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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02163694
Recruitment Status : Active, not recruiting
First Posted : June 16, 2014
Last Update Posted : January 26, 2018
Information provided by (Responsible Party):

Brief Summary:
The study seeks to evaluate the efficacy and tolerability of veliparib/placebo in combination with carboplatin and paclitaxel in HER2-negative metastatic or locally advanced, unresectable, BRCA-associated breast cancer.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: Paclitaxel Drug: Veliparib Drug: Carboplatin Other: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 512 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : August 5, 2014
Estimated Primary Completion Date : May 31, 2018
Estimated Study Completion Date : May 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Arm Intervention/treatment
Placebo Comparator: Placebo with Carboplatin and Paclitaxel
Placebo on Day -2 through 5 of a 21-day cycle. In addition, carboplatin and paclitaxel will be administered on Day 1 of a 21-day cycle.
Drug: Paclitaxel
Day 1 of 21-day cycle
Other Name: Taxol
Drug: Carboplatin
Day 1 of 21-day cycle
Other: Placebo
Placebo on Day -2 through 5 of a 21-day cycle. In addition, carboplatin and paclitaxel will be administered on Day 1 of a 21-day cycle.
Experimental: Veliparib with Carboplatin and Paclitaxel
Veliparib on Day -2 through 5 of a 21-day cycle. In addition, carboplatin and paclitaxel will be administered on Day 1 of a 21-day cycle.
Drug: Paclitaxel
Day 1 of 21-day cycle
Other Name: Taxol
Drug: Veliparib
Veliparib on Day -2 through 5 of a 21-day cycle. In addition, carboplatin and paclitaxel will be administered on Day 1 of a 21-day cycle.
Other Name: ABT-888
Drug: Carboplatin
Day 1 of 21-day cycle

Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
    Number of days from the date the subject is randomized to the date the subject experiences a confirmed event of disease progression or to the date of death if disease progression is not reached

Secondary Outcome Measures :
  1. Duration of overall response (DOR) [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
    Number of days from the day the criteria are met for complete response or partial response (whichever is recorded first) to the date of progressive disease

  2. Progression-free survival 2 (PFS2) [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
    Days from randomization to the second objective radiographic progression or death of any cause after the first objective radiographic progression, whichever occurs first

  3. Objective response rate (ORR) [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
    Proportion of subjects with a complete or partial objective response

  4. Overall survival (OS) [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
    Number of days from the day the subject is randomized to the date of the subject's death

  5. Clinical benefit rate (CBR) [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
    Progression-free rate at 24 weeks from the Kaplan-Meier curve for time to progression

Other Outcome Measures:
  1. Change in quality of life (QOL) [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
    Assessed via survey

  2. Change in Eastern Cooperative Oncology Group (ECOG) Performance Status [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
    Change in ECOG performance status

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 BRCA1 and/or BRCA2 germline mutation.
  3. Breast cancer must be 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. 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 or neoadjuvant).
  3. Prior therapy with 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02163694

