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

Pancreatic Ductal Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02715804
• Other study ID #: HALO-109-301
• Secondary ID: 2015-004068-13
• Status: Terminated
• Phase: Phase 3
• Start date: March 14, 2016
• Est. completion date: November 4, 2019

Study information

• Verified date: June 2020
• Source: Halozyme Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 492
• Est. completion date: November 4, 2019
• Est. primary completion date: November 4, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma, Ductal
• Carcinoma, Pancreatic Ductal
• Pancreatic Ductal Carcinoma

Intervention

Other:
• Biological: PEGylated Recombinant Human Hyaluronidase (PEGPH20)
PEGPH20 will be administered as per the dose and schedule specified in the respective arms.

Drug:
• Placebo
Matching placebo for PEGPH20
• nab-Paclitaxel
Nab-paclitaxel will be administered as per the dose and schedule specified in the respective arms.
• Gemcitabine
Gemcitabine will be administered as per the dose and schedule specified in the respective arms.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Halozyme Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Croatia,  Czechia,  Denmark,  Estonia,  France,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  Latvia,  Lithuania,  Netherlands,  Poland,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)