A Trial of Cobicistat and Gemcitabine and Nab-Paclitaxel in Patients with Advanced Stage or Metastatic Pancreatic Ductal Adenocarcinoma

Exclusion Criteria

• •4. Eligible for therapy with gemcitabine / nab-paclitaxel according to standard of care / local therapeutic standard (in any palliative therapy line)
• •5. Performance score ECOG 0-2
• •6. Adequate organ function defined as:
• •1. Adequate hematologic function (WBC ≥3000/µL, absolute neutrophil count ≥1500/µL, platelets ≥100.000/µL, hemoglobin ≥8 g/dL)
• •2. Adequate renal function (estimated glomerular filtration rate ≥30 mL/min)
• •3. Adequate liver function (serum bilirubin ≤1.5 x ULN, AST/ALT ≤2.5 x ULN, or 5 x ULN if hepatic metastases are present)
• •4. Prothrombintime (PT) \<1.1 ULN, partial thromboplastin time \<1.1 ULN, INR \<1.1 ULN.
• •7. Use of reliable contraception with a Pearl Index \<1% (i.e. two independent effective contraceptive methods) during the trial and for two weeks after the last administration of trial medication in men or women of child bearing potential (WOCBP).
• •8. Measurable disease according to RECIST 1.1 criteria.
• •9. Patient willing to undergo tumor biopsy. This requires a tumor lesion accessible for a biopsy. In patients without an accessible tumor lesion the patient may be enrolled and tumor biopsy waived after discussion with the sponsor's medical representative.
• •10. Available CT scan of thorax and abdomen not older than 30 days before start of treatment (day 1 of cycle 1). Patients that cannot have a CT scan because of medical reasons (e.g. allergy to contrast dye) may be eligible after MRIs as per standard of care to stage the patient and after documented consultation with the sponsor.
• •11. Ability to understand character, consequences and requirements of the clinical trial and to comply with the study protocol and dosing regimen.
• •1. Presence of brain metastases, unless previously treated and well-controlled for at least 3 months (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart).
• •2. Testing positive against human immunodeficiency virus (HIV) or history thereof
• •3. Active hepatitis C virus (HCV) infection (patients with status post-infection after eradication through antiviral therapy are eligible)
• •4. Uncontrolled hepatitis B virus (HBV) infection (\<3 months of treatment with a nucleotide analogue and/or \>100 HBV-DNA particles)
• •5. Pre-existing, clinically significant peripheral neuropathy, defined as CTCAE grade 2 or higher neurosensory or neuromotor toxicity, regardless of etiology