Paricalcitol Addition to Chemotherapy in Patients With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma

Inclusion Criteria: 1. Willing and able to provide written informed consent. 2. Ability to comply with the protocol. 3. Aged ≥ 18 years; male or female. 4. Histologically or cytologically confirmed metastatic (stage IV) pancreatic ductal adenocarcinoma. 5. Karnofsky performance status ≥70. 6. At least one lesion that can be measured accurately at baseline as ≥10mm in the longest diameter (except lymph nodes which must have a short axis ≥15mm) with CT/MRI and which is suitable for repeated measurements per RECIST v1.1 7. Adequate haematological and end-organ function, as per the local institutions reference ranges, within 21 days prior to day 1 of cycle 1 of treatment defined by the following: 1. Haematology: ANC \>1.5 x 109/L (\>1500 cells / mm3); Platelet count \> 100 x 109/L (\>100,000 cells/mm3); haematocrit level \>27% for females or \>30% for males 2. Coagulation: INR and aPTT ≤1.5 x ULN. 3. Biochemistry: serum creatinine \< 1.5mg/dl, bilirubin \< 1.5 x ULN; AST / ALT ≤ 2.5 x ULN (or ≤ 5 x ULN in the presence of liver metastasis) calculated creatinine clearance ≥ 50ml/min (as measured by Cockcroft \& Gault) 8. Life expectancy ≥ 12 weeks. 9. Women of childbearing potential must agree not to become pregnant (e.g. post-menopausal for at least 1 year, surgically sterile, or using effective contraception) for the duration of the study and for 1 month after last dose of study treatment. Women of child bearing potential must have a negative serum or urine pregnancy test within 14 days of Cycle 1 Day 1 (preferably as close to the study treatment day as possible). Both male and female patients of reproductive potential must agree to use effective contraception from 2 weeks before the start of study treatment and until 6 month (female participants) or 6 months (male participants) after completion of treatment (as per protocol section 6.10.5). 10. Tumour sites amenable to repeated biopsies. 11. Willingness to undergo paired tumour biopsies during the trial Exclusion Criteria: 1. Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatments in the adjuvant setting with gemcitabine and/or 5-FU or gemcitabine administered as a radiation sensitizer are allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present. In exceptional circumstances, if a patient has received paclitaxel protein bound and gemcitabine as first line chemotherapy for metastatic disease in exactly the same way as mandated in the current trial, they can be considered eligible to be enrolled directly to the add on paricalcitol component of the trial. 2. Palliative surgery and/or radiation treatment less than 4 weeks prior to initiation of study treatment. 3. Exposure to any investigational agent within 4 weeks prior to initiation of study treatment. 4. Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within 28 days of Cycle 1 Day 1). 5. History of other malignancies (except cured basal or squamous cell carcinoma, superficial bladder cancer, prostate cancer in active surveillance, or carcinoma in situ of the cervix) unless documented free of cancer for ≥2 years. 6. Current, serious, clinically significant cardiac arrhythmias as determined by the investigator. 7. History of HIV infection. 8. Active, clinically significant serious infection requiring treatment with antibiotics, antivirals or anti-fungals (see Section 6.10). 9. History of symptomatic genitourinary stones (e.g. kidney stones) within 12months of Cycle 1 Day 1. 10. Pre-existing, clinically significant peripheral neuropathy ≥ G2 11. Hypersensitivity to the active study drug substance or to any of its excipients as listed in section 6 of the SmPC of each study drug. 12. Patients with a history of pneumonitis 13. Patients with a history of a hearing impairment 14. Patients who have received any live vaccines within 4 weeks prior to trial registration 15. Patient is on prohibited concurrent medication (see Section 6.10). In particular, vitamin D and calcium supplements must be stopped at the time of enrolment and for the duration of study treatment. 16. Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of study treatment, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent. 17. Female patients who are pregnant or nursing.