A Phase 3 Randomized, Placebo-controlled Trial of Carboplatin and Paclitaxel With or Without Veliparib (ABT-888) in HER2-negative Metastatic or Locally Advanced Unresectable BRCA-associated Breast Cancer

Metastatic Breast Cancer Clinical Trial

Official title:

A Phase 3 Randomized, Placebo-Controlled Trial of Carboplatin and Paclitaxel With or Without the PARP Inhibitor Veliparib (ABT-888) in HER2-Negative Metastatic or Locally Advanced Unresectable BRCA-Associated Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02163694
• Other study ID #: M12-914
• Secondary ID: 2014-000345-70
• Status: Completed
• Phase: Phase 3
• Start date: July 17, 2014
• Est. completion date: January 25, 2024

Study information

• Verified date: February 2023
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to assess the progression-free survival (PFS) of veliparib in combination with carboplatin and paclitaxel (C/P) compared to placebo plus C/P in participants with a Breast Cancer Gene 1 or 2 (BRCA1; BRCA2) mutation in Human Epidermal Growth Factor Receptor 2 (HER2)-negative metastatic or locally advanced unresectable breast cancer. The secondary objectives of the study are to assess overall survival (OS), clinical benefit rate (CBR) through the end of Week 24, objective response rate (ORR) and PFS on subsequent therapy (PFS2) in participants treated with veliparib in combination with C/P versus placebo in combination with C/P.

Description:

This is a Phase 3, randomized, double-blind, multinational, multicenter study to evaluate the efficacy and tolerability of veliparib in combination with C/P compared to placebo in combination with C/P in participants with a BRCA1 or BRCA2 mutation, as documented by the Sponsor core laboratory, with HER2-negative metastatic or locally advanced unresectable breast cancer who received no more than 2 prior lines of cytotoxic therapy for metastatic disease. For the purposes of eligibility, HER2-negative status was based on the most recent tumor biopsy. Participants were randomized in a 2:1 ratio, with a total of approximately 500 participants planned to be randomized. Veliparib 120 mg/placebo twice a day (BID) was dosed Days -2 through 5 with carboplatin target area under the concentration-time curve (AUC) 6 administered on Day 1 and paclitaxel 80 mg/m2 administered weekly on Days 1, 8, and 15 of each 21-day cycle. Safety and efficacy data through the prespecified primary analysis cutoff date of 05 April 2019 are included in the interim analysis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 509
• Est. completion date: January 25, 2024
• Est. primary completion date: April 5, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically or cytologically confirmed breast cancer that is either locally advanced or metastatic. Locally advanced breast cancer must not be amenable to surgical resection or radiation with curative intent.

2. Suspected deleterious or deleterious Breast Cancer Gene 1 (BRCA1) and/or Breast Cancer Gene 2 (BRCA2) germline mutation.

3. Breast cancer must be Human Epidermal Growth Factor Receptor 2 (HER2)-negative.

4. Measurable or non-measurable (but radiologically evaluable) disease per Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1 on computed tomography (CT) scan (within 28 days of randomization) with at least one lesion outside previously irradiated areas.

5. Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2.

6. Adequate hematologic, renal, and hepatic function (within 28 days of randomization).

Exclusion Criteria:

1. More than two prior lines of cytotoxic chemotherapy (e.g., gemcitabine, doxorubicin, capecitabine) for metastatic disease.

• Regimens received in the adjuvant/neoadjuvant setting or for locally advanced breast cancer within the past 6 months will also be considered toward the maximum of 2 prior lines of therapy. Adjuvant/neoadjuvant chemotherapy for one cancer event will count as one prior line of therapy, if received within the past 6 months.
• Previous treatments with hormonal therapy (tamoxifen, aromatase inhibitors) and signal transduction agents (e.g., erlotinib, gefitinib, everolimus, bevacizumab) are allowed and are not counted towards the prior line of therapy.

2. Progressed or recurred within 12 months of completing platinum therapy or received > 1 prior line of platinum therapy for breast cancer in any setting (adjuvant, neoadjuvant, or metastatic).

3. Prior therapy with Poly(ADP-ribose)-Polymerase (PARP) inhibitors.

4. Prior taxane therapy administered for the treatment of metastatic breast cancer with the below exceptions.

• Prior taxane therapy for metastatic breast cancer is allowed if the patient received = 1 full cycle (i.e., therapy discontinued within 4 weeks for subjects receiving weekly paclitaxel or Abraxane; therapy discontinued within 3 weeks for subjects receiving paclitaxel or docetaxel every 3 weeks) in the absence of progression or if taxane therapy for metastatic disease was > 12 months prior to Cycle 1 Day-2 (C1D-2).
• Use of taxanes as adjuvant therapy or to treat locally advanced disease is permitted, if given more than 6 months prior to C1D-2

5. Known history of allergic reaction to cremophor-paclitaxel, carboplatin, Azo-Colourant Tartrazine (also known as FD&C Yellow 5 or E102), Azo-Colourant Orange Yellow-S (also known as FD&C Yellow 6 or E110) or known contraindications to any study supplied drug.

6. Active CNS metastases or leptomeningeal disease.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Veliparib Placebo
Supplied as 40 mg, 50 mg, or 100 mg capsules for oral administration twice daily (BID) on Days -2 through 5 of a 21-day cycle.
• Veliparib
Supplied as 40 mg, 50 mg, or 100 mg capsules for oral administration twice daily (BID) on Days -2 through 5 of a 21-day cycle.
• Carboplatin
Administered intravenously over approximately 15 to 30 minutes at an area under the curve (AUC) of 6 mg/mL/min immediately following paclitaxel infusion on Day 1 of every cycle. The duration of carboplatin infusion may be lengthened according to institutional guidelines.
• Paclitaxel
Administered by intravenous infusion over approximately 1 hour at a dose of 80 mg/m² of body-surface area (BSA) on Days 1, 8, and 15 of each 21-day cycle. Paclitaxel is to be infused prior to carboplatin on Day 1. Dosing of veliparib/placebo is to be completed before the carboplatin or paclitaxel infusions.

