A Study of PEGylated Recombinant Human Hyaluronidase in Combination With Nab-Paclitaxel Plus Gemcitabine Compared With Placebo Plus Nab-Paclitaxel and Gemcitabine in Participants With Hyaluronan-High Stage IV Previously Untreated Pancreatic Ductal Adenocarcinoma

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) in Combination With Nab-Paclitaxel Plus Gemcitabine Compared With Placebo Plus Nab-Paclitaxel and Gemcitabine in Subjects With Hyaluronan-High Stage IV Previously Untreated Pancreatic Ductal Adenocarcinoma

The purpose of this study is to compare the efficacy and safety of PEGylated Recombinant Human Hyaluronidase (PEGPH20) combined with nab-paclitaxel plus gemcitabine (PAG treatment), compared with placebo combined with nab-paclitaxel plus gemcitabine (AG treatment), in participants with hyaluronan (HA)-high Stage IV previously untreated pancreatic ductal adenocarcinoma (PDA).

Study Overview

• Status: Terminated
• Conditions: Pancreatic Ductal Carcinoma
• Intervention / Treatment: Other: Biological: PEGylated Recombinant Human Hyaluronidase (PEGPH20); Drug: nab-Paclitaxel; Drug: Gemcitabine; Drug: Placebo

Detailed Description

Participants will be randomized in a 2:1 ratio to PAG or AG treatment.

• Study Type: Interventional
• Enrollment (Actual): 492
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Bankstown, New South Wales, Australia
      • Bankstown-Lidcombe Hospital
    • Camperdown, New South Wales, Australia
      • Chris O'Brien Lifehouse
    • Darlinghurst, New South Wales, Australia
      • St Vincent's Hospital
    • St Leonards, New South Wales, Australia
      • Royal North Shore Hospital
  • South Australia
    • Bedford, South Australia, Australia
      • Flinders Medical Centre
  • Victoria
    • Bendigo, Victoria, Australia
      • Bendigo Health Care Group
    • Bentleigh East, Victoria, Australia
      • Monash Health
    • Frankston, Victoria, Australia
      • Peninsula & South Eastern Haematology and Oncology Group
• Belgium
  • Liege, Belgium
    • Centre Hospitalier Universitaire (CHU) de Liege - Domaine Un
  • Antwerpen
    • Bonheiden, Antwerpen, Belgium
      • Imelda Ziekenhuis
    • Edegem, Antwerpen, Belgium
      • UZA
  • Brussels Capital Region
    • Brussels, Brussels Capital Region, Belgium, 1200
      • Cliniques Universitaires Saint-Luc
    • Bruxelles, Brussels Capital Region, Belgium
      • Hôpital Erasme
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium
      • Az Maria Middelares - Campus Maria Middelares
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium
      • UZ Leuven - Campus Gasthuisberg
• Brazil
  • Barretos, Brazil
    • Fundacao Pio Xii Hospital de Cancer de Barretos
  • Rio de Janeiro, Brazil
    • Instituto COI
  • Rio de Janeiro, Brazil
    • Instituto Nacional de Câncer - INCA
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil
      • Cenantron - Centro Avancado de Tratamento Oncologico
  • Rio Grande Do Sul
    • Passo Fundo, Rio Grande Do Sul, Brazil
      • Hospital da Cidade de Passo Fundo
    • Porto Alegre, Rio Grande Do Sul, Brazil
      • Hospital São Lucas da PUCRS
    • Porto Alegre, Rio Grande Do Sul, Brazil
      • Hospital de Clinicas de Porto Alegre - UFRGS
  • São Paulo
    • Campinas, São Paulo, Brazil
      • Occ -Oncologia Clínica De Campinas
    • Jaú, São Paulo, Brazil
      • Fundação Amaral Cravalho / Hospital Amaral Carvalho
    • Santo Andre, São Paulo, Brazil
      • Fm Abc/ Cepho
    • Sao Paulo, São Paulo, Brazil
      • Faculdade de Medicina da Universidade de Sao Paulo
• Canada
  • Ontario
    • Barrie, Ontario, Canada
      • Royal Victoria Regional Health Centre
    • Toronto, Ontario, Canada
      • Princess Margaret Hospital
• Croatia
  • Zagreb, Croatia
    • Klinički bolnički centar Sestre Milosrdnice
  • Grad Zagreb
    • Zagreb, Grad Zagreb, Croatia
      • Klinički bolnički centar Zagreb
• Czechia
  • Prague, Czechia
    • Nemocnice Na Bulovce (Hospital Na Bulovce)
  • Praha 5, Czechia
    • Fakultni Nemocnice V Motole
  • Brno-město
    • Brno, Brno-město, Czechia
      • Masarykuv onkologicky ustav
  • Královéhradecký Kraj
    • Hradec Kralove, Královéhradecký Kraj, Czechia
      • FN Hradec Kralove
  • Olomoucký Kraj
    • Olomouc, Olomoucký Kraj, Czechia
      • Fakultni Nemocnice Olomouc
• Denmark
  • South Denmark
    • Odense, South Denmark, Denmark
      • Odense Universitetshospital
• Estonia
  • Harjumaa
    • Tallinn, Harjumaa, Estonia
      • East Tallinn Central Hospital Oncology Center
    • Tallinn, Harjumaa, Estonia
      • North Estonian Medical Centre Foundation Clinic of Oncology
• France
  • Angers Cedex 02, France
    • Institut de cancérologie de l'Ouest - Site Paul Papin
  • Bordeaux, France
    • Hôpital Haut-Lévêque
  • Créteil, France
    • Henri Mondor - Albert Chevenier
  • Lyon, France
    • Hopital Prive Jean Mermoz
  • Lyon Cedex, France
    • Centre Lyon Berard
  • Paris, France
    • Institut Mutualiste Montsouris
  • Paris, France
    • Pitié Salpétrière Hospital
  • Bretagne
    • Rennes Cedex, Bretagne, France
      • Centre Eugène Marquis
  • Franche-Comté
    • Besançon cedex, Franche-Comté, France
      • Hospitalier Jean Minjoz
  • Hérault
    • Montpellier, Hérault, France
      • ICM Val d'Aurelle Saint Eloi - Departement Oncologie
  • Loire-Atlantique
    • Saint Herblain, Loire-Atlantique, France
      • ICO - Site Ren Gauducheau
  • Puy-de-Dôme
    • Clermont-Ferrand, Puy-de-Dôme, France
      • Chu Estaing
  • Rhône
    • Lyon Cedex 03, Rhône, France
      • Hôpital Edouard Herriot
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France
      • Institut de Cancerologie Gustave Roussy
  • Île-de-France
    • Clichy Cedex, Île-de-France, France
      • Hopital Beaujon
• Germany
  • Berlin, Germany
    • Charité - Universitätsmedizin Berlin
  • Essen, Germany
    • Kliniken Essen-Mitte Evang. Huyssens-Stiftung
  • Halle, Germany
    • Universitätsklinikum Halle-Universitätsklinik und Poliklinik
  • Hamburg, Germany
    • Facharztzentrum Eppendorf
  • Heidelberg, Germany
    • Universitätskllinikum Heidelberg
  • Baden-Württemberg
    • Ulm, Baden-Württemberg, Germany
      • Universitätsklinikum Ulm
  • Bayern
    • München, Bayern, Germany
      • Klinikum der Universität München - Campus Großhadern
  • Nordrhein-Westfalen
    • Bonn, Nordrhein-Westfalen, Germany
      • Universitätsklinikum Bonn
    • Koeln, Nordrhein-Westfalen, Germany
      • Uniklinik Köln-Klinik für Gastroenterologie und Hepatologie am Abdominalzentrum
  • Sachsen
    • Dresden, Sachsen, Germany
      • Universitätsklinik Carl-Gustav-Carus Dresden
    • Leipzig, Sachsen, Germany
      • Universitätsklinikum Leipzig AöR
• Hungary
  • Budapest, Hungary
    • Egyesített Szent István és Szent László Kórház-Rendelőintéze
  • Budapest, Hungary
    • Magyar Honvedseg Egeszsegugyi Kozpont
  • Budapest, Hungary
    • Orszagos Onkologiai Intezet
  • Budapest, Hungary
    • Semmelweis Egyetem - Isz. Bel, Onkológiai Részleg
  • Budapest, Hungary
    • Semmelweis Egyetem - Onkohaematológiai Osztály
  • Budapest, Hungary
    • Szent Margit Kórház
  • Kaposvár, Hungary
    • Somogy Megyei Kaposi Mór Oktató Kórház
  • Baranya
    • Pécs, Baranya, Hungary
      • Pecsi Tudomanyegyetem Klinikai Kozpont
  • Csongrád
    • Szeged, Csongrád, Hungary
      • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpo
  • Gyor-Moson-Sopron
    • Győr, Gyor-Moson-Sopron, Hungary
      • Petz Aladár Megyei Oktató Kórház
  • Hajdú-Bihar
    • Debrecen, Hajdú-Bihar, Hungary
      • Debreceni Egyetem Klinikai Kozpont
• Israel
  • Afula, Israel
    • Ha'Emek Medical Center
  • Beer Sheva, Israel
    • Soroka Medical Center [Oncology]
  • Hadera, Israel
    • Hillel Yaffe Medical Center
  • Haifa, Israel
    • Rambam Health Care Campus
  • Jerusalem, Israel
    • Shaare Zedek Medical Center
  • Tel Hashomer, Israel
    • The Chaim Sheba Medical Center [Oncology]
  • HaMerkaz
    • Be'er Ya'aqov, HaMerkaz, Israel
      • Assaf Harofeh Medical Center
    • Kfar-Saba, HaMerkaz, Israel
      • Meir Medical Center
    • Petah Tikva, HaMerkaz, Israel
      • Rabin Medical Center - Beilinson Hospital
  • Tel-Aviv
    • Tel Aviv, Tel-Aviv, Israel
      • Tel Aviv Sourasky Medical Center
  • Yerushalayim
    • Jerusalem, Yerushalayim, Israel
      • Hadassah Medical Organisation
• Italy
  • Cremona, Italy
    • PO di Cremona, ASST di Cremona
  • Genova, Italy
    • AO S. Martino, IRCCS, IST-Istituto Nazionale Ricerca Sul Cancro
  • Milan, Italy
    • Ieo, Irccs
  • Milano, Italy
    • IRCCS Ospedale S.Raffaele
  • Padova, Italy
    • Istituto Oncologico Veneto IOV-IRCCS
  • Roma, Italy
    • Regina Elena, Istituto Nazionale Dei Tumori, Ifo, Irccs
  • Verona, Italy
    • Borgo Roma, Policlinico G.Rossi, AOU Integrata Verona
  • Foggia
    • San Giovanni Rotondo, Foggia, Italy
      • U.O. di Oncologia
  • Milano
    • Rozzano, Milano, Italy
      • Istituto Clinico Humanitas Rozzano, IRCCS
• Korea, Republic of
  • Incheon, Korea, Republic of
    • Gachon University Gil Medical Center
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Korea University Guro Hospital
  • Busan Gwang'yeogsi
    • Busan, Busan Gwang'yeogsi, Korea, Republic of
      • Dong-A University Hospital
  • Daegu Gwang'yeogsi
    • Daegu, Daegu Gwang'yeogsi, Korea, Republic of
      • Keimyung University Dongsan Medical Center
  • Gyeonggido
    • Seongnam, Gyeonggido, Korea, Republic of
      • Seoul National University Bundang Hospital
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of
      • Asan Medical Center
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of
      • Korea University Anam Hospital
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of
      • Samsung Medical Center
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of
      • Severance Hospital, Yonsei University Health System
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of
      • The Catholic University of Korea, Seoul St.Mary's Hospital
• Latvia
  • Daugavpils, Latvia
    • Daugavpils Regional Hospital
  • Riga, Latvia
    • P.Stradins Clinical University
  • Riga, Latvia
    • SIA "Rigas Austrumu Kliniska Universitates Slimnica"
• Lithuania
  • Vilniaus Apskritis
    • Vilnius, Vilniaus Apskritis, Lithuania
      • National Cancer Institute
    • Vilnius, Vilniaus Apskritis, Lithuania
      • Vilniaus Universiteto ligonines Santariskiu Klinikos
• Netherlands
  • Amsterdam, Netherlands
    • Academisch Medisch Centrum Universiteit van Amsterdam
  • Hoofddorp, Netherlands
    • Spaarne Gasthuis
  • Nijmegen, Netherlands
    • Radboud Universiteit Nijmegen
  • Limburg
    • Maastricht, Limburg, Netherlands
      • Maastricht University Medical Centre
• Poland
  • Lublin, Poland
    • Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
  • Warszawa, Poland
    • Centrum Onkologii Instytut im. M. Sklodowskiej-Curie
  • Podkarpackie
    • Brzozow, Podkarpackie, Poland
      • Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onko
• Spain
  • Barcelona, Spain
    • H.del Mar
  • Barcelona, Spain
    • H.Sta.Creu i St.Pau
  • Barcelona, Spain
    • H.U.Vall d'Hebrón
  • Madrid, Spain
    • H.C. S.Carlos
  • Madrid, Spain
    • H.G.U. G. Marañón
  • Madrid, Spain
    • H.U. F. Jiménez Díaz
  • Madrid, Spain
    • H.U. R. y Cajal
  • Madrid, Spain
    • Hospital Madrid Norte Sanchinarro
  • Valencia, Spain
    • Hospital Universitari i Politecnic La Fe
  • Valencia, Spain
    • F.I. Valenciano de Oncología
  • Zaragoza, Spain
    • H.U. Miguel Servet
  • Barcelona
    • Badalona, Barcelona, Spain
      • Institut català d'oncologia-hospital germans trias i pujol
    • L'Hospitalet De Llobregat, Barcelona, Spain
      • Institut Catalá d´Oncología (I.C.O.)
  • Madrid
    • Fuenlabrada, Madrid, Spain
      • H.U. de Fuenlabrada
  • Navarra
    • Pamplona, Navarra, Spain
      • Clinica Universidad de Navarra
• Taiwan
  • Changhua, Taiwan
    • Changhua Christian Hospital
  • Tainan, Taiwan
    • National Cheng Kung University Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Veterans General Hospital- Taipei
  • Taichung Municipality
    • Taichung, Taichung Municipality, Taiwan
      • China Medical University Hospital
• United Kingdom
  • Birmingham, United Kingdom
    • Queen Elizabeth Hospital Birmingham
  • Cottingham, United Kingdom
    • Castle Hill Hospital
  • Coventry, United Kingdom
    • Coventry Hospital
  • London, United Kingdom
    • Hammersmith Hospital
  • London, United Kingdom
    • The Royal Marsden NHS Foundation - Sutton
  • London, United Kingdom
    • The Royal Marsden Nhs Foundation Trust - Chelsea
  • Rhyl, United Kingdom
    • North Wales Cancer Treatment Centre
  • Wirral, United Kingdom
    • The Clatterbridge Cancer Centre NHS Foundation Trust
  • Withington, United Kingdom
    • The Christie NHS Foundation Trust
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom
      • Addenbrooke's Hospital, Cambridge
    • Peterborough, Cambridgeshire, United Kingdom
      • Peterborough And Stamford Hospitals
  • Glasgow City
    • Glasgow, Glasgow City, United Kingdom
      • Beatson West of Scotland Cancer Centre
  • London, City Of
    • London, London, City Of, United Kingdom
      • Sarah Cannon Research Institute UK (SCRI UK)
  • Midlothian
    • Edinburgh, Midlothian, United Kingdom
      • Edinburgh Cancer Centre Western General Hospital
  • Wirral
    • Birkenhead, Wirral, United Kingdom
      • The Clatterbridge Cancer Centre NHS Foundation Trust
• United States
  • Alabama
    • Mobile, Alabama, United States, 36604
      • University of South Alabama
  • Arizona
    • Gilbert, Arizona, United States, 85234-2165
      • Banner MD Anderson Cancer Center
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
  • California
    • Fullerton, California, United States, 92886
      • St. Jude Hospital Yorba DBA Linda St. Joseph Heritage Health
    • La Jolla, California, United States, 92037
      • Scripps Clinical Research Services
    • Los Angeles, California, United States, 90048
      • Samuel Oschin Comprehensive Cancer Institute
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicine (DGSOM) at UCLA
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center
    • Orange, California, United States, 92868
      • St. Joseph Hospital
    • Rancho Mirage, California, United States, 92270
      • Desert Hematology Oncology Medical Group, Inc.
    • Redondo Beach, California, United States, 90277
      • Cancer Care Associates Medical Group, Inc.
    • San Francisco, California, United States, 94115
      • UCSF Helen Diller Family Comprehensive Cancer Center
    • San Francisco, California, United States, 94115
      • Pacific Hematology Oncology Associates
    • San Luis Obispo, California, United States, 93401
      • Pacific Central Coast Health Centers: San Luis Obispo Oncology and Hematology Health Center
    • Santa Rosa, California, United States, 95405
      • St Joseph Heritage Healthcare
    • Whittier, California, United States, 90603
      • Innovative Clinical Research Institution
  • Colorado
    • Denver, Colorado, United States, 80205
      • Kaiser Permanente Franklin Medical Offices - Denver
    • Denver, Colorado, United States, 80218
      • US Oncology - Rocky Mountain Cancer Centers - Midtown
    • Grand Junction, Colorado, United States, 81501
      • St. Mary's Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Healthcare System - Memorial Cancer Institute
    • Jacksonville, Florida, United States, 32207
      • 21st Century Oncology
    • Orlando, Florida, United States, 32806
      • MD Anderson Cancer Center Orlando
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Fort Wayne Medical Oncology/Hematology, INC.
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40292
      • University of Louisville
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Ochsner Health Center
    • New Orleans, Louisiana, United States, 70119
      • Ochsner Clinic CCOP
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • The Sidney Kimmel Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Worcester, Massachusetts, United States, 01605
      • UMass Memorial Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical School
    • Minneapolis, Minnesota, United States, 55404
      • Virginia Piper Cancer Institute
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03743
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Clifton, New Jersey, United States, 07013
      • Saint Joseph's Ambulatory Clinic
    • Neptune, New Jersey, United States, 07753
      • Jersey Shore University Medical Center
  • New York
    • Lake Success, New York, United States, 11042
      • Northwell Health/Monter Cancer Center
    • New Hyde Park, New York, United States, 10016
      • NYU Langone Medical Center - NYU Langone Arena Oncology
    • New York, New York, United States, 10019
      • Columbia University Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine - The Tisch Cancer Institute
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Rex Cancer Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • The University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • Univ of Pittsburgh Cancer institute
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine - Baylor Clinic
    • Temple, Texas, United States, 76508
      • Scott and White
  • Utah
    • Salt Lake City, Utah, United States, 84103
      • University of Utah - Huntsman Cancer Institute
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Dwight and Martha Schar Cancer Institute
    • Fort Belvoir, Virginia, United States, 22060
      • Fort Belvoir Community Hospital
    • Mechanicsville, Virginia, United States, 23116
      • Virginia Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute/ Swedish Health Services
    • Seattle, Washington, United States, 98195
      • University of Washington (UW) - Seattle Cancer Care Alliance
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties PLLC
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Health - UW Carbone Cancer Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53211
      • Columbia St. Marys

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

Participants must satisfy all the following inclusion criteria to be enrolled in the study:

1. Signed, written Institutional Review Board/Ethics Committee-approved Informed Consent Form (ICF).
2. Stage IV PDA with histological or cytological confirmation of PDA.

3. Participants must be determined to be HA-high based on archived or fresh tumor core biopsy or sample obtained after the participant has documented metastatic disease. Biopsies/samples must meet the following requirements:

   1. Pancreas tumor biopsies/samples obtained on or after the date that metastatic disease is documented or tumor biopsies/samples from a metastatic lesion are acceptable.
   2. Tumor biopsies or samples must meet the requirements provided in the Study Laboratory Manual with regard to tumor tissue architecture. Note: cytology samples from fine needle aspirates without maintained tissue architecture or brushing biopsies are not acceptable.
   3. Tumor tissue (formalin-fixed paraffin-embedded [FFPE] block preferred) must include enough tumor to make a minimum of 5-10 unstained, consecutive FFPE slides (10 slides are preferred) of 1 archival block that meet specific tissue sample requirements.
4. Radiographic confirmation of Stage IV PDA with at least 1 tumor metastasis measurable on computed tomography (CT) scan or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, excluding the primary pancreatic lesion.
5. If a participant has had adjuvant/neoadjuvant therapy and/or therapy for locally advanced disease (chemotherapy for non-metastatic pancreatic cancer in combination with or without radiation therapy), tumor recurrence or disease progression must have occurred no sooner than 6 months after completing the last dose of the aforementioned therapies, provided all toxicities have returned to baseline or less than or equal to (≤) Grade 1.
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
7. Life expectancy greater than or equal to (≥) 3 months.
8. Age ≥18 years.
9. A negative urine or serum pregnancy test within 7 days before Cycle 1, Day 1 (C1D1; first dose of study medication) if female participant is of childbearing potential.

10. Screening clinical laboratory values as follows:

    1. Total bilirubin ≤1.5 times upper limit of normal (ULN) (participants with Gilbert syndrome are eligible independent of bilirubin levels).
    2. Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvate transaminase) ≤2.5 times ULN, (if liver metastases are present, then ≤5 times ULN is allowed).
    3. Serum creatinine ≤2.0 milligrams/deciliter (mg/dL) or calculated creatinine clearance ≥40 milliliters/minute (mL/min).
    4. Serum albumin ≥2.5 grams/deciliter (g/dL).
    5. Prothrombin time or international normalized ratio (INR) within normal limits (±15%), unless participant takes warfarin, in which case prothrombin time or INR result must be within therapeutic range.
    6. Partial thromboplastin time (PTT) within normal limits (±15%).
    7. Hemoglobin ≥9 g/dL (transfusion and erythropoietic agents allowed).
    8. Absolute neutrophil count ≥1,500 cells/cubic millimeter (cells/mm^3).
    9. Platelet count ≥100,000/mm^3.
11. For women of childbearing potential (WOCBP) and for men, agreement to use a highly effective contraceptive method from the time of screening throughout the study until 1 month (WOCBP) or 6 months (men) after administration of the last dose of any study medication. Highly effective contraceptive methods consist of prior sterilization, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), oral or injectable contraceptives, barrier methods, and/or true sexual abstinence.

Exclusion criteria:

Participants are ineligible for enrollment if they meet any of the following exclusion criteria:

1. Clinical evidence of deep vein thrombosis (DVT), pulmonary embolism (PE) or other known thromboembolic (TE) event present during the screening period.

   1. Participants with superficial vein thrombosis are eligible.
   2. Participants with visceral/splanchnic vein thrombosis are still eligible if, in the opinion of the Investigator, the visceral/splanchnic vein thrombosis is primarily associated with the anatomic location of the underlying disease of metastatic pancreatic cancer (there must be primary or metastatic disease in reasonable proximity to the thrombosis, and the Investigator determines that the thrombosis is due to a local tumor event and not a coagulation issue).

2. Previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease.

   a. Palliative radiotherapy for pain control of metastatic bone lesions is allowed.

3. Known central nervous system involvement or brain metastases.
4. New York Heart Association Class III or IV cardiac disease or myocardial infarction within the past 12 months.
5. History of cerebrovascular accident or transient ischemic attack.
6. Clinically significant pre-existing carotid artery disease.
7. Known infection with human immunodeficiency virus, or active infection with hepatitis B or hepatitis C within the past 12 months.
8. Known allergy to hyaluronidase.
9. Current use of megestrol acetate or megestrol acetate-containing drugs (use within 10 days of Day 1).
10. Contraindication to heparin as per institutional guidelines.
11. Women currently pregnant or breastfeeding.
12. Intolerance to dexamethasone.
13. History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical carcinoma in-situ.
14. Any other disease, active, uncontrolled bacterial, viral or fungal infection requiring systemic therapy, metabolic dysfunction, physical examination finding or clinical laboratory finding that leads to reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, or that may affect the interpretation of the results, or that may render the participant at high risk for treatment complications.
15. Immunization with a live vaccine up to 2 weeks prior to Day 1.
16. Hypersensitivity to the active substance or ingredients of PEGPH20, gemcitabine, and nab-paclitaxel.
17. Inability to comply with study and follow-up procedures as judged by the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PAG: PEGPH20 + nab-Paclitaxel + Gemcitabine; Participants will receive 3.0 micrograms/kilogram (μg/kg) PEGPH20 as an intravenous (IV) infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks [Week 4 of every cycle will be a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 milligrams/square meter (mg/m^2) nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment will continue until disease progression, unacceptable toxicity, death, or withdrawal of consent.	Other: Biological: PEGylated Recombinant Human Hyaluronidase (PEGPH20); PEGPH20 will be administered as per the dose and schedule specified in the respective arms.; Drug: nab-Paclitaxel; Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.; Other Names: Abraxane®; Drug: Gemcitabine; Gemcitabine will be administered as per the dose and schedule specified in the respective arms.; Other Names: Gemzar®
Placebo Comparator: AG: Placebo + nab-Paclitaxel + Gemcitabine; Participants will receive placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks [Week 4 of every cycle will be a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment will continue until disease progression, unacceptable toxicity, death, or withdrawal of consent.	Drug: nab-Paclitaxel; Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.; Other Names: Abraxane®; Drug: Gemcitabine; Gemcitabine will be administered as per the dose and schedule specified in the respective arms.; Other Names: Gemzar®; Drug: Placebo; Matching placebo for PEGPH20

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival was defined as the time from randomization until death from any cause. Overall survival was analyzed using Kaplan-Meier methods.	From randomization until death from any cause (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS was defined as the time from randomization until the first occurrence of radiological disease progression, as determined by the blinded Central Imaging Vendor (CIV) based on Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, or death from any cause during the treatment period. Disease progression was defined as at least a 20 percent (%) increase in sum of diameters of target lesions, taking as reference the smallest sum on study thus far, nadir (this included baseline sum if that was the smallest on study); Sum must also demonstrate an absolute increase of at least 5 millimeters (mm); Appearance of one or more new lesions; Unequivocal progression of existing non-target lesions. Surviving participants without disease progression were censored for PFS analysis at the date of last evaluable post-baseline tumor assessment. Surviving participants without any post-baseline disease assessment were censored on Day 1. PFS was estimated using Kaplan-Meier method.	From the date of randomization until disease progression or death from any cause (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)
Objective Response Rate (ORR): Percentage of Participants With Objective Response	ORR was defined as percentage of participants who achieved either a complete response (CR) or partial response (PR) as determined by the blinded CIV based on RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions; Any pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From the date of randomization until CR or PR (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)
Duration of Response (DOR)	DOR was defined as the time from the first objective response of CR or PR until disease progression (as determined by the blinded CIV based on RECIST version 1.1) or death within 14 days of last dose of study treatment or randomization. CR was defined as disappearance of all target and non-target lesions; Any pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study thus far, the sum must also demonstrate an absolute increase of at least 5 mm, or the appearance of one or more new lesions; and unequivocal progression of existing non-target lesions. DOR was analyzed using Kaplan-Meier methods.	From date of first objective response (CR or PR) until date of first disease progression (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)
Number of Participants With Treatment-Emergent Adverse Events (AEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were defined as AEs that begin or worsen in severity during or after the participant's first dose of study treatment and no later than 30 days after the date of the last dose of study treatment and/or any treatment-related AE regardless of the onset date. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.	From administration of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)
Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study	Severity grade associated with a laboratory parameter value was determined using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening. Grade 0 indicates evaluable lab records but not fall into any CTCAE grade for certain CTCAE term. A worst post-baseline grade shift was defined as the worst change that occurred at any measured timepoint during study. Hematology abnormalities: anemia(hemoglobin decreased), lymphocyte count decreased, lymphocyte count increased, neutropenia(neutrophil count decreased), thrombocytopenia(platelet count decreased), and leukopenia(white blood cell decreased). Chemistry abnormalities: hypoalbuminemia, alkaline phosphatase increased, alanine aminotransferase increased, aspartate aminotransferase increased, hyperbilirubinemia, hypo- and hypercalcemia, creatinine increased, hypo- and hyperglycaemia, hypo- and hyperkalemia, hypo- and hypermagnesemia, hypo- and hypernatremia.	From administration of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)	ECGs including clinical significance was evaluated by the Investigator. Criteria for clinical significance were as per investigator's discretion.	From administration of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)
Number of Participants With Clinically Significant Abnormalities in Vital Signs	Vital signs included measurement of blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]), heart rate, and body weight. Criteria for clinical significance abnormalities were: Heart rate: <50 beats per minute (bpm), >120 bpm, >=30 bpm increase from baseline, >=30 bpm decrease from baseline. SBP: >140 millimeters of mercury (mmHg) and increase from baseline >20 mmHg, >180 mmHg, <90 mmHg and decrease from baseline >10 mmHg. DBP: >90 mmHg and increase from baseline >20 mmHg, >105 mmHg, <60 mmHg and decrease from baseline >10 mmHg. Change in weight: >=5% increase from baseline, >=5% decrease from baseline.	From administration of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)

Collaborators and Investigators

• Sponsor: Halozyme Therapeutics
• Investigators: Study Director: VP, Medical, Regulatory and Drug Safety, Halozyme Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2016
• Primary Completion (Actual): November 4, 2019
• Study Completion (Actual): November 4, 2019

Study Registration Dates

• First Submitted: March 17, 2016
• First Submitted That Met QC Criteria: March 17, 2016
• First Posted (Estimate): March 22, 2016

Study Record Updates

• Last Update Posted (Actual): July 14, 2020
• Last Update Submitted That Met QC Criteria: June 30, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Gemcitabine; Metastatic; Nab-paclitaxel; Stage IV; Pancreatic ductal adenocarcinoma (PDA); Pancreatic ductal carcinoma; PEGylated Recombinant Human Hyaluronidase (PEGPH20)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Ductal, Lobular, and Medullary; Pancreatic Neoplasms; Adenocarcinoma; Carcinoma, Ductal; Carcinoma, Pancreatic Ductal; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Gemcitabine; Paclitaxel
• Other Study ID Numbers: HALO-109-301; 2015-004068-13 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No