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United States, California
City of Hope
Duarte, California, United States, 91010
American Institute of Research
Long Beach, California, United States, 90805
Hematology and Oncology Assoc
Newport Beach, California, United States, 92663
San Diego, California, United States, 92122
Cancer Research Collaboration,
Santa Ana, California, United States, 92705
Whittier, California, United States, 90603
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
Saint Joseph Hospital
Denver, Colorado, United States, 80218
United States, Connecticut
Norwalk Hospital
Norwalk, Connecticut, United States, 06856
United States, Florida
Lynn Cancer Institute, Boca
Boca Raton, Florida, United States, 33486
Moffitt Cancer Center
Tampa, Florida, United States, 33612
Florida Cancer Specialists
West Palm Beach, Florida, United States, 33401
United States, Georgia
Emory University Hospital
Atlanta, Georgia, United States, 30322
The Cancer Ctr at DeKalb Med C
Decatur, Georgia, United States, 30033
United States, Illinois
University of Illinois
Chicago, Illinois, United States, 60607
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Baystate Medical Center
Springfield, Massachusetts, United States, 01199
UMass Memorial Medical Center
Worcester, Massachusetts, United States, 01655
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
Spectrum Health Medical Group
Grand Rapids, Michigan, United States, 49503
William Beaumont Hospital
Royal Oak, Michigan, United States, 48073
United States, Missouri
St. Lukes Cancer Institute
Kansas City, Missouri, United States, 64111
Washington Univ School Med
Saint Louis, Missouri, United States, 63110
United States, Nebraska
Nebraska Hematology Oncology
Lincoln, Nebraska, United States, 68506
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87102
United States, New York
Beth Israel Medical Center
New York, New York, United States, 10003
St. Lukes Roosevelt Hosp Ctr
New York, New York, United States, 10025
United States, North Carolina
Cancer Care of WNC, PA
Asheville, North Carolina, United States, 28801
Duke Univ Med Ctr
Durham, North Carolina, United States, 27710
United States, Ohio
University of Toledo
Toledo, Ohio, United States, 43614
United States, Oregon
Oregon Health and Science Univ
Portland, Oregon, United States, 97239-3011
United States, Pennsylvania
Penn State University and Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Pittsburgh, Pennsylvania, United States, 15260
United States, Texas
Texas Health Physicians Group
Arlington, Texas, United States, 76012
UT Southwestern Medical Center
Dallas, Texas, United States, 75235
Univ TX, MD Anderson
Houston, Texas, United States, 77030
United States, Vermont
Fletcher Allen Health Care, In
Burlington, Vermont, United States, 05401
United States, Washington
Swedish Cancer Institute
Seattle, Washington, United States, 98104
Swedish Medical Center
Seattle, Washington, United States, 98104
Northwest Medical Specialties
Tacoma, Washington, United States, 98405
Berazategui, Buenos Aires, Argentina, 1884
Centro Oncologico Riojano
La Rioja, Argentina, 5300
Centro Investigacion Pergamino
Pergamino, Argentina, 2700
Instituto de Oncologia de Rosa
Rosario, Santa FE, Argentina, 2000
Australia, New South Wales
St George Hospital
Kogarah, New South Wales, Australia, 2217
The Prince of Wales Hospital
Randwick, New South Wales, Australia, 2031
Southern Medical Day Care Ctr
Wollongong, New South Wales, Australia, 2500
Australia, Queensland
The Townsville Hospital
Douglas, Queensland, Australia, 4814
Australia, South Australia
Flinders Centre for Innovation
Adelaide, South Australia, Australia, 5042
Australia, Tasmania
Royal Hobart Hospital
Hobart, Tasmania, Australia, 7000
Australia, Victoria
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Australia, Western Australia
Hollywood Private Hospital
Nedlands, Western Australia, Australia, 6009
LKH-Univ. Klinikum Graz
Graz, Austria, 8036
KH der Elisabethinen Linz GmbH
Linz, Austria, 4020
LKH Salzburg and Paracelsus
Salzburg, Austria, 5020
Medical University of Vienna
Vienna, Austria, 1090
Bobruysk Interdistrict Onco.
Bobruisk, Belarus, 213825
Rep Res and Practice Ctr Onc
Lesnoy, Belarus, 223040
Mogilev Reg Clin Oncology Dis
Mogilev, Belarus, 212018
Vitebsk Reg Clin Onc Disp
Vitebsk, Belarus, 210603
ZNA Middelheim
Antwerp, Belgium, 2020
Cliniques Univ. Saint Luc
Brussels, Belgium, 1200
Grand Hopital de Charleroi
Charleroi, Belgium, 6000
UZ Antwerp
Edegem, Belgium, 2650
UZ Leuven
Leuven, Belgium, 3000
Namur, Belgium, 5000
Canada, Ontario
Sunnybrook Health Sciences Ctr
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
CHUM - Notre-Dame Hospital
Montreal, Quebec, Canada, H2L 4M1
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
CHUQ-Hospital St. Sacrement
Quebec City, Quebec, Canada, G1S 4L8
Instituto Nacional del Cancer
Santiago, Chile, 1010
ICOS - Inst Clinic Oncology
Temuco, Chile, 4810469
Hospital Clinico Vina del Mar
Vina Del Mar, Chile, 2520612
Administradora del Country_S.A-Clinica Del Country
Bogota, Cundinamarca, Colombia, 110221
Hospital Univ San Ignacio
Bogota, Colombia, 110231
Centro Medico Imbanaco de Cali
Cali, Colombia
Hospital Pablo Tobon Uribe
Medellín, Colombia
Inst Med Alta Tec Onc (IMAT)
Monteria, Colombia
Fakultni Nemocnice Brno
Brno, Czechia, 625 00
Masarykuv onkologikcy ustav
Brno, Czechia, 656 53
Fakultni Nemocnice Olomouc
Olomouc, Czechia, 779 00
Vseobecna Fakultni Nemocnice
Prague, Czechia, 128 08
Rigshospitalet, Finsen Centre
Copenhagen, Denmark, 2100
Vejle Sygehus
Vejle, Denmark, 7100
East Tallinn Central Hospital
Tallinn, Estonia, 10138
Docrates Cancer Center
Helsinki, Finland, 00180
Helsinki Univ Central Hospital
Helsinki, Finland, 00290
Tampere University Hospital
Tampere, Finland, 33521
Vaasa Central Hospital
Vaasa, Finland, 65130
Institut de Cancer de l'Ouest
St Herblain CEDEX, Loire-Atlantique, France, 44805
Institut Paoli-Calmettes
Marseille, France, 13273
Institut Curie
Paris, France, 75248
Hopital Rene Huguenin
Saint-cloud, France, 92210
Uniklinik Koln
Köln, Nordrhein-Westfalen, Germany, 50937
Universitaetklinikum Dresden
Dresden, Germany, 01307
Universitaetsklinik Heidelberg
Heidelberg, Germany, 69120
Klinikum recht der Isar der TU
Munich, Germany, 80802
Sana Klinikum Offenbach
Offenbach, Germany, 63069
Universitatsklinikum Tubingen
Tuebingen, Germany, 72076
Universitaetsklinikum Ulm
Ulm, Germany, 89081
Pecsi Tudomanyegyetem
Pécs, Pecs, Hungary, 7624
Semmelweis Egyetem
Budapest, Hungary, 1085
Jasz-Nagykun-Szolnok Megyei
Szolnok, Hungary, 5004
Zala Megyei Korhaz
Zalaegerszeg, Hungary, 8900
Soroka Medical Ctr
Be'er Sheva, Israel, 84101
Assaf Harofeh Medical Center
Be'er Ya'akov, Israel, 70300
Rambam Health Care Campus
Haifa, Israel, 3109601
Shaare Zedek Medical Center
Jerusalem, Israel, 91031
Hadassah University Hospital
Jerusalem, Israel, 91120
Sheba Medical Center
Ramat Gan, Israel, 5262100
Kaplan Medical Center
Rehovot, Israel, 76100
Tel Aviv Sourasky Medical Ctr
Tel Aviv, Israel, 64239
Centro di Riferimento Oncologi
Aviano, Italy, 33081
Ospedale San Raffaele IRCCS
Milan, Italy, 20132
Istituto Europeo di Oncologia
Milan, Italy, 20141
AO Bianchi Melacrino Morelli
Reggio Calabria, Italy, 89125
Korea, Republic of
National Cancer Center
Goyang, Gyeonggido, Korea, Republic of, 10408
Seoul National University Hospital
Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03080
Asan Medical Center
송파구, Seoul Teugbyeolsi, Korea, Republic of, 05505
Korea University Anam Hospital
Seoul, Korea, Republic of, 02841
Severance Hospital
Seoul, Korea, Republic of, 120-752
Samsung Medical Center
Seoul, Korea, Republic of, 135-710
Riga East Clinical Univ Hosp
Riga, Latvia, 1038
P. Stradins Clinical Univ Hosp
Riga, Latvia, LV-1002
Hosp Lithuanian Univ Health Sc
Kaunas, Lithuania, 50009
National Cancer Institute
Vilnius, Lithuania, 08661
Centro Oncologico de Chihuahua
Chihuahua, Mexico, 31217
Centro Multidisciplinario para
Mérida, Mexico, 97133
Instituto Nacional del Cancer
Tlapan, Mexico, 14080
Univ Med Center Groningen
Groningen, Netherlands, 9713 GZ
Maastricht University Med Ctr
Maastricht, Netherlands, 6229 HX
Erasmus Medisch Centrum
Rotterdam, Netherlands, 3015 CE
Haukeland University Hospital
Bergen, Norway, 5021
Centrum Onkologii Lukaszczyka
Bydgoszcz, Poland, 85-796
Wojewodzki Szpital Zespolony
Elblag, Poland, 82-300
Wojewodzkie Wielospecjalistycz
Lodz, Poland, 93-509
Mrukmed. Lekarz Beata Madej
Rzeszow, Poland, 35-922
Wojewodzki Szpital Specjalisty
Wroclaw, Poland, 51-124
Centro Hospitalar do Algarve
Faro, Portugal, 8000-386
Centro Hosp de Lisbon Norte
Lisbon, Portugal, 1649-035
Unidade Local Saude Matosinhos
Matosinhos, Portugal, 4464-513
Instituto Portugues Oncologia
Porto, Portugal, 4200-072
Centro Hospitalar de Sao Joao, EPE
Porto, Portugal, 4200-319
Centro Hospitalar De Vila Nova
Porto, Portugal, 4434-502
Puerto Rico
Ad-Vance Medical Research, LLC
Ponce, Puerto Rico, 00717
lnstitutul Oncologic Trestiore
Bucharest, Romania, 022328
Spitalul Clinic Judetean de Ur
Cluj, Romania, 400006
Sc Oncolab Srl
Craiova, Romania, 200385
Oncomed SRL
Timisoara, Romania, 300239
Russian Federation
Sverdlovsk Regional Oncology Center
Ekaterinburg, Sverdlovskaya Oblast, Russian Federation, 620043
Kursk Regional Oncology Dispen
Kursk, Tatarstan, Respublika, Russian Federation, 305035
archangel Clinical Oncology
Arkhangelsk, Russian Federation, 163045
Altay Regional Oncologic Disp
Barnaul, Russian Federation, 656049
Belgorod Oncology Dispensary
Belgorod, Russian Federation, 308010
GBOU VPO Saratov State Med Uni
Saratov, Russian Federation, 410012
LLC BioEq Ltd.
St. Petersburg, Russian Federation, 197342
Federal state budget education
Tomsk, Russian Federation, 634050
Volgograd Reg Onc Disp #3
Volzhsky, Russian Federation, 404130
National University Hospital
Singapore, Singapore, 119074
Gleneagles Medical Centre
Singapore, Singapore, 258499
Johns Hopkins Singapore IMC
Singapore, Singapore, 308433
South Africa
GVI Oncology
Port Elizabeth, Eastern Cape, South Africa, 6006
Universitas Annexe
Bloemfontein, Free State, South Africa, 9320
Medical Oncology Ctr Rosebank
Johannesburg, Gauteng, South Africa, 2196
Sandton Oncology Centre
Johannesburg, Gauteng, South Africa, 2199
Mary Potter Oncology Centre
Pretoria, Gauteng, South Africa, 0181
The Oncology Centre
Durban, Kwazulu-Natal, South Africa, 4091
Netcare Oncology Intervent Ctr
Cape Town, Western Cape, South Africa, 7460
GVI Outeniqua Oncology Unit
George, Western Cape, South Africa, 6530
Hosp Santa Creu i Sant Pau
Barcelona, Spain, 08026
Hospital Genl Gregorio Maranon
Madrid, Spain, 28007
Hosp Univ Madrid Sanchinarro
Madrid, Spain, 28050
Hosp Uni Virgen de la Victoria
Malaga, Spain, 29010
Hosp Clin Univ de Valencia
Valencia, Spain, 46010
Sahlgrenska University Hosp
Goteborg, Sweden, 413 45
Skanes Universitetssjukhus
Malmo, Sweden, 205 02
Karolinska Univ Sjukhuset
Solna, Sweden, 17176
Norrlands Universitetssjukhus
Umeå, Sweden, 90185
Uppsala University Hospital
Uppsala, Sweden, 75185
Kaohsiung Medical University
Kaohsiung, Taiwan, 80708
National Taiwan Univ Hosp
Taipei City, Taiwan, 10002
Hacettepe Univ Med Faculty
Ankara, Turkey, 06230
Dr. Abdurrahman Yurtaslan
Ankara, Turkey, 6200
Akdeniz University Medical Fac
Antalya, Turkey, 07059
Bezmi alem Vakif Universitesi
Istanbul, Turkey, 34093
Istanbul University Cerrahpasa Medical Faculty
Istanbul, Turkey, 34098
Istanbul Medeniyet Universites
Istanbul, Turkey, 34722
Cherkassy Regional Onc Ctr
Cherkasy, Ukraine, 18000
City Multi-Field Clin Hosp #4
Dnipropetrovsk, Ukraine, 49102
Kharkiv Regional Clinical Onco
Kharkiv, Ukraine, 61070
Kryorizskiy Oncology Dispensa
Kryvyi Rih, Ukraine, 50048
Lviv State Onc Local Treatment
Lviv, Ukraine, 79031
Poltava Regional Clinical Onco
Poltava, Ukraine, 36011
Zaporizhzhia Med. Academy MOH
Zaporizhia, Ukraine, 69040
United Kingdom
University of Birmingham
Birmingham, United Kingdom, B15 2TT
Bristol Haematology and Onc Ct
Bristol, United Kingdom, BS2 8ED
Castle Hill Hospital
Cottingham, United Kingdom, HU16 5JQ
Nottingham Univ Hospitals NHS
Nottingham, United Kingdom, NG5 1PB
Sponsors and Collaborators
Study Director: AbbVie Inc. AbbVie

Additional Information:
Responsible Party: AbbVie Identifier: NCT02163694     History of Changes
Other Study ID Numbers: M12-914
2014-000345-70 ( EudraCT Number )
First Posted: June 16, 2014    Key Record Dates
Last Update Posted: January 26, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by AbbVie:
PARP Inhibitor
Locally recurrent
Breast Cancer
Metastatic Breast Cancer
Genetic breast cancer
BRCA Mutation

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Albumin-Bound Paclitaxel
Poly(ADP-ribose) Polymerase Inhibitors
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors