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

Completed · Phase 3

Conditions studied: Carcinoma, Pancreatic Ductal

In brief

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.

Key facts

Study ID

NCT02993731

Run by

Sumitomo Pharma America, Inc.

People needed

1134

Starts

2016-12-01

Expected to finish

2020-03-01

Last updated by the study team

2023-11-15

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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 < 14 days prior to randomization.
• 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.
• Must have life-expectancy of > 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 < 14 days prior to randomization; laboratory testing performed as part of standard of care prior to patient signature of informed consent for the study will be acceptable as baseline laboratory work as long as testing is performed < 14 days prior to randomization):
• Absolute neutrophil count (ANC) > 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 < 14 days prior to randomization; laboratory testing performed as part of standard of care prior to patient signature of informed consent for the study will be acceptable as baseline laboratory work as long as testing is performed < 14 days prior to randomization):
• AST (SGOT) and ALT (SGPT) ≤ 2.5 × institutional upper limit of normal (ULN) [≤ 5 × ULN in presence of liver metastases]
• Total bilirubin ≤ 1.5 x institutional ULN. If total bilirubin is > ULN and < 1.5 x ULN, it must be non-rising for at least 7 days.
• Serum creatinine within normal limits or calculated clearance > 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 < 14 days prior to randomization; laboratory testing performed as part of standard of care prior to patient signature of informed consent for the study will be acceptable as baseline laboratory work as long as testing is performed < 14 days prior to randomization) as demonstrated by prothrombin time (PT) and partial thromboplastin time (PTT) below or within normal limits (+15%).
• Patients on anticoagulation must have coagulation values within the therapeutic range appropriate for the anti-coagulation indication.
• Patient has no clinically significant abnormalities on urinalysis results (obtained < 14 days prior to randomization; laboratory testing performed as part of standard of care prior to patient signature of informed consent for the study will be acceptable as baseline laboratory work as long as testing is performed < 14 days prior to randomization).
• Patient must have adequate nutritional status with Body Mass Index (BMI) > 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 < 72 hours prior to randomization.
• Patients requiring biliary stent placement must have biliary stent placed > 7 days prior to screening.
• Pain symptoms should be stable (of tolerable Grade 2 or less).

You may not qualify if…

• Patients with no evidence of metastatic disease as well as patients with a local recurrence following surgical resection of primary lesion.
• Patient has experienced a decline in ECOG performance status between Baseline visit and within 72 hours prior to randomization.
• Patient has a > 20% decrease in serum albumin level between Baseline visit and within 72 hours prior to randomization.
• Patient has a > 10% decrease in weight between Baseline visit and within 72 hours prior to randomization.
• Any prior anti-cancer chemotherapy, biologic or investigational therapy for PDAC.
• Patients receiving immunotherapy for non-cancer related treatment within < 4 weeks of first planned dose of study treatment will be excluded.
• 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.
• Major surgery within 4 weeks prior to randomization.
• Any known brain or leptomeningeal metastases are excluded, even if treated.
• Patients with clinically significant ascites or pleural effusions.
• Women who are pregnant or breastfeeding. Women should not breastfeed while taking study treatment and for 4 weeks after the last dose of napabucasin or while undergoing treatment with nab-paclitaxel and gemcitabine and for 180 days after the last dose of nab-paclitaxel and gemcitabine.
• Gastrointestinal disorder(s) which, in the opinion of the Principal Investigator, would significantly impede the absorption of an oral agent (e.g. active Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection).
• Unable or unwilling to swallow napabucasin capsules daily.
• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.
• History of cardiac disease: congestive heart failure (CHF) > New York Heart Association (NYHA) Class II; active coronary artery disease, myocardial infarction or coronary stenting within 6 months prior to randomization; unevaluated new onset angina within 3 months or unstable angina (angina symptoms at rest) or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).
• Current uncontrolled hypertension (systolic blood pressure [BP] > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management) as well as prior history of hypertensive crisis or hypertensive encephalopathy.
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection, symptomatic peripheral vascular disease including claudication, Leo Buerger's disease). Treated peripheral vascular disease that is stable for at least 6 months is allowed.
• Evidence of bleeding diathesis or clinically significant coagulopathy.
• Major surgical procedure (including open biopsy, significant traumatic injury, etc.) within 28 days, or anticipation of the need for major surgical procedure during the course of the study as well as minor surgical procedure (excluding placement of a vascular access device or bone marrow biopsy) within 7 days prior to randomization.
• Patients with clinically significant abnormalities on urinalysis at < 14 days prior to randomization.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization.
• Ongoing serious, non-healing wound, ulcer, or bone fracture.
• Known infection with Human Immunodeficiency Virus (HIV), and/or active infection with hepatitis B, or hepatitis C.
• History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.
• History of hemolytic-uremic syndrome.

Where it is running

• Clearview Cancer Institute (CCI) — Huntsville, Alabama, United States
• Banner MD Anderson Cancer Center — Gilbert, Arizona, United States
• Mayo Clinic — Phoenix, Arizona, United States
• Highlands Oncology Group — Fayetteville, Arkansas, United States
• Comprehensive Blood and Cancer Center — Bakersfield, California, United States
• Los Angeles Hematology Oncology Medical Group — Los Angeles, California, United States
• University of Southern California — Los Angeles, California, United States
• St. Joseph Hospital of Orange — Orange, California, United States
• Torrance Health Association DBA Torrance Memorial — Redondo Beach, California, United States
• UC Davis — Sacramento, California, United States
• UCLA Medical Center Santa Monica Hematology And Oncology — Santa Monica, California, United States
• Kaiser Permanente - Vallejo Medical Center — Vallejo, California, United States
• Norwalk Hospital The C Anthony and Jean Whittingham Cancer Center — Norwalk, Connecticut, United States
• The C Anthony and Jean Whittingham Cancer Center — Norwalk, Connecticut, United States
• Helen F. Graham Cancer Center — Newark, Delaware, United States
• Georgetown University Medical Center (GUMC) — Washington D.C., District of Columbia, United States
• Florida Cancer Specialists & Research Institute — Fort Myers, Florida, United States
• Memorial Regional Hospital — Hollywood, Florida, United States
• Mayo Clinic Cancer Center — Jacksonville, Florida, United States
• Cancer Specialists of North Florida — Jacksonville, Florida, United States
• Sylvester Comprehensive Cancer Center — Miami, Florida, United States
• Mount Sinai Medical Center — Miami Beach, Florida, United States
• UF Health Cancer Center - Orlando Health — Orlando, Florida, United States
• Florida Cancer Specialists North — St. Petersburg, Florida, United States
• UAB Comprehensive Cancer Center — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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