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

Carcinoma, Pancreatic Ductal Clinical Trial

— CanStem111P  

Official title:

A Phase III Study of BBI-608 Plus Nab-Paclitaxel With Gemcitabine in Adult Patients With Metastatic Pancreatic Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02993731
• Other study ID #: CanStem111P
• Status: Completed
• Phase: Phase 3
• Start date: December 2016
• Est. completion date: March 2020

Study information

• Verified date: November 2023
• Source: Sumitomo Pharma America, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1134
• Est. completion date: March 2020
• Est. primary completion date: March 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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). 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.

9. 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.

10. Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 5 days prior to randomization.

11. 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):

1. Absolute neutrophil count (ANC) > 1.5 x 10^9/L

2. 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.

3. Hemoglobin (HgB) > 9 g/dL. Must not have required transfusion of red blood cells within 1 week of baseline Hgb assessment.

12. 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):

1. AST (SGOT) and ALT (SGPT) = 2.5 × institutional upper limit of normal (ULN) [= 5 × ULN in presence of liver metastases]

2. 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.

3. 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.

13. 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.

14. 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).

15. 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.

16. Baseline laboratory evaluations must be done within 14 days prior to randomization and some must be repeated < 72 hours prior to randomization.

17. Patients requiring biliary stent placement must have biliary stent placed > 7 days prior to screening.

18. Pain symptoms should be stable (of tolerable Grade 2 or less).

19. Only patients with available archival tumor tissue must consent to provision of, and Investigator(s) must confirm access to and agree to submit a representative formalin fixed paraffin block of tumor tissue in order that the specific correlative marker assays (Correlative Studies) of this protocol may be conducted. Submission of the tissue does not have to occur prior to randomization. Where local center regulations prohibit submission of blocks of tumor tissue, two 2 mm cores of tumor from the block and 5-20 unstained slides of whole sections of representative tumor tissue are preferred. Where it is not possible to obtain two 2 mm cores of tumor from the block, 5-20 unstained slides of representative tumor tissue are also acceptable. Where no previously resected or biopsied tumor tissue exists or is available, on the approval of the Sponsor/designated CRO, the patient may still be considered eligible for the study.

20. Patient must consent to provision of a sample of blood in order that the specific correlative marker assays (Correlative Studies) may be conducted.

21. Patients must be accessible for treatment and follow up. Patients registered on this trial must receive protocol treatment and be followed at the participating center. This implies there must be reasonable geographical limits placed on patients being considered for this trial. Investigators must ensure that the patients randomized on this trial will be available for complete documentation of the treatment, response assessment, adverse events, and follow-up.

22. Protocol treatment is to begin within 2 calendar days of patient randomization for patients randomized to Arm 1. Patients randomized to Arm 2 must begin protocol treatment within 7 calendar days of randomization.

23. The patient is not receiving therapy in a concurrent clinical study and the patient agrees not to participate in other interventional clinical studies during their participation in this trial while on study treatment. Patients participating in surveys or observational studies are eligible to participate in this study.

Exclusion Criteria:

1. Patients with no evidence of metastatic disease as well as patients with a local recurrence following surgical resection of primary lesion.

2. Patient has experienced a decline in ECOG performance status between Baseline visit and within 72 hours prior to randomization.

3. Patient has a > 20% decrease in serum albumin level between Baseline visit and within 72 hours prior to randomization.

4. Patient has a > 10% decrease in weight between Baseline visit and within 72 hours prior to randomization.

5. Any prior anti-cancer chemotherapy, biologic or investigational therapy for PDAC.

1. Patients receiving immunotherapy for non-cancer related treatment within < 4 weeks of first planned dose of study treatment will be excluded.

2. 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.

6. Major surgery within 4 weeks prior to randomization.

7. Any known brain or leptomeningeal metastases are excluded, even if treated.

8. Patients with clinically significant ascites or pleural effusions.

9. 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.

10. 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).

11. Unable or unwilling to swallow napabucasin capsules daily.

12. 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.

1. 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).

2. 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.

3. 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.

4. Evidence of bleeding diathesis or clinically significant coagulopathy.

5. 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.

6. Patients with clinically significant abnormalities on urinalysis at < 14 days prior to randomization.

7. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization.

8. Ongoing serious, non-healing wound, ulcer, or bone fracture.

9. Known infection with Human Immunodeficiency Virus (HIV), and/or active infection with hepatitis B, or hepatitis C.

10. History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.

11. History of hemolytic-uremic syndrome.

12. History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa).

13. Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders that could compromise the patient's safety or the study data integrity.

13. Known hypersensitivity to gemcitabine, taxanes or any of their excipients, or the patient exhibits any of the events outlined in the Contraindications or Special Warnings and Precautions sections of the product or comparator Summary of Product Characteristics or Prescribing Information. Possible hypersensitivity to napabucasin or one of the excipients which include the azo dyes sunset yellow and allura red.

14. Neurosensory neuropathy > grade 2 at baseline.

15. Uncontrolled chronic diarrhea > grade 2 at baseline.

16. Patients being treated with Warfarin.

17. Patients with active, uncontrolled bacterial, viral or fungal infection(s) requiring systemic therapy

18. Patients with a history of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated by surgery alone or surgery plus radiotherapy with no evidence of disease continuously for > 5 years.

19. Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.

20. Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol, including patients with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol. Patients planning to take a vacation for 14 or more consecutive days during the course of the study are ineligible.

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma, Pancreatic Ductal

Intervention

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

Locations

Country	Name	City	State
Australia	Blacktown Cancer and Haematology Centre	Blacktown
Australia	Border Medical Oncology	East Albury
Australia	Border Medical Oncology	East Albury	New South Wales
Australia	The Austin Hospital	Heidelberg
Australia	Cabrini Hospital	Malvern
Australia	Cabrini Hospital	Malvern	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands
Australia	Prince of Wales Private Hospital	Randwick
Australia	ICON Cancer Care	South Brisbane
Australia	ICON Cancer Care	South Brisbane	South Australia
Australia	Macquarie University Hospital	Sydney	New South Wales
Australia	Macquarie University Hospital	Sydney
Australia	The Tweed Hospital	Tweed Heads
Australia	Sydney Adventist Hospital	Wahroonga
Austria	LKH Universitätsklinikum Graz	Graz
Austria	Landeskrankenhaus Medical University Innsbruck	Innsbruck
Austria	Landeskrankenhaus Feldkirch	Rankweil
Austria	Universitatsklinik far Innere Medizin III	Salzburg
Austria	Medical University Vienna	Vienna
Belgium	ULB Erasme	Bruxelles
Belgium	Antwerp University Hospital	Edegem
Belgium	UZ Ghent	Gent
Belgium	UZ Brussel	Jette
Belgium	UZ Leuven	Leuven
Belgium	CHU de Liege	Liège
Belgium	CHU Dinant Godinne	Yvoir
Canada	Cross Cancer Institute	Edmonton
Canada	Dr. Everett Chalmers Regional Hospital	Fredericton	New Brunswick
Canada	The Atlantic Clinical Cancer Research Unit (ACCRU)	Halifax	Nova Scotia
Canada	Centre Hospitalier de St. Mary	Pointe-Claire	Quebec
Canada	University of Toronto - St. Michael's Hospital	Toronto
Canada	Ciusssmcq	Trois-Rivières	Quebec
China	Beijing Cancer Hospital	Beijing
China	Chinese PLA General Hospital	Beijing
China	Jilin Cancer Hospital	Changchun
China	The first hospital of jilin university	Changchun
China	Fujian Medical University Union Hospital	Fuzhou
China	Cancer Center of Guangzhou Medical University	Guangzhou
China	Guangdong General Hospital	Guangzhou
China	Sir Run Shaw Hospital School of Medicine Zhejiang University	Hangzhou
China	The First Affiliated Hospital Zhejiang University	Hangzhou
China	The Second Affiliated Hospital Zhejiang University	Hangzhou
China	Zhejiang Cancer Hospital	Hangzhou
China	Harbin Medical University Cancer Hospital	Harbin
China	The First Affiliated Hospital of Anhui Medical University	Hefei
China	The Second Affiliated Hospital of Anhui Medical University	Hefei
China	Jiangsu Cancer Hospital	Nanjing
China	The 81 Hospital of the Chinese Peoples Liberation Army	Nanjing
China	The Affiliated Hospital of Qingdao University	Qingdao
China	East Hospital of Tongji University	Shanghai
China	Fudan University Shanghai Cancer Center	Shanghai
China	Huashan Hospital	Shanghai
China	Ren Ji Hospital Shanghai Jiaotong University School of Medicine	Shanghai
China	The First Affiliated Hospital of Soochow University	Suzhou
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin
China	The First Affiliated Hospital of Xian Jiao Tong University	Xian
China	General Hospital of Ningxia Medical University	Yinchuan
China	Henan Cancer Hospital	Zhengzhou
Czechia	Onkologicke oddeleni	Benešov
Czechia	Fakultni nemocnice Brno Interni hematoonkologicka klinika	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	University Hospital Olomouc	Olomouc
Czechia	Onkologické oddelení	Zlín
France	Hôpital Sud - CHU Amiens Picardie	Amiens
France	Hôpital Trousseau, CHRU de Tours	Chambray-lès-Tours
France	Hopital Edourard Herriot	Lyon Cedex 03
France	CHU-Hôtel Dieu	Nantes Cedex 1
France	Centre Antoine Lacassagne	Nice
France	Hopital Europeen Georges Pompidou	Paris
France	Poitiers University Hospital	Poitiers
France	Centre Eugene Marquis	Rennes
France	Clinique Saint Anne	Strasbourg
France	Hopital Civil de strasbourg	Strasbourg
France	Institute de Cancerologie de Lorraine	Vandœuvre-lès-Nancy
Germany	Gesundheitszentrum St. Marien GmbH	Amberg
Germany	University Hospital Bonn	Bonn
Germany	Klinikum Chemnitz	Chemnitz
Germany	Krankenhaus Nordwest	Frankfurt am main
Germany	Medizinische Hochschule	Hannover
Germany	SLK-Kliniken Heilbronn GmbH	Heilbronn
Germany	Universitätsmedizin Mannheim	Mannheim
Germany	Klinikum Bogenhausen	München
Germany	Klinikum Oldenburg AöR - UK für Innere Medizin	Oldenburg
Italy	Fondazione Poliambulanza	Brescia
Italy	Istituto Ricerca e la Cura del Cancro (IRCC)	Candiolo
Italy	AOU Mater Domini	Catanzaro
Italy	Ospedale degli Infermi	Faenza
Italy	Santa Maria de Prato Hospital	Feltre
Italy	IRCCS - Studio e la Cura dei Tumori	Meldola
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	AO SM Misericordia	Perugia
Italy	IRCCS Azienda Ospedaliera S.Maria Nuova	Reggio Emilia
Italy	Ospedale degli Infermi	Rimini
Italy	Dermatological Hospital San Lazzaro	Torino
Italy	ASST Settelaghi	Varese
Japan	University of Tokyo Hospital	Bunkyo-Ku	Tokyo
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	The Cancer Institute Hospital Of JFCR	Koto-Ku	Tokyo
Japan	Kyoto University Hospital	Kyoto
Japan	Shikoku Cancer Center	Matsuyama	Ehime
Japan	Kyorin University Hopsital	Mitaka	Tokyo
Japan	Aichi Cancer Center Hospital	Nagoya	Aichi
Japan	Osaka International Cancer Institute	Osaka
Japan	Saitama Cancer Center	Saitama
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Shizuoka Cancer Center	Shizuoka
Japan	Tochigi Cancer Center	Utsunomiya	Tochigi
Japan	Kanagawa Cancer Center	Yokohama	Kanagawa
Korea, Republic of	Seoul national University Bundang Hospital	Gyeonggi-do
Korea, Republic of	Chonnam National University Hwasun Hospital	Jeongnam
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Netherlands	Medisch Centrum Leeuwarden (MCL)	Leeuwarden
Netherlands	Zuyderland Medical Center	Sittard
Netherlands	University Medical Center Utrecht	Utrecht
Netherlands	Isala Ziekenhuis	Zwolle
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Centrum Onkologii-Instytut im.M.Sklodowskiej-Curie	Gliwice
Poland	Przychodnia Lekarska KOMED	Konin
Poland	Centrum Onkologii Ziemi Lubelskiej	Lublin
Poland	Klinika Chirurgii Onkologicznej	Lublin
Poland	Samodzielny Publiczny Szpital Kliniczny	Poznan
Poland	Wojewodzki Szpital Zespolony	Torun
Portugal	Fundação Champalimaud	Lisboa
Portugal	Hospital da Luz	Lisboa
Portugal	Centro Hospitalar Lisboa Norte	Lisbon
Portugal	Centro Hospitalar do Porto, E.P.E	Porto
Portugal	IPO Porto Francisco Gentil, E.P.E.	Porto
Portugal	Centro Hospitalar Entre Douro e Vouga	Santa Maria Da Feira
Russian Federation	Arkhangelsk Regional Clinical Oncology Dispensary	Arkhangel'sk
Russian Federation	Republican Clinical Oncology Dispensary	Cheboksary
Russian Federation	Llc Evimed	Chelyabinsk
Russian Federation	Railway Clinical Hospital on station Chelyabinsk	Chelyabinsk
Russian Federation	Republic Clinical Oncology Dispensary	Kazan
Russian Federation	Kursk Regional Clinical Oncology Dispensary	Kislino	Kursk
Russian Federation	N.N. Blokhin Russian Cancer Research Center	Moscow
Russian Federation	Privolzhsk District Medical Center	Nizhny Novgorod
Russian Federation	Budgetary Healthcare Institution of Omsk Region	Omsk
Russian Federation	Orenburg Regional Clinical Oncology Dispensary	Orenburg
Russian Federation	Pyatigorsk Oncology Dispensary	Pyatigorsk
Russian Federation	City Clinical Oncology Dispensary	Saint Petersburg
Russian Federation	FSBI "Russian Research Centre of Radiology and Surgical Technologies"	Saint Petersburg
Russian Federation	St.Petersburg Medical Universitet n.a. I.P. Pavlov	Saint Petersburg
Russian Federation	Multi-type clinic 'REAVIZ'	Samara
Russian Federation	National Research Mordovia State University	Saransk
Singapore	National Cancer Centre Singapore	Singapore
Singapore	Tan Tock Seng Hospital	Singapore
Spain	(ICO) Hospital Duran i Reynals	Barcelona
Spain	Hospital Clínico y Provincial de Barcelona	Barcelona
Spain	Hospital Universitario Germans Trias i Pujol	Barcelona
Spain	Hospital Vall d´Hebron	Barcelona
Spain	Centro Integral Oncologico Clara Campal	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Fundacion Alcorcon	Madrid
Spain	Hospital Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Puerta de Hierro	Madrid
Spain	Hospital Regional Universitario de Málaga	Málaga
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung City
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taipei Veterans General Hospital	Taipei City
Taiwan	LinKou Chang Gung Memorial Hospital	Taoyuan
Ukraine	Zaytsev Institute General and Urgent Surgery of National Academy Medical Science of Ukraine	Kharkiv
Ukraine	National Institute of Cancer	Kyiv
United States	UNM Cancer Research and Treatment Center	Albuquerque	New Mexico
United States	University Cancer & Blood Center	Athens	Georgia
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Louisiana Hematology Oncology Associates (LHOA)	Baton Rouge	Louisiana
United States	St. Vincent Frontier Cancer Center	Billings	Montana
United States	UAB Comprehensive Cancer Center	Birmingham	Alabama
United States	Saint Alphonsus Health System	Boise	Idaho
United States	Montefiore Cancer Center	Bronx	New York
United States	Gabrail Cancer Center (GCC) - Canton Facility	Canton	Ohio
United States	UNC Chapel Hill / Lineberger Comprehensive Cancer	Chapel Hill	North Carolina
United States	Charleston Hematology Oncology Associates	Charleston	South Carolina
United States	Medical University of South Carolina (MUSC)	Charleston	South Carolina
United States	Tennessee Oncology Chattanooga	Chattanooga	Tennessee
United States	University of Missouri - Ellis Fischel Cancer Cent	Columbia	Missouri
United States	Columbus Regional Research Institute	Columbus	Georgia
United States	Basset Medical Center	Cooperstown	New York
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	St. Luke's Hospital of Duluth	Duluth	Minnesota
United States	North Shore Hematology Oncology Associates PC	East Setauket	New York
United States	Hematology Oncology Associates of Central New York	East Syracuse	New York
United States	Englewood Hospital and Medical Center	Englewood	New Jersey
United States	NorthShore University Health Systems	Evanston	Illinois
United States	The Everett Clinic	Everett	Washington
United States	San Juan Oncology Associates	Farmington	New Mexico
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Florida Cancer Specialists & Research Institute	Fort Myers	Florida
United States	Parkview Physician Group (PPG)	Fort Wayne	Indiana
United States	The Center for Cancer and Blood Disorders	Fort Worth	Texas
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Southeastern Medical Oncology Center	Goldsboro	North Carolina
United States	Green Bay Oncology, Ltd. - West Green Bay	Green Bay	Wisconsin
United States	HSHS St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	GHS Cancer Institute	Greenville	South Carolina
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Ingalls Cancer Research Center	Harvey	Illinois
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Kaiser Permanente - Westside Medical Office	Hillsboro	Oregon
United States	Memorial Regional Hospital	Hollywood	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Clearview Cancer Institute (CCI)	Huntsville	Alabama
United States	Indiana University - Melvin and Bren Simon Cancer	Indianapolis	Indiana
United States	Jackson Oncology Associates	Jackson	Mississippi
United States	Cancer Specialists of North Florida	Jacksonville	Florida
United States	Mayo Clinic Cancer Center	Jacksonville	Florida
United States	HCA Midwest Division (Kansas City)	Kansas City	Missouri
United States	Saint Luke's Hospital	Kansas City	Missouri
United States	University of Tennessee Medical Center	Knoxville	Tennessee
United States	Clinical Research Alliance	Lake Success	New York
United States	Cancer Center of Southwest Oklahoma	Lawton	Oklahoma
United States	Los Angeles Hematology Oncology Medical Group	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Bon Secours Cancer Institute Medical Oncology	Midlothian	Virginia
United States	Aurora St. Luke's Medical Center - Vince Lombardi	Milwaukee	Wisconsin
United States	West Virginia University Mary Babb Randolph Cancer Center (MBRCC)	Morgantown	West Virginia
United States	SCRI - Tennessee Oncology	Nashville	Tennessee
United States	Weill Cornell Medicine/ NewYork-Presbyterian	New York	New York
United States	Helen F. Graham Cancer Center	Newark	Delaware
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	Mercy Clinic Oncology and Hematology - McAuley	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	St. Joseph Hospital of Orange	Orange	California
United States	UF Health Cancer Center - Orlando Health	Orlando	Florida
United States	Fox Chase Cancer Center (FCCC) - Philadelphia	Philadelphia	Pennsylvania
United States	Mayo Clinic	Phoenix	Arizona
United States	FirstHealth Outpatient Cancer Center	Pinehurst	North Carolina
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	OHSU Knight Cancer Institute	Portland	Oregon
United States	Torrance Health Association DBA Torrance Memorial	Redondo Beach	California
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Oncology and Hematology Associates of Southwest Virginia	Roanoke	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York
United States	UC Davis	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro MN Clinical Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Florida Cancer Specialists North	Saint Petersburg	Florida
United States	UCLA Medical Center Santa Monica Hematology And Oncology	Santa Monica	California
United States	Maine Center for Cancer Medicine - Scarborough	Scarborough	Maine
United States	Avera Medical Group	Sioux Falls	South Dakota
United States	Mercy Clinic - Cancer & Hematology	Springfield	Missouri
United States	Stony Brook University	Stony Brook	New York
United States	MultiCare Institute for Research and Innovation	Tacoma	Washington
United States	Toledo Clinic Cancer Centers	Toledo	Ohio
United States	Cotton O'Neil Cancer Center	Topeka	Kansas
United States	Carle Cancer Center CCOP	Urbana	Illinois
United States	Kaiser Permanente - Vallejo Medical Center	Vallejo	California
United States	Northwestern Medicine Regional Medical Group	Warrenville	Illinois
United States	Georgetown University Medical Center (GUMC)	Washington	District of Columbia
United States	Florida Cancer Specialists East Region	Wellington	Florida
United States	Cancer Center of Kansas	Wichita	Kansas
United States	Wake Forest Baptist Hospital	Winston-Salem	North Carolina
United States	UMass Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Sumitomo Pharma America, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  China,  Czechia,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Portugal,  Russian Federation,  Singapore,  Spain,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall Survival in Biomarker Positive Patients	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 in biomarker positive patients. This biomarker-positive sub-population is defined as those patients with phospho-STAT3 positivity based on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.	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.
Other	Progression Free Survival in Biomarker Positive Patients	To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Progression Free Survival (PFS) of patients with metastatic pancreatic ductal adenocarcinoma in biomarker positive patients. PFS is defined as the time from randomization to the first objective documentation of disease progression or death due to any cause. This biomarker-positive sub-population is defined as those patients with phospho-STAT3 positivity based on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.	From date of randomization, every 8 weeks, until the date of first documented objective disease progression, up to 36 months
Other	Disease Control Rate in Biomarker Positive Patients	To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Disease Control Rate (DCR) of patients with metastatic pancreatic ductal adenocarcinoma in biomarker positive patients. DCR is evaluated using RECIST 1.1. This biomarker-positive sub-population is defined as those patients with phospho-STAT3 positivity based on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.	From date of randomization, every 8 weeks, until the date of first documented objective disease progression, up to 36 months
Other	Overall Response Rate in Biomarker Positive Patients	To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Overall Response Rate (ORR) of patients with metastatic pancreatic ductal adenocarcinoma in biomarker positive patients. ORR is evaluated using RECIST 1.1. This biomarker-positive sub-population is defined as those patients with phospho-STAT3 positivity based on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.	From date of randomization, every 8 weeks, until the date of first documented objective disease progression, up to 36 months
Primary	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.	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.
Secondary	Progression Free Survival	To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Progression Free Survival (PFS) of patients with metastatic pancreatic ductal adenocarcinoma. PFS is defined as the time from randomization to the first objective documentation of disease progression or death due to any cause.	From date of randomization, every 8 weeks, until the date of first documented objective disease progression, up to 36 months
Secondary	Disease Control Rate	To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Disease Control Rate (DCR) of patients with metastatic pancreatic ductal adenocarcinoma. DCR is defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.	From date of randomization, every 8 weeks, until the date of first documented objective disease progression, up to 36 months
Secondary	Overall Response Rate	To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Overall Response Rate (ORR) of patients with metastatic pancreatic ductal adenocarcinoma. ORR is evaluated using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1).	From date of randomization, every 8 weeks, until the date of first documented objective disease progression, up to 36 months
Secondary	Number of Patients With Adverse Events	All patients who have received at least one dose of napabucasin will be included in the safety analysis according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.0. The incidence of adverse events will be summarized by type of adverse event and severity.	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.
Secondary	Mean Change From Baseline for Global Quality of Life (QoL) at 8 Weeks.	QoL will be measured using the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ-C30) in patients with metastatic pancreatic ductal adenocarcinoma with napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine. EORTQ QLC-C30 is a questionnaire used to assess the overall quality of life in cancer patients - 28 questions use a 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions use a 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged and transformed to 0-100 scale; higher overall score = better quality of life.	8 weeks