Clinical trial NCT02032277: A Study Evaluating Safety and Efficacy of the Addition of ABT-888 Plus Carboplatin Versus the Addition of Carboplatin to Standard Chemotherapy Versus Standard Chemotherapy in Subjects With Early Stage Triple Negative Breast Cancer
Official title: A Randomized, Placebo-Controlled, Double-Blind, Phase 3 Study Evaluating Safety and Efficacy of the Addition of Veliparib Plus Carboplatin Versus the Addition of Carboplatin to Standard Neoadjuvant Chemotherapy Versus Standard Neoadjuvant Chemotherapy in Subjects With Early Stage Triple Negative Breast Cancer (TNBC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Triple Negative Breast Cancer
Keywords: Oncology
Triple negative breast cancer
German Breast Group - GBG 81
United States Oncology - 12152
National Surgical Adjuvant Breast and Bowel Project - B-56-I
Alliance - AFT-04
Grupo Español de Investigación en Cáncer de Mama - GEICAM/2014-02
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: GBG Forschungs GmbH
name: NSABP Foundation Inc
name: Grupo Español de Investigación del Cáncer de Mama
name: US Oncology Research
First posted: 2014-01-10
Enrollment: 634
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a 3 arm Phase 3 study to evaluate the safety and efficacy of the addition of veliparib plus carboplatin versus the addition of carboplatin to standard neoadjuvant chemotherapy versus standard neoadjuvant chemotherapy in subjects with early stage TNBC.


Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed invasive breast cancer by core needle or incisional biopsy (excisional biopsy is not allowed). Clinical stage T2-3 N0-2 or T1 N1-2 by physical exam or radiologic studies.
2. Documented Breast Cancer Gene (BRCA) germline mutation testing.
3. Estrogen Receptor (ER)-, Progesterone Receptor (PR)-, and Human Epidermal Growth Factor Receptor (HER)2-negative (triple-negative) cancer of the breast.
4. ECOG Performance status of 0 to 1.
5. Women must be determined to be not of childbearing potential (surgically sterile, or postmenopausal defined as amenorrheic for at least 12 months) by the Investigator OR they must have a negative serum pregnancy test prior to randomization.

Exclusion Criteria:

1. Previous anti-cancer treatment (cytotoxic chemotherapy, immunotherapy, biologic therapy radiotherapy or investigational agents) with therapeutic intent for current breast cancer.
2. Previous treatment with carboplatin, paclitaxel, doxorubicin, cyclophosphamide and a Poly-(ADP-ribose)-Polymerase (PARP) inhibitor.
3. Concurrent treatment with an ovarian hormonal replacement therapy or with hormonal agents such as raloxifene, tamoxifen or other selective estrogen receptor modulator (SERM). Subjects must have discontinued use of such agents prior to beginning study treatment.
4. A history of seizure within 12 months prior to study entry.
5. Pre-existing neuropathy from any cause in excess of Grade 1.

Primary outcomes:
measure: Pathological Complete Response (pCR).
timeFrame: At the time of definitive surgery (approximately 24-36 weeks from first dose of study drug).
Secondary outcomes:
measure: Event Free Survival (EFS)
timeFrame: Up to 4 years from the date of definitive surgery.
measure: Overall Survival (OS)
timeFrame: Up to 4 years from the date of definitive surgery.
measure: Rate of eligibility for breast conservation after therapy (BCR).
timeFrame: At the time of definitive surgery (approximately 24-36 weeks from first dose of study drug).
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Scottsdale Healthcare /ID# 120473
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic - Scottsdale /ID# 139932
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC-HOPE /ID# 126137
state: Arizona
city: Los Angeles
country: United States
facility: Usc /Id# 123310
state: California
city: Salinas
country: United States
facility: Pacific Cancer Care /ID# 120476
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital /ID# 119861
state: California
city: Stanford
country: United States
facility: Stanford University School of Med /ID# 130316
state: California
city: West Hollywood
country: United States
facility: Cedars-Sinai Medical Center - West Hollywood /ID# 137275
state: California
city: Newark
country: United States
facility: Christiana Care Health Service /ID# 137823
state: Delaware
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - Fort Myers /ID# 121835
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - Fort Myers /ID# 126379
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic /ID# 132349
state: Florida
city: Miami
country: United States
facility: Mount Sinai Comp Cancer Ctr /ID# 133008
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute - Baptist Health South Florida /ID# 126145
state: Florida
city: Orlando
country: United States
facility: UF Health Cancer Center /ID# 141589
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center /ID# 124063
state: Florida
city: Chicago
country: United States
facility: University of Illinois - Chicago /ID# 134329
state: Illinois
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine /ID# 133848
state: Illinois
city: Chicago
country: United States
facility: University of Chicago DCAM /ID# 120467
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Ctr /ID# 120455
state: Illinois
city: Rockford
country: United States
facility: OSF St. Anthony Medical Center /ID# 139424
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ School Medicine /ID# 118215
state: Indiana
city: Indianapolis
country: United States
facility: Community Rgnal Cancer Care N /ID# 120456
state: Indiana
city: Lafayette
country: United States
facility: Horizon Oncology Research Center /ID# 116815
state: Indiana
city: Wichita
country: United States
facility: Cancer Center of Kansas /ID# 134720
state: Kansas
city: Baltimore
country: United States
facility: Univ Maryland School Medicine /ID# 119235
state: Maryland
city: Ypsilanti
country: United States
facility: St. Joseph Mercy Hospital /ID# 135875
state: Michigan
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, PA /ID# 126144
state: Minnesota
city: Kansas City
country: United States
facility: St. Lukes Cancer Institute /ID# 118775
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Ctrs Neva /ID# 126136
state: Nevada
city: Manchester
country: United States
facility: Solinksy Center for Cancer Care /ID# 131970
state: New Hampshire
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of NJ /ID# 120477
state: New Jersey
city: New York
country: United States
facility: Columbia Univ Medical Center /ID# 141588
state: New York
city: Asheville
country: United States
facility: Hope Womens Cancer Centers /ID# 119179
state: North Carolina
city: Chapel Hill
country: United States
facility: Univ NC Chapel Hill /ID# 132893
state: North Carolina
city: Chapel Hill
country: United States
facility: Univ NC Chapel Hill /ID# 147695
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Oncology Special /ID# 139890
state: North Carolina
city: Fargo
country: United States
facility: Sanford Roger Maris Cancer Cen /ID# 132394
state: North Dakota
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc - Blue Ash /ID# 120478
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center /ID# 141691
state: Ohio
city: Cleveland
country: United States
facility: Fairview Hospital /ID# 141626
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Main Campus /ID# 126378
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University /ID# 141587
state: Ohio
city: Allentown
country: United States
facility: Lehigh Valley Health Network /ID# 133372
state: Pennsylvania
city: Sayre
country: United States
facility: Guthrie Medical Group, PC /ID# 124397
state: Pennsylvania
city: Providence
country: United States
facility: Women and Infants Hospital /ID# 123476
state: Rhode Island
city: Sioux Falls
country: United States
facility: Avera Cancer Institute /ID# 120466
state: South Dakota
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC /ID# 124566
state: Tennessee
city: Bedford
country: United States
facility: Texas Oncology - Bedford /ID# 126135
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Medical City Dallas /ID# 126140
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Medical City Dallas /ID# 126141
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center /ID# 133849
state: Texas
city: Fort Worth
country: United States
facility: The Ctr for Cancer and Blood D /ID# 120479
state: Texas
city: Houston
country: United States
facility: Texas Oncology - Memorial City /ID# 126139
state: Texas
city: Plano
country: United States
facility: Texas Oncology - Plano East /ID# 126143
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler /ID# 126142
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah /ID# 118677
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia /ID# 122975
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth Univ /ID# 141586
state: Virginia
city: Virginia Beach
country: United States
facility: Virginia Oncology Associates /ID# 127260
state: Virginia
city: Madison
country: United States
facility: Univ of Wisconsin Hosp/Clinics /ID# 120457
state: Wisconsin
city: Tweed Heads
country: Australia
facility: The Tweed Hospital /ID# 120235
state: New South Wales
city: Malvern
country: Australia
facility: Cabrini Health /ID# 120236
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital /ID# 127717
state: Victoria
city: St. Albans
country: Australia
facility: Western Health Sunshine Hosp. /ID# 120715
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital /ID# 120716
state: Western Australia
city: Murdoch
country: Australia
facility: St. John of God Hosp - Murdoch /ID# 131788
state: Western Australia
city: Subiaco
country: Australia
facility: St. John of God Subiaco Hosp /ID# 120717
state: Western Australia
city: Woluwe-Saint-Lambert
country: Belgium
facility: Cliniques Universitaires Saint Luc /ID# 120719
state: Bruxelles-Capitale
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi /ID# 116678
state: Hainaut
city: Brussels
country: Belgium
facility: CHU Brugmann /ID# 120376
city: Edegem
country: Belgium
facility: UZ Antwerp /ID# 120720
city: Kortrijk
country: Belgium
facility: AZ Groeninge /ID# 120718
city: Namur
country: Belgium
facility: CHU UCL Namur /ID# 116677
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Ctr /ID# 123312
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital /ID# 141629
state: Quebec
city: Montréal
country: Canada
facility: CHUM - Notre-Dame Hospital /ID# 141694
state: Quebec
city: Quebec City
country: Canada
facility: CHUQ-Hospital St. Sacrement /ID# 141619
state: Quebec
city: Olomouc
country: Czechia
facility: Fakultni Nemocnice Olomouc /ID# 120725
state: Olomoucky Kraj
city: Brno
country: Czechia
facility: Masarykuv onkologikcy ustav /ID# 120726
city: Hradec Kralove
country: Czechia
facility: FN Hradec Kralove /ID# 120596
city: Toulouse
country: France
facility: Hopital Universitaire Purpan /ID# 120731
state: Haute-Garonne
city: Lille
country: France
facility: Centre Oscar Lambret /ID# 119958
state: Hauts-de-France
city: Paris CEDEX 05
country: France
facility: Institut Curie /ID# 116679
state: Ile-de-France
city: Lyon CEDEX 08
country: France
facility: Centre Leon Berard /ID# 120740
state: Rhone
city: Clermont Ferrand
country: France
facility: Jean Perrin Centre /ID# 125277
city: Paris
country: France
facility: Hosp European, Georges Pompid /ID# 120736
city: Saint-cloud
country: France
facility: Hopital Rene Huguenin /ID# 120729
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein /ID# 133454
state: Schleswig-Holstein
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm /ID# 133453
state: Thueringen
city: Augsburg
country: Germany
facility: Gemeinschaftspraxis Dr. Heinrich und Prof. Bangerter /ID# 133472
city: Berlin
country: Germany
facility: Helios Klinikum Berlin Buch /ID# 133465
city: Bielefeld
country: Germany
facility: Studiengesellschaft Onk Bielef /ID# 133471
city: Bremen
country: Germany
facility: Klinikum Bremen Mitte gGmbH /ID# 132875
city: Dortmund
country: Germany
facility: St. Johannes Hospital /ID# 133478
city: Esslingen
country: Germany
facility: Kliniken Esslingen /ID# 133475
city: Frankfurt
country: Germany
facility: Klinikum Frankfurt Hoechst /ID# 145301
city: Fürth
country: Germany
facility: Wilke/Wagner/Petzoldt, Fuerth /ID# 133481
city: Gelsenkirchen
country: Germany
facility: Evangelisches Krankenhaus /ID# 133457
city: Kassel
country: Germany
facility: Elisabeth Krankenhaus /ID# 133461
city: Limburg
country: Germany
facility: St. Vincenz Krankenhaus /ID# 133466
city: Munich
country: Germany
facility: Onk Zentrum am Rotkreuz /ID# 133482
city: Munich
country: Germany
facility: Klinikum recht der Isar der TU /ID# 133449
city: Offenbach
country: Germany
facility: Sana Klinikum Offenbach /ID# 133455
city: Schweinfurt
country: Germany
facility: Leopoldina-Krankenhaus /ID# 133484
city: Stendal
country: Germany
facility: Johanniter-Krankenhaus Genthin /ID# 133463
city: Wiesbaden
country: Germany
facility: St. Josefs-Hospital /ID# 133464
city: Witten
country: Germany
facility: Marienhospital Witten /ID# 133470
city: Budapest
country: Hungary
facility: National Institute of Oncology /ID# 120828
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont /ID# 120834
city: Budapest
country: Hungary
facility: Uzsoki Utcai Korhaz /ID# 120825
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont /ID# 116681
city: Gyor
country: Hungary
facility: Petz Aladar Megyei Oktato Korh /ID# 120835
city: Kecskemét
country: Hungary
facility: Bacs-Kiskun Megyei Korhaz /ID# 120833
city: Miskolc
country: Hungary
facility: BAZ Megyei E.O. Korhaz /ID# 122215
city: Szeged
country: Hungary
facility: University of Szeged /ID# 120823
city: Szolnok
country: Hungary
facility: Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz /ID# 120818
city: Bologna
country: Italy
facility: A.O.U. Policlinico S.Orsola-Malpighi /ID# 122855
state: Emilia-Romagna
city: Grosseto
country: Italy
facility: Misericordia General Hospital /ID# 119536
city: Meldola
country: Italy
facility: IRCCS-I.R.S.T. srl Meldola /ID# 120255
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia /ID# 120845
city: Pavia
country: Italy
facility: IRCCS Fondazione Salva Maugeri /ID# 120848
city: Goyang
country: Korea, Republic of
facility: National Cancer Center /ID# 119525
state: Gyeonggido
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital /ID# 118856
state: Gyeonggido
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital /ID# 118855
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Severance Hospital /ID# 116699
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center /ID# 119276
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital /ID# 118857
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 116698
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center /ID# 116696
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum /ID# 126302
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Scientific Institution N.N. Blokhin Russian Cancer Resea /ID# 120944
state: Moskva
city: Kursk
country: Russian Federation
facility: Kursk Regional Oncology Dispen /ID# 116688
state: Tatarstan, Respublika
city: Arkhangelsk
country: Russian Federation
facility: archangel Clinical Oncology /ID# 120935
city: Obninsk
country: Russian Federation
facility: Medical Radiological Res Ctr /ID# 124017
city: Pyatigorsk
country: Russian Federation
facility: Pyatigorsk Oncology Dispensary /ID# 120945
city: St. Petersburg
country: Russian Federation
facility: Leningrad Reg Onc Dispensery /ID# 120938
city: St. Petersburg
country: Russian Federation
facility: Birch A Healthcare /ID# 116695
city: A Coruña
country: Spain
facility: Hospital Universitario A Coruña - CHUAC /ID# 135108
state: A Coruna
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol /ID# 135112
state: Barcelona
city: Alicante
country: Spain
facility: Hospital General Universitario Alicante /ID# 135115
city: Barcelona
country: Spain
facility: Hospital Parc de Salut del Mar /ID# 135110
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau /ID# 145400
city: Lleida
country: Spain
facility: Hospital Universitario Arnau de Vilanova de Lleida /ID# 120979
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal /ID# 135113
city: Madrid
country: Spain
facility: Hospital Clinico Universitario San Carlos /ID# 119959
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio /ID# 135114
city: Valencia
country: Spain
facility: Fundacion Instituto Valenciano Oncologia IVO /ID# 135116
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia /ID# 123076
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia /ID# 135111
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet /ID# 119195
city: Taipei City
country: Taiwan
facility: National Taiwan Univ Hosp /ID# 122895
state: Taipei
city: Changhua County
country: Taiwan
facility: Changhua Christian Hospital /ID# 119085
city: Tainan City
country: Taiwan
facility: Chi Mei Hospital - Liouying /ID# 120982
city: Bristol
country: United Kingdom
facility: Univ Hosp Bristol NHS Foundati /ID# 120989
city: London
country: United Kingdom
facility: Charing Cross Hospital /ID# 120990
city: Nottingham
country: United Kingdom
facility: Nottingham Univ Hospitals NHS /ID# 122218
city: Stoke on Trent
country: United Kingdom
facility: Royal Stoke Univ Hospital /ID# 120984
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: Filho OM, Stover DG, Asad S, Ansell PJ, Watson M, Loibl S, Geyer CE Jr, Bae J, Collier K, Cherian M, O'Shaughnessy J, Untch M, Rugo HS, Huober JB, Golshan M, Sikov WM, von Minckwitz G, Rastogi P, Maag D, Wolmark N, Denkert C, Symmans WF. Association of Immunophenotype With Pathologic Complete Response to Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer: A Secondary Analysis of the BrighTNess Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):603-608. doi: 10.1001/jamaoncol.2020.7310.
citation: Golshan M, Loibl S, Wong SM, Houber JB, O'Shaughnessy J, Rugo HS, Wolmark N, McKee MD, Maag D, Sullivan DM, Metzger-Filho O, Von Minckwitz G, Geyer CE Jr, Sikov WM, Untch M. Breast Conservation After Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer: Surgical Results From the BrighTNess Randomized Clinical Trial. JAMA Surg. 2020 Mar 1;155(3):e195410. doi: 10.1001/jamasurg.2019.5410. Epub 2020 Mar 18.
citation: Golshan M, Wong SM, Loibl S, Huober JB, O'Shaughnessy J, Rugo HS, Wolmark N, Ansell P, Maag D, Sullivan DM, Metzger-Filho O, Von Minckwitz G, Geyer CE Jr, Sikov WM, Untch M. Early assessment with magnetic resonance imaging for prediction of pathologic response to neoadjuvant chemotherapy in triple-negative breast cancer: Results from the phase III BrighTNess trial. Eur J Surg Oncol. 2020 Feb;46(2):223-228. doi: 10.1016/j.ejso.2019.10.002. Epub 2019 Oct 5.
citation: Loibl S, O'Shaughnessy J, Untch M, Sikov WM, Rugo HS, McKee MD, Huober J, Golshan M, von Minckwitz G, Maag D, Sullivan D, Wolmark N, McIntyre K, Ponce Lorenzo JJ, Metzger Filho O, Rastogi P, Symmans WF, Liu X, Geyer CE Jr. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol. 2018 Apr;19(4):497-509. doi: 10.1016/S1470-2045(18)30111-6. Epub 2018 Feb 28.