Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer) (tnAcity)

A Phase 2/3, Multi-Center, Open-Label, Randomized Study of Weekly Nab®-Paclitaxel in Combination With Gemcitabine or Carboplatin, Compared to Gemcitabine/Carboplatin, as First Line Treatment in Subjects With ER, PgR, and HER2 Negative (Triple Negative) Metastatic Breast Cancer

The purpose of this study is to compare the safety and efficacy of nab-paclitaxel in combination with either gemcitabine or carboplatin to the combination of gemcitabine and carboplatin as first line treatment in female subjects with triple negative metastatic breast cancer (TNMBC) or metastatic triple negative breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Metastatic Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer; Recurrent Breast Cancer; Breast Tumor; Cancer of the Breast; Triple-negative Metastatic Breast Cancer; Estrogen Receptor- Negative Breast Cancer; HER2- Negative Breast Cancer; Progesterone Receptor- Negative Breast Cancer
• Intervention / Treatment: Drug: nab-Paclitaxel; Drug: Gemcitabine; Drug: Carboplatin

Detailed Description

ABI-007-MBC- 001 is a Phase 2/3, multicenter, open-label, randomized, study that will compare the safety and efficacy of weekly nab-paclitaxel in combination with gemcitabine or carboplatin to the combination of gemcitabine and carboplatin as first line therapy in female subjects with Estrogen Receptor (ER), Progesterone Receptor (PgR), and human epidermal growth factor receptor 2 (HER2) negative (triple negative) metastatic breast cancer (TNMBC) or metastatic triple negative breast cancer. In the phase 2 portion of the study, the combinations of nab-paclitaxel plus gemcitabine and nab-paclitaxel plus carboplatin will be evaluated, and a comparator arm of gemcitabine combined with carboplatin will be used. In the phase 3 portion of the study, the selected nab-paclitaxel combination treatment will be compared to gemcitabine combined with carboplatin to evaluate progression free survival, safety and tolerability, overall survival, disease control rate and duration of response in women with metastatic triple negative breast cancer.

Due to changes in the treatment landscape since the initiation of this trial, the decision was made not to proceed to the Phase 3 portion of the study.

• Study Type: Interventional
• Enrollment (Actual): 191
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Nedlands, Australia, 6009
    • Sir Charles Gairdner Hospital
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • Canberra Hospital
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Frankston Hospital Oncology Research
    • Wodonga, Victoria, Australia, 3690
      • Border Medical Oncology
• Austria
  • Innsbruck, Austria, 6020
    • Universitaetsklinik Innsbruck
  • Salzburg, Austria, 5020
    • Salzburger Landkliniken St. Johanns-Spital
  • Vienna, Austria, 1090
    • Medizinische Universität Wien
• Brazil
  • Fortaleza, Brazil, 60160-230
    • ONCOCLINIC Clinica de Oncologia LTDA
  • Ribeirao Preto, Brazil, 14015-130
    • Instituto Ribeiraopretano de Combate Ao Cancer
  • Ribeirao Preto, Brazil, 14048-900
    • Hospital Das Clinicas Da Faculdade De Medicina Da USP
  • Rio Grande Do Sul, Brazil, 95900-000
    • Hospital Bruno Born
  • Sao Jose Do Rio Preto, Brazil, 15090-000
    • Hospital de Base Da Faculdade de Medicina de
  • Sao Paulo, Brazil, 05651-901
    • Hospital Albert Einstein Sociedade Beneficente Israelita Brasileira
  • São Paulo, Brazil, 01308-050
    • Sociedade Beneficente de Senhoras Hospital Sirio Libanes
  • São Paulo, Brazil, 03102-002
    • Instituto Brasileiro de Controle do Cancer Ibcc
  • Bahia
    • Salvador, Bahia, Brazil, 41820-021
      • Centro de Oncologia Da Bahia
  • Paraná
    • Curitiba, Paraná, Brazil, 81520-060
      • Liga Paranaense de Combate ao Cancer
  • Rio De Janeiro
    • Rio De Janerio, Rio De Janeiro, Brazil, 20560-120
      • Instituto Nacional de Câncer - INCA
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-001
      • Associacao Hospitalar Moinhos de Vento Hospital Moinhos de Vento
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784-400
      • Fundacao Pio XII - Hospital de Cancer de Barretos
    • Jau/SP, São Paulo, Brazil, 17210-080
      • Hospital Dr. Amaral Carvalho/ Hospital Amaral Carvalho Jaú
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Notre Dame
    • Quebec City, Quebec, Canada, G1S4L8
      • Hospital du Saint Scarement Sacrement Laboratory
    • Rimouski, Quebec, Canada, G5L5T1
      • CSSS de Rimouski Neigette
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T1A5
      • Alan Blair Cancer Centre at Pasqua Hosptial
• France
  • Clermont-Ferrand, France, 63003
    • Centre Jean Perrin
• Germany
  • Berlin, Germany, 10713
    • Sankt Gertrauden-Krankenhaus
  • Bonn, Germany, 53111
    • Facharztpraxis fur Gynakologie und Geburtshilfe
  • Frankfurt, Germany, 60431
    • Agaplesion Markus Krankenhaus
  • Freiburg, Germany, 79110
    • Praxis für interdisziplinäre Onkologie & Hämatologie
  • Heidelberg, Germany, 69120
    • Universitaetsklinikum Heidelberg
  • Hildesheim, Germany, 31134
    • Frauenärzte am Bahnhofsplatz
  • Köln, Germany, 50679
    • Schwerpunktpraxis fur Gynakologische Onkologie
  • München, Germany, 81377
    • LMU Klinikum der Universität
  • Trier, Germany, 54290
    • Krankenanstalt Mutterhaus der Borromaerinnen
  • Ulm, Germany, 89075
    • Universitatsklinikum Ulm
• Greece
  • Athens, Greece, 11528
    • University of Athens Medical school - Regional General Hospital
  • Athens, Greece, 15562
    • IASO General
  • Faliro, Greece, 18547
    • Metropolitan Hospital
  • Heraklion, Greece, 71110
    • University General Hospital of Heraklion
  • Rio Patras, Greece, 26500
    • University General Hospital of Patras
• Italy
  • Bologna, Emilia-Romagna, Italy, 40138
    • Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
  • Ferrara, Italy, 44124
    • Azienda Ospedaliero-Universitaria di Ferrara Arcispedale Sant' Anna
  • Genova, Italy, 16132
    • IRCCS AziendaOspedaliera Universitaria San Martino
  • Grosseto, Italy, 58100
    • Presidio Ospedaliero della Misericordia
  • Messina, Italy, 98158
    • Azienda Ospedaliera Ospedali Riuniti Papardo-Piemonte
  • Monza, Italy, 20900
    • Azienda Ospedaliera San Gerardo
  • Napoli, Campania, Italy, 80131
    • Azienda Ospedaliera Universitaria Federico II
  • Napoli, Campania, Italy, 80131
    • Istituto Nazionale per lo studio e la cura dei tumori Fondazione Giovanni Pascale
  • Padova, Italy, 35128
    • Istituto Oncologico Veneto
  • Reggio Emilia, Italy, 42100
    • Arcispedale Santa Maria Nuova
  • Roma, Italy, 00189
    • Azienda Ospedaliera Sant Andrea
  • Roma, Italy, 144
    • Istituto Nazionale Tumori Regina Elena
  • Roma, Italy, 00168
    • Policlinico Universitario A Gemelli
  • Rozzano (MI), Italy, 20089
    • Istituto Clinico Humanitas
  • Torino, Piemonte, Italy, 10126
    • Azienda Ospedaliera Citta Della Salute E Della Scienza Di Torino
  • Treviglio, Italy, 24047
    • Azienda Ospedaliera Treviglio-Caravaggio
• Portugal
  • Evora, Portugal, 7000-811
    • Hospital Espirito Santo
  • Lisboa, Portugal, 1500-650
    • Hospital da Luz
  • Lisboa, Portugal, 1649-035
    • Hospital de Santa Maria
  • Porto, Portugal, 4200-072
    • Instituto Portugues de Oncologia do Porto, Francisco Gentil
• Spain
  • Barcelona, Spain, 08036
    • Clinic Barcelona Hospital Universitari
  • Barcelona, Spain, 8035
    • Hospital Universitario Vall d Hebron
  • Cordoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Madrid, Spain, 28007
    • Hospital General Gregorio Maranon
  • San Sebastian, Spain, 20014
    • Onkologikoa - Kutxaren Institutu Onkologikoa
  • Santiago de Compostela, Spain, 15706
    • Hospital Clinico Universitario de Santiago
  • Sevilla, Spain, 41071
    • Hospital Universitario Virgen Macarena
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• United Kingdom
  • Bath, United Kingdom, BA1 3NG
    • Royal United Hospital
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute UK
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Middlesex, United Kingdom, HA62RN
    • The East and North Hertfordshire NHS Trust
  • Sheffield South Yorkshire, United Kingdom, S10 2SJ
    • Sheffield Teaching Hospitals NHS Foundation Trust
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Cancer and Research Center
    • Glendale, Arizona, United States, 85306
      • Arizona Center for Cancer Care
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona
    • Scottsdale, Arizona, United States, 85251
      • Arizona Cancer Research Alliance
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
  • California
    • Anaheim, California, United States, 92801
      • Pacific Cancer Medical Center Inc
    • Escondido, California, United States, 92025
      • California Cancer Associates for Research and Excellence cCARE
    • La Jolla, California, United States, 92093
      • University of California San Diego Moores Cancer Center
    • La Verne, California, United States, 91750
      • Wilshire Oncology Medical Group, Inc
    • Los Angeles, California, United States, 90045
      • Translational Research Management
    • San Luis Obispo, California, United States, 93401
      • Coastal Integrative Cancer Care
    • Santa Maria, California, United States, 93454
      • Central Coast Medical Oncology Corporation
    • Santa Rosa, California, United States, 95403
      • Redwood Regional Medical Group, INC
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Center for Hematology-Oncology
    • Hollywood, Florida, United States, 33021
      • Memorial Breast Cancer Center
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami School of Medicine
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
    • West Palm Beach, Florida, United States, 33401
      • Florida Cancer Specialists
  • Illinois
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology-Hematology Associates, LTD
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Indiana
    • Indianapolis, Indiana, United States, 46254
      • Investigative Clinical Research of Indiana, LLC
  • Louisiana
    • Lafayette, Louisiana, United States, 70503
      • University of South Alabama Mitchell Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland School of Med
    • Bethesda, Maryland, United States, 20817
      • Center for Cancer and Blood Disorders, PC
  • Michigan
    • Detroit, Michigan, United States, 48202-268
      • Henry Ford Medical Center - New Center One
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minnesota Oncology Hematology, Pa
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • Midwest Physicians Group
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
  • New Hampshire
    • Hooksett, New Hampshire, United States, 03106
      • New Hampshire Oncology Hematology
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center Norris Cotton Cancer Center
  • New Jersey
    • Englewood, New Jersey, United States, 07631
      • Englewood Hospital and Medical Center
  • New York
    • East Syracuse, New York, United States, 13057
      • Hematology Oncology Associates of CNY
    • Lake Success, New York, United States, 11042
      • NYU Langone Arena Oncology
    • New York, New York, United States, 10021
      • Clinical Research Alliance
  • North Carolina
    • Burlington, North Carolina, United States, 27215-8700
      • Alamance Regional Medical Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnatti
    • Columbus, Ohio, United States, 43219
      • Mark H Zangmeister Center
    • Toledo, Ohio, United States, 43623
      • Toledo Community Oncology Program
  • Oklahoma
    • Lawton, Oklahoma, United States, 73505
      • Cancer Centers of Southwest Oklahoma
  • Oregon
    • Coos Bay, Oregon, United States, 97420
      • North Bend Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97213
      • Northwest Cancer Specialists, P.C. - Hoyt
  • Pennsylvania
    • Langhorne, Pennsylvania, United States, 19047
      • St Mary Medical Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee Women's Hospital
  • South Carolina
    • Columbia, South Carolina, United States, 29210
      • South Carolina Oncology Associates
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Oncology Hematology Associates
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Cancer Center
  • Texas
    • Dallas, Texas, United States, 75231
      • Texas Oncology, PA
    • Dallas, Texas, United States, 75246
      • Texas Oncology, PA- Dallas
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer and Blood Disorders
    • Houston, Texas, United States, 77030
      • UT Physicians General Medicine
    • San Antonio, Texas, United States, 78217
      • Cancer Care Centers of South Texas - Loop
    • Tyler, Texas, United States, 75702
      • Texas Oncology P.A.- Tyler
  • Virginia
    • Fredericksburg, Virginia, United States, 22408
      • Hematology Oncology Associates of Fredericksburg
    • Portsmouth, Virginia, United States, 23704
      • Delta Hematologyoncology Associates
    • Richmond, Virginia, United States, 23230
      • Virginia Cancer Institute
  • Washington
    • Spokane, Washington, United States, 99208
      • Medical Oncology Associates
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • Edwards Comprehensive Cancer Center
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital
    • Milwaukee, Wisconsin, United States, 53211
      • Columbia St Marys Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria: A subject will be eligible for inclusion in this study only if all of the following criteria are met:

1. Female subjects, age ≥ 18 years at the time informed consent is signed
2. Pathologically confirmed adenocarcinoma of the breast

3. Pathologically confirmed as triple negative, source documented, defined as both of the following

   1. Estrogen Receptor (ER) and Progesterone Receptor (PgR) negative: < 1% of tumor cell nuclei are immunoreactive in the presence of evidence that the sample can express ER or PgR (positive intrinsic controls)
   2. Human Epidermal Growth Factor Receptor 2 (HER2) negative as per American Society of Clinical Oncology - College of American Pathologists (ASCO/CAP) guidelines i. Immunohistochemistry (IHC) 0 or 1 Fluorescence In Situ Hybridization (FISH) negative (or equivalent negative test). Subjects with IHC 2 must have a negative by Fluorescence In Situ Hybridization (FISH),, (or equivalent negative test).
4. Subjects with prior breast cancer history of different phenotypes (ie, ER/PgR/HER2 positive) must have pathologic confirmation of triple negative disease in at least one of the current sites of metastasis

5. Subjects must have received prior adjuvant or neoadjuvant anthracycline therapy; unless (a) anthracycline treatment was not indicated or was not the best treatment option for the subject in the opinion of the treating physician; and (b) anthracycline treatment remains not indicated or, in the opinion of the treating physician, is not the best treatment option for the subject's metastatic disease.

   a. Newly diagnosed subjects presenting with TNMBC are eligible for the study if anthracycline treatment is not indicated or is not the best treatment option for the subject in the opinion of the treating physician.

6. Subjects with measurable metastatic disease, defined by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) guidelines
7. Life expectancy ≥ 16 weeks from randomization
8. No prior cytotoxic chemotherapy for metastatic breast cancer. Prior immunotherapy and/or monoclonal antibody therapy are acceptable. Prior treatments must have been discontinued at least 30 days prior to start of study treatment and all related toxicities must have resolved to Grade 1 or less.

9. Prior neoadjuvant or adjuvant chemotherapy, if given, must have been completed at least 6 months before randomization with all related toxicities resolved, and documented evidence of disease progression per RECIST 1.1 guidelines is required.

   a. If prior neoadjuvant or adjuvant chemotherapy contained taxane, gemcitabine, or platinum agents, the treatment must have completed at least 12 months before randomization

10. Prior radiotherapy must have completed before randomization, with full recovery from acute radiation side effects. At least one measurable lesion must be completely outside the radiation portal or there must be unequivocal radiologic or clinical exam proof of progressive disease within the radiation portal, in accordance with RECIST 1.1 guidelines
11. At least 30 days from major surgery before randomization, with full recovery
12. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

13. Subject has the following blood counts at screening:

    • Absolute Neutrophil Count (ANC) ≥ 1500/mm^2 ;
    • Platelets ≥ 100,000/mm^2 ;
    • Hemoglobin (Hgb) ≥ 9 g/dL

14. Subject has the following blood chemistry levels at screening:

    • Aspartate aminotransferase (AST) Serum glutamic-oxaloacetic transaminase (SGOT), Alanine Aminotransferase (ALT ) Serum Glutamic Pyruvate Transaminase (SGPT) ≤ 2.5 x upper limit of normal range (ULN); if hepatic metastases present ≤ 5.0 x ULN
    • Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in subjects with documented Gilbert's Syndrome
    • Creatinine clearance > 60 mL/min (by Cockcroft-Gault)

15. Females of child-bearing potential [defined as a sexually mature women who (1) have not undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months)] must:

    • Demonstrate a negative serum pregnancy test result at screening (performed by central lab) confirmed by local negative urine pregnancy dipstick within 72 hours prior to the first dose of IP); pregnancy test with sensitivity of at least 25 mIU/mL; and
    • Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, two physician approved effective contraception methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) without interruption for 28 days or longer as required by local guidelines, prior to starting study drug, during the study therapy (including dose interruptions), and for 28 days after discontinuation of the study or longer as required by local guidelines
16. