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

This is a randomized, open-label, multi-center, phase 3 study of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine for adult patients with Metastatic Pancreatic Ductal Adenocarcinoma.

Drug: Napabucasin. Napabucasin will be administered orally, twice daily, with doses separated by approximately 12 hours.

Drug: Nab-paclitaxel. Nab-paclitaxel 125 mg/m\^2 immediately followed by gemcitabine 1000 mg/m\^2 will be administered on Days 1, 8 and 15 of every 28-day cycle via intravenous infusion.

Drug: Gemcitabine. Nab-paclitaxel 125 mg/m\^2 immediately followed by gemcitabine 1000 mg/m\^2 will be administered on Days 1, 8 and 15 of every 28-day cycle via intravenous infusion.

Arm 1: Napabucasin plus Nab-paclitaxel with Gemcitabine (experimental): Patients randomized to this arm will receive napabucasin administered orally, twice daily in combination with weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.

Arm 2: Nab-paclitaxel with Gemcitabine (active comparator): Patients randomized to this arm will receive weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.

Overall Survival. To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Overall Survival of patients with metastatic pancreatic ductal adenocarcinoma. Time frame: From 4 weeks after the patient has been off study therapy, every 4 weeks thereafter for 6 months, then every 3 months thereafter until death, the study closes or 3 years since treatment discontinuation..

Progression Free Survival. Time frame: From date of randomization, every 8 weeks, until the date of first documented objective disease progression, up to 36 months.

Disease Control Rate. Time frame: From date of randomization, every 8 weeks, until the date of first documented objective disease progression, up to 36 months.

Overall Response Rate. Time frame: From date of randomization, every 8 weeks, until the date of first documented objective disease progression, up to 36 months.

Number of Patients With Adverse Events. Time frame: Every 1-2 weeks from date of screening until protocol treatment discontinuation. Following permanent protocol treatment discontinuation, every 8 weeks, starting with the 4 week post-protocol treatment discontinuation visit, up to 36 months..

Mean Change From Baseline for Global Quality of Life (QoL) at 8 Weeks.. Time frame: 8 weeks.

Inclusion Criteria: 1. 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. 2. 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. 3. 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. 4. Nab-paclitaxel with gemcitabine therapy is appropriate for the patient and recommended by the Investigator. 5. 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 \< 14 days prior to randomization. 6. Must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1, assessed within 14 days prior to randomization. Two observers qualified to perform assessment of the performance status will be required to perform this assessment. If discrepant, the one with the most deteriorated performance status will be considered true. 7. Must have life-expectancy of \> 12 weeks. 8. 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). …

Enrollment: 1134 participants (actual).