platelets ≤ 100.000/mm³ * Hb ≤ 9.0 g/dl (≤ 5.6 mmol/l) * PT/PTT \> 1.5 x ULN * Serum creatinine \> 130 μmol/l) or clearance \< 60 ml/min * AST and/or ALT \> 3 x ULN with the exception of patients with liver metastasis (\> 5 x ULN) * Alkaline phosphatase \> 3 x ULN * Total bilirubin \> 3 x ULN 13. Immunotherapy within six weeks prior to enrolment. 14. Any chemotherapeutical treatment for pancreatic adenocarcinoma before enrolment 15. Any radiotherapy for pancreatic adenocarcinoma before enrolment except for treatment of bone metastases if target lesions are not included in the irradiated field 16. Major surgery within four weeks prior to enrolment 17. Pregnant or nursing woman 18. Participations in other interventional clinical study within four weeks of enrolment