Phase I/II Study of LDE225 With Gemcitabine and Nab-paclitaxel in Patients With Pancreatic Cancer

Inclusion Criteria: 1. Patients must provide written informed consent according to International Conference on Harmonisation of technical requirements for registration og pharmaceuticals for human use (ICH)/Good cClinical Practice (GCP), and national/local regulations prior to any screening procedures. 2. Male or female adult patients (\> 18 years) 3. Patients with histologically/cytologically confirmed diagnosis of pancreatic ductal adenocarcinoma. 4. a. Phase I: patients with non resectable or metastasized pancreatic ductal adenocarcinoma. b. Phase II: patients with non resectable or metastasized pancreatic ductal adenocarcinoma not pre-treated with chemotherapy or radiotherapy, unless adjuvant treatment with gemcitabine \> 6 months prior to inclusion. 5. Measurable disease as assessed by RECIST 1.1 (Response Evaluation Criteria In Solid Tumors) . 6. ECOG (Eastern Cooperative Oncology Group) (WHO) performance status 0-2 7. Patient has adequate bone marrow and organ function . Patient is able to swallow and retain oral medication 9\. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; Exclusion Criteria: 1. History of hypersensitivity to LDE225, or to drugs of similar chemical classes. 2. Patient has received previous treatment with smoothened inhibitors. 3. Patients with known CNS (Central Nervous System) metastases or a primary CNS malignancy. 4. Patients who have neuromuscular disorders or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as HMG CoA (3-hydroxy-3-methyl-glutaryl Coenzyme A) inhibitors (statins), clofibrate and gemfibrozil. 5. Patients who are planning on embarking on new physical activities, such as strenuous exercise, that can result in significant increases in plasma CK (Creatine Kinase) levels while on study treatment. 6. Patients who require the use of coumarin derivates cannot be enrolled as LDE225 is a competitive inhibitors of CYP2C9 based on in-vitro data. 7. Patients with chronic use of corticosteroids 8. Patients who are not willing to avoid consumption of Seville oranges, grapefruit or grapefruit juice grapefruit hybrids, pomelos and exotic citrus fruits during the entire study and preferably 7 days before the first dose of study medications, due to potential CYP3A4 interaction with the study medications. 9. Patients who are not willing to stop taking herbal medications at least 7 days prior to the first dose of study treatment. 10. Patient is currently being treated with drugs known to be strong inhibitors or inducers of CYP3A4/5, which cannot be discontinued or switched to a different medication 7 days prior to starting study treatment and for the duration of the study.. 11. Current medical history of the following: * History of or presence of clinically significant uncontrolled ventricular or atrial tachyarrhythmia * Clinically significant resting bradycardia (\< 45 beats per minute) or any primary of secondary heart block * History of unstable angina pectoris * Clinically significant cardio-vascular disease (e.g. congestive heart failure NYHA Class III-IV (New York Heart Association), atherosclerosis, labile hypertension or uncontrolled hypertension 12. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive HCG (Human Chorionic Gonadotropin) laboratory test 13. Patients who are not willing to apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment. 14. Sexually active males who are unwilling to use a condom during intercourse while taking drug and for 6 months after stopping investigational medications and agree not to father a child in this period. Patients who in the investigators' opinion may be unwilling, unable or unlikely to comply with requirements of the study protocol 15. Patient is currently receiving increasing or chronic treatment with corticosteroids ((≥ the anti-inflammatory potency of 4mg dexamethasone) or another immunosuppressive agent. 16. Patient has been treated with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) ≤ 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated before enrollment, may be continued 17. Patient who has received targeted therapy or immunotherapy ≤ 3 weeks (6 weeks for monoclonal antibodies) prior to starting study drug or who have not recovered to grade 1 or better from related side effects of such therapy 18. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of LDE225 (e.g., ulcerative colitis, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) 19. Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment contraindicate patient participation in the clinical study. 20. HIV-positive patients on combination antiretroviral therapy. 21. Patients who in the investigators' opinion may be unwilling, unable or unlikely to comply with requirements of the study protocol