Locations

Country	Name	City	State
Argentina	COIBA Centro de Oncologia e Investigacion de Buenos Aires /ID# 124839	Berazategui	Buenos Aires
Argentina	Centro Oncologico Riojano Integral /ID# 127938	La Rioja
Argentina	Clinica Pergamino /ID# 127158	Pergamino	Buenos Aires
Argentina	Instituto de Oncoloia de Rosario /ID# 127157	Rosario	Santa Fe
Australia	Duplicate_Flinders Centre for Innovation /ID# 127535	Bedford Park	South Australia
Australia	Townsville University Hospital /ID# 126731	Douglas	Queensland
Australia	Royal Hobart Hospital /ID# 124849	Hobart	Tasmania
Australia	St George Hospital /ID# 129416	Kogarah	New South Wales
Australia	Hollywood Private Hospital /ID# 124843	Nedlands	Western Australia
Australia	The Royal Melbourne Hospital /ID# 124846	Parkville	Victoria
Australia	Duplicate_The Prince of Wales Hospital /ID# 124845	Randwick	New South Wales
Australia	Southern Medical Day Care Centre /ID# 124844	Wollongong	New South Wales
Austria	Medizinische Universitaet Graz /ID# 126450	Graz	Steiermark
Austria	Ordensklinikum Linz GmbH Elisabethinen /ID# 126185	Linz	Oberoesterreich
Austria	Landeskrankenhaus Salzburg-Universitätsklinikum der PMU (LKH) /ID# 126449	Salzburg
Austria	Medizinische Universitaet Wien /ID# 126184	Vienna	Wien
Belarus	Bobruysk Interdistrict Onco. /ID# 137729	Bobruisk
Belarus	State Institution Republican Scientific Practical Center of Oncology and Medical /ID# 125223	Minsk
Belarus	Duplicate_Mogilev Reg Clin Oncology Dis /ID# 137728	Mogilev
Belarus	Vitebsk Regional Clinical Oncology Dispensary /ID# 125219	Vitebsk
Belgium	ZNA Middelheim /ID# 124978	Antwerp
Belgium	Duplicate_AZ St-Jan Brugge-Oostende AV /ID# 124975	Brugge	West-Vlaanderen
Belgium	Grand Hôpital de Charleroi /ID# 124981	Charleroi	Hainaut
Belgium	Universitair Ziekenhuis Antwerpen /ID# 124977	Edegem	Antwerpen
Belgium	Universitair Ziekenhuis Leuven /ID# 124980	Leuven	Vlaams-Brabant
Belgium	CHU UCL Namur - Sainte Elisabeth /ID# 124979	Namur
Belgium	UCL Saint-Luc /ID# 124976	Woluwe-Saint-Lambert	Bruxelles-Capitale
Canada	Duplicate_Jewish General Hospital /ID# 124880	Montreal	Quebec
Canada	CHUM - Notre-Dame Hospital /ID# 124879	Montréal	Quebec
Canada	Duplicate_CHUQ-Hospital St. Sacrement /ID# 124881	Quebec City	Quebec
Canada	Duplicate_Sunnybrook Health Sciences Ctr /ID# 124882	Toronto	Ontario
Chile	Instituto Nacional del Cancer /ID# 129343	Santiago
Chile	ICOS - Inst Clinic Oncology /ID# 125236	Temuco
Chile	Hospital Clinico Vina del Mar /ID# 130100	Vina Del Mar	Valparaíso
Chile	Hospital Clinico Vina del Mar /ID# 148502	Vina Del Mar	Valparaíso
Colombia	Administradora del Country_S.A-Clinica Del Country /ID# 125255	Bogota	Cundinamarca
Colombia	Hospital Univ San Ignacio /ID# 126655	Bogota	Cundinamarca
Colombia	Centro Medico Imbanaco de Cali /ID# 126656	Cali
Colombia	Hospital Pablo Tobon Uribe /ID# 126657	Medellín	Antioquia
Colombia	Instituto Medico de Alta Tecnologia Oncomédica S.A /ID# 129211	Monteria	Cordoba
Czechia	Fakultni Nemocnice Brno /ID# 128176	Brno
Czechia	Masarykuv onkologicky ustav /ID# 124886	Brno
Czechia	Duplicate_FN Hradec Kralove /ID# 127080	Hradec Kralove
Czechia	Fakultni nemocnice Olomouc /ID# 124885	Olomouc
Czechia	Vseobecna fakultni nemocnice v Praze /ID# 124887	Praha
Denmark	Rigshospitalet /ID# 124891	Copenhagen Ø	Hovedstaden
Denmark	Sygehus Lillebælt, Vejle /ID# 124892	Vejle	Syddanmark
Estonia	East Tallinn Central Hospital /ID# 126475	Kesklinna Linnaosa	Harjumaa
Finland	Docrates Cancer Center /ID# 124896	Helsinki
Finland	Duplicate_Helsinki Univ Central Hospital /ID# 124897	Helsinki
Finland	Duplicate_Tampere University Hospital /ID# 124898	Tampere
Finland	Vaasa Central Hospital /ID# 132548	Vaasa
France	Institut Paoli-Calmettes /ID# 124903	Marseille	Bouches-du-Rhone
France	Institut Curie /ID# 124902	Paris CEDEX 05	Ile-de-France
France	Institut Curie - site CLCC René Huguenin /ID# 124904	Saint-cloud
France	Institut de Cancérologie de l'Ouest René Gauducheau /ID# 137726	St Herblain CEDEX	Loire-Atlantique
Germany	Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 127180	Dresden
Germany	Universitaetsklinik Heidelberg /ID# 126664	Heidelberg	Baden-Wuerttemberg
Germany	Universitaetsklinikum Koeln /ID# 126905	Köln	Nordrhein-Westfalen
Germany	Klinikum rechts der Isar - Technische Universitaet Muenchen /ID# 125256	Munich
Germany	Sana Klinikum Offenbach /ID# 126733	Offenbach am Main
Germany	Universitaetsklinimum Tuebingen /ID# 129968	Tubingen	Baden-Wuerttemberg
Germany	Universitaetsklinikum Ulm /ID# 135230	Ulm	Baden-Wuerttemberg
Hungary	Semmelweis Egyetem /ID# 132485	Budapest
Hungary	Pecsi Tudomanyegyetem Klinikai Kozpont /ID# 125259	Pecs
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz /ID# 124911	Szolnok
Hungary	Duplicate_Zala Megyei Korhaz /ID# 131341	Zalaegerszeg
Israel	Duplicate_Soroka University Medical Center /ID# 124917	Be'er Sheva
Israel	Assaf Harofeh Medical Center /ID# 124915	Be'Er Ya'Akov
Israel	Rambam Health Care Campus /ID# 124916	Haifa
Israel	Gastroenterology Institute, Division of Medicine /ID# 124919	Jerusalem
Israel	Shaare Zedek Medical Center /ID# 130275	Jerusalem
Israel	The Chaim Sheba Medical Center /ID# 124918	Ramat Gan	Tel-Aviv
Israel	Kaplan Medical Center /ID# 124914	Rehovot
Israel	Tel Aviv Sourasky Medical Center /ID# 130276	Tel Aviv-Yafo	Tel-Aviv
Italy	Centro di Riferimento Oncologico /ID# 126738	Aviano
Italy	IEO -Istituto Europeo di Oncologia /ID# 125260	Milan	Milano
Italy	Ospedale San Raffaele IRCCS /ID# 125261	Milan	Lombardia
Italy	IRCCS Ospedale Sacro Cuore Don Calabria /ID# 125262	Negrar	Verona
Italy	Grande Ospedale Metropolitano Bianchi Melacrino Morelli /ID# 125263	Reggio Calabria
Korea, Republic of	National Cancer Center /ID# 125602	Goyang	Gyeonggido
Korea, Republic of	Asan Medical Center /ID# 125601	Seoul
Korea, Republic of	Korea University Anam Hospital /ID# 128968	Seoul
Korea, Republic of	Samsung Medical Center /ID# 125598	Seoul
Korea, Republic of	Seoul National University Hospital /ID# 125600	Seoul
Korea, Republic of	Yonsei University Health System Severance Hospital /ID# 125599	Seoul	Seoul Teugbyeolsi
Latvia	Pauls Stradins Clinical University Hospital /ID# 125264	Riga
Latvia	Riga East Clinical University Hospital /ID# 125265	Riga
Lithuania	Hospital of Lithuanian University of Health Sciences Kaunas Clinics /ID# 125266	Kaunas
Lithuania	National Cancer Institute /ID# 125267	Vilnius
Mexico	Centro Oncologico de Chihuahua /ID# 128679	Chihuahua
Mexico	Instituto Nacional de Cancerología INCAN /ID# 128676	Ciudad de Mexico
Mexico	Centro de Estudios Clínicos Especializados /ID# 128680	Mérida	Yucatan
Netherlands	Universitair Medisch Centrum Groningen /ID# 129069	Groningen
Netherlands	Maastricht Universitair Medisch Centrum /ID# 129068	Maastricht
Netherlands	Erasmus Medisch Centrum /ID# 124935	Rotterdam	Zuid-Holland
Norway	Haukeland University Hospital /ID# 150177	Bergen	Hordaland
Poland	Centrum Onkologii Lukaszczyka /ID# 124938	Bydgoszcz	Kujawsko-pomorskie
Poland	Wojewodzki Szpital Zespolony /ID# 126998	Elblag	Warminsko-mazurskie
Poland	Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopern /ID# 126999	Lodz	Lodzkie
Poland	MRUK-MED I Spolka z ograniczona odpowiedzialnoscia /ID# 124939	Rzeszow	Podkarpackie
Poland	Wojewodzki Szpital Specjalistyczny /ID# 127258	Wroclaw	Dolnoslaskie
Portugal	Centro Hospitalar Universitário do Algarve, EPE - Hospital Faro /ID# 125298	Faro
Portugal	Centro Hospitalar Universitário de Lisboa Norte, EPE - Hospital de Santa Maria /ID# 125299	Lisboa
Portugal	Unidade Local de Saúde de Matosinhos, EPE /ID# 126511	Matosinhos
Portugal	Centro Hospitalar Universitario de Sao Joao, EPE /ID# 126508	Porto
Portugal	IPO Porto FG, EPE /ID# 125297	Porto
Portugal	Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE /ID# 126510	Vila Nova De Gaia	Porto
Puerto Rico	Ad-Vance Medical Research, LLC /ID# 126043	Ponce
Puerto Rico	San Juan Municipal Hospital /ID# 124695	San Juan
Romania	Duplicate_lnstitutul Oncologic Prof Dr Alexandru Trestioreanu /ID# 124943	Bucharest
Romania	Spitalul Clinic Judetean de Urgenta Cluj -Napoca /ID# 124945	Cluj-Napoca
Romania	S.C. Centrul de Oncologie Sf. Nectarie S.R.L. /ID# 124948	Craiova	Dolj
Romania	Oncomed SRL /ID# 127598	Timisoara
Russian Federation	Duplicate_archangel Clinical Oncology /ID# 126031	Arkhangelsk
Russian Federation	Altay Regional Oncological Dispesary /ID# 127160	Barnaul
Russian Federation	Belgorod Oncology Dispensary /ID# 129315	Belgorod
Russian Federation	Regional Oncology Dispensary /ID# 125936	Kursk	Tatarstan, Respublika
Russian Federation	Duplicate_Saratov State Medical University n.s. Chernyshevskiy /ID# 139395	Saratov
Russian Federation	LLC BioEq Ltd. /ID# 134529	St. Petersburg
Russian Federation	Siberian State Medical University /ID# 127161	Tomsk
Russian Federation	Volgograd Regional Clinical Oncology Dispensary /ID# 124952	Volzhsky
Russian Federation	Sverdlovsk Regional Oncology Dispensary /ID# 130950	Yekaterinburg	Sverdlovskaya Oblast
Singapore	Johns Hopkins Singapore IMC /ID# 125316	Singapore
Singapore	National University Hospital /ID# 125315	Singapore
South Africa	University of Free State, Universitas Annex (National Hospital Grounds) /ID# 128499	Bloemfontein	Free State
South Africa	Netcare Oncology Intervent Ctr /ID# 125320	Cape Town	Western Cape
South Africa	The Oncology Centre /ID# 126104	Durban	Kwazulu-Natal
South Africa	Cancercare Outeniqua Oncology Centre /ID# 125319	George	Western Cape
South Africa	GVI Oncology /ID# 125321	Gqeberha	Eastern Cape
South Africa	Medical Oncology Ctr Rosebank /ID# 125322	Johannesburg	Gauteng
South Africa	Sandton Oncology Medical Group PTY Ltd /ID# 125323	Johannesburg	Gauteng
South Africa	Wits Clinical Research Site /ID# 125317	Johannesburg	Gauteng
South Africa	Mary Potter Oncology Centre /ID# 133269	Pretoria	Gauteng
Spain	Hospital Santa Creu i Sant Pau /ID# 124963	Barcelona
Spain	Hospital General Universitario Gregorio Maranon /ID# 124962	Madrid
Spain	Hospital Universitario HM Sanchinarro /ID# 124960	Madrid
Spain	Hospital Universitario Virgen de la Victoria /ID# 124961	Malaga
Spain	Hospital Clinico Universitario de Valencia /ID# 124959	Valencia
Sweden	Sahlgrenska University Hospital /ID# 124965	Gothenburg	Vastra Gotalands Lan
Sweden	Linkoping University Hospital /ID# 126795	Linkoping
Sweden	Skane University hospital /ID# 124966	Malmo	Skane Lan
Sweden	Duplicate_Karolinska Univ Sjukhuset /ID# 124964	Solna
Sweden	Norrlands University hospital /ID# 124967	Umea	Vasterbottens Lan
Sweden	Uppsala University Hospital /ID# 126512	Uppsala
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 125575	Kaohsiung
Taiwan	National Taiwan University Hospital /ID# 125324	Taipei City
Turkey	Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi /ID# 125337	Ankara
Turkey	Hacettepe University Faculty of Medicine /ID# 125336	Ankara
Turkey	Duplicate_Akdeniz University Medical Fac /ID# 125339	Antalya
Turkey	Bezmi Alem Univ Med Fac Hosp /ID# 127901	Istanbul
Turkey	Istanbul University Istanbul Medical Faculty /ID# 145144	Istanbul
Ukraine	ME Kryviy Rih Oncology Dispensary /ID# 129806	?????? ???
Ukraine	Municipal Non-Profit Enterprise City Clinical Hospital No.4 of Dnipro City Counc /ID# 124968	Dnipro
Ukraine	Donetsk Regional Antitumor Ctr /ID# 124970	Donetsk
Ukraine	Communal non-profit enterprise Regional Center of Oncology /ID# 124972	Kharkiv
Ukraine	Lviv Oncological Regional Therapeutical and Diagnostic Centre /ID# 124974	Lviv
Ukraine	Poltava Regional Clinical Oncology Centre of Poltava Regional Council /ID# 124969	Poltava
Ukraine	Zaporizhzhia Med. Academy MOH /ID# 129800	Zaporizhia
United Kingdom	University Hospitals Birmingham NHS Foundation Trust /ID# 125342	Birmingham
United Kingdom	University Hospitals Bristol /ID# 128343	Bristol	Bristol, City Of
United Kingdom	Hull University Teaching Hospitals NHS Trust /ID# 133030	Hull	East Riding Of Yorkshire
United Kingdom	Nottingham University Hospitals NHS Trust /ID# 125340	Nottingham	Nottinghamshire
United States	University of New Mexico /ID# 125349	Albuquerque	New Mexico
United States	Lehigh Valley Health Network /ID# 130059	Allentown	Pennsylvania
United States	McFarland Clinic, PC /ID# 129904	Ames	Iowa
United States	Texas Health Physicians Group /ID# 137740	Arlington	Texas
United States	Mission Cancer Center /ID# 134248	Asheville	North Carolina
United States	Emory Midtown Infectious Disease Clinic /ID# 133192	Atlanta	Georgia
United States	Univ of Colorado Cancer Center /ID# 124983	Aurora	Colorado
United States	Johns Hopkins University /ID# 125015	Baltimore	Maryland
United States	Lehigh Valley Hosp/Muhlenberg /ID# 130277	Bethlehem	Pennsylvania
United States	Lynn Cancer Institute, Boca /ID# 125013	Boca Raton	Florida
United States	University of Vermont Medical Center /ID# 125350	Burlington	Vermont
United States	University of Illinois - Chicago /ID# 127576	Chicago	Illinois
United States	The Ohio State University /ID# 125022	Columbus	Ohio
United States	University of Texas Southwestern Medical Center /ID# 124989	Dallas	Texas
United States	The Cancer Ctr at DeKalb Med C /ID# 125024	Decatur	Georgia
United States	Saint Joseph Hospital /ID# 131768	Denver	Colorado
United States	Henry Ford Health System /ID# 134497	Detroit	Michigan
United States	City of Hope /ID# 127117	Duarte	California
United States	Duke Cancer Center /ID# 124999	Durham	North Carolina
United States	NorthShore University HealthSystem /ID# 124996	Evanston	Illinois
United States	Holy Cross Hospital /ID# 125012	Fort Lauderdale	Florida
United States	California Cancer Associates for Research & Excellence (cCARE) /ID# 136078	Fresno	California
United States	Banner MD Anderson Cancer Ctr /ID# 125011	Gilbert	Arizona
United States	Spectrum Health Medical Group /ID# 133568	Grand Rapids	Michigan
United States	Spectrum Health Medical Group /ID# 148471	Grand Rapids	Michigan
United States	Penn State University and Milton S. Hershey Medical Center /ID# 124997	Hershey	Pennsylvania
United States	University of Texas MD Anderson Cancer Center /ID# 125353	Houston	Texas
United States	Swedish Cancer Institute - Issaquah /ID# 131534	Issaquah	Washington
United States	Univ of Mississippi Med Ctr,US /ID# 131352	Jackson	Mississippi
United States	St. Lukes Cancer Institute /ID# 125023	Kansas City	Missouri
United States	Moores Cancer Center at UC San Diego /ID# 124991	La Jolla	California
United States	Nebraska Hematology Oncology /ID# 132711	Lincoln	Nebraska
United States	University of Arkansas for Medical Sciences /ID# 124992	Little Rock	Arkansas
United States	Rutgers Cancer Institute of New Jersey /ID# 125017	New Brunswick	New Jersey
United States	Beth Israel Medical Center /ID# 125001	New York	New York
United States	Mount Sinai St. Luke's /ID# 125003	New York	New York
United States	Hematology and Oncology Assoc /ID# 130058	Newport Beach	California
United States	Norwalk Hospital /ID# 133509	Norwalk	Connecticut
United States	Sacred Heart Hospital /ID# 128279	Pensacola	Florida
United States	Allegheny General Hospital /ID# 135094	Pittsburgh	Pennsylvania
United States	University of Pittsburgh MC /ID# 125005	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University /ID# 134229	Portland	Oregon
United States	William Beaumont Hospital /ID# 125019	Royal Oak	Michigan
United States	Washington University-School of Medicine /ID# 127575	Saint Louis	Missouri
United States	Cancer Research Collaboration /ID# 128860	Santa Ana	California
United States	Swedish Cancer Insititute - Ballard /ID# 131548	Seattle	Washington
United States	Swedish Cancer Institute - Edmonds /ID# 131549	Seattle	Washington
United States	Swedish Medical Center /ID# 125021	Seattle	Washington
United States	Baystate Medical Center /ID# 139461	Springfield	Massachusetts
United States	Northwest Medical Specialties - Tacoma /ID# 125344	Tacoma	Washington
United States	Moffitt Cancer Center /ID# 124990	Tampa	Florida
United States	University of Toledo /ID# 134849	Toledo	Ohio
United States	Florida Cancer Specialists - East /ID# 125007	West Palm Beach	Florida
United States	Icri /Id# 128520	Whittier	California
United States	UMass Chan Medical School /ID# 129067	Worcester	Massachusetts
United States	Midwestern Regional CTC /ID# 124986	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belarus,  Belgium,  Canada,  Chile,  Colombia,  Czechia,  Denmark,  Estonia,  Finland,  France,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  Latvia,  Lithuania,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Singapore,  South Africa,  Spain,  Sweden,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	Time to PFS is defined as the number of days from the date the participant was randomized to the date the participant experiences radiographic disease progression (as determined by the investigators), or to the date of death (all causes of mortality) if disease progression is not reached. All events of disease progression occurring on or before the Primary Analysis Cutoff date of 05 April 2019 were to be included, regardless of whether the event occurred while the participant was still taking study drug or had previously discontinued study drug. PFS was estimated for each treatment group using Kaplan-Meier methodology.	From randomization until the primary analysis data cut-off date of 05 April 2019; the median duration of follow-up was 35.5 months
Secondary	Overall Survival (OS)	Time to death (overall survival) is defined as the number of days from the date the participant was randomized to the date of the participant's death. All events of death which occur up to the analysis cutoff date are to be included, regardless of whether the event occurred while the participant was still taking study drug or after the participant discontinued study drug. If a participant has not died, the data for the participant is to be censored at the date last known to be alive or at the analysis cutoff date if that is earlier.; The final analysis of OS will occur when the pre-specified number of events has occurred in the ITT population.	Approximately 8 years from randomization
Secondary	Clinical Benefit Rate (CBR)	The clinical benefit rate (CBR) for each treatment group was to be obtained from a time-to-event analysis of radiographic disease progression per the investigator. CBR is defined as the progression-free rate at 24 weeks (168 days), estimated for each treatment arm using Kaplan Meier methodology. All events of disease progression in the primary progression free survival analysis database were to be included, regardless of whether the event occurred while the participant was still taking, or had previously discontinued, study drug. If the participant had not yet progressed then their data was to be censored at the date of the last evaluable disease progression assessment. Participants without post-baseline assessments were to be censored at the date of randomization.; The final analysis of CBR will occur when the pre-specified number of Overall Survival events have occurred in the ITT population, per the fixed sequence testing procedure.	Through the end of Week 24
Secondary	Objective Response Rate (ORR)	The objective response rate (ORR) is calculated as the percentage of participants who have a confirmed partial response (PR) or complete response (CR) based on assessment by the investigators per Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1. All participants who had at least one measurable lesion at baseline were to be included in the ORR calculation.; The final analysis of ORR will occur when the pre-specified number of Overall Survival events have occurred in the ITT population, per the fixed sequence testing procedure.	Approximately 8 years from randomization
Secondary	Progression-Free Survival on Subsequent Therapy (PFS2)	PFS2 is defined as the number of days from the date of randomization to the time of disease progression on subsequent therapy or death from any cause. The distribution of PFS2 was to be estimated for each treatment group using Kaplan-Meier methodology.; The final analysis of PFS2 will occur when the pre-specified number of Overall Survival events have occurred in the ITT population, per the fixed sequence testing procedure.	Approximately 8 years from randomization