A Study of Napabucasin Plus Nab-Paclitaxel With Gemcitabine in Adult Patients With Metastatic Pancreatic Adenocarcinoma

Inclusion Criteria

• Written, signed consent for trial participation must be obtained from the patient appropriately in accordance with applicable International Conference on Harmonization (ICH) guidelines and local and regulatory requirements prior to the performance of any study specific procedure.
• Must have histologically or cytologically confirmed advanced pancreatic ductal adenocarcinoma (PDAC) that is metastatic. The definitive diagnosis of metastatic PDAC will be made by integrating the histopathological data within the context of the clinical and radiographic data. Patients with islet cell neoplasms are excluded.
• Must not have previously received chemotherapy or any investigational agent for the treatment of PDAC. A fluoropyrimidine or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed for as long as last dose was administered > 6 months prior to randomization and no lingering toxicities are present.
• Nab-paclitaxel with gemcitabine therapy is appropriate for the patient and recommended by the Investigator.
• Patient has one or more metastatic tumors evaluable by CT scan with contrast (or MRI, if patient is allergic to CT contrast media) per RECIST 1.1. Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as necessary to document all sites of disease must be performed within 14 days prior to randomization. Qualifying scans performed as part of standard of care prior to patient signature of the study informed consent will be acceptable as baseline scanning as long as scanning is performed 12 weeks.
• Must be ≥ 18 years of age. Due to increased risk of sepsis in patients >80 years old, candidate patients in this age group should be thoroughly evaluated prior to study randomization to ensure they are fit to receive chemotherapy. In addition to all of the inclusion/exclusion criteria listed, clinical judgment should be used regarding patients' susceptibility to infection (including but not limited to presence of ascites or diabetes mellitus increasing risk of infection). Furthermore, the expected stability of their performance status while receiving repeat weekly chemotherapy cycles should be given special attention. Patients in this age group should not be randomized on the study should there be any hesitation on any of these considerations.
• For male or female patients of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 180 days after the final dose of nab-paclitaxel and gemcitabine or for 30 days for female patients and for 90 days for male patients, after the final napabucasin dose if nab-paclitaxel and gemcitabine were not administered.
• Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 5 days prior to randomization.
• Patient has adequate biological parameters as demonstrated by the following blood counts at baseline (obtained 1.5 x 10^9/L
• Platelet count > 100, 000/mm^3 (100 x 10^9/L). Must not have required transfusion of platelets within 1 week of baseline platelet count assessment.
• Hemoglobin (HgB) > 9 g/dL. Must not have required transfusion of red blood cells within 1 week of baseline Hgb assessment.
• Patient has the following blood chemistry levels at baseline (obtained ULN and 60 mL/min/1.73 m^2 for patients with serum creatinine levels above or below the institutional normal value. If using creatinine clearance, actual body weight should be used for calculating creatinine clearance (eg. Using the Cockcroft-Gault formula). For patients with a Body Mass Index (BMI) > 30 kg/m^2, lean body weight should be used instead.
• Patient not on anticoagulation has acceptable coagulation studies (obtained 18 kg/m^2 and body weight of > 40 kg with serum albumin > 3 g/dL.
• Baseline laboratory evaluations must be done within 14 days prior to randomization and some must be repeated 7 days prior to screening.
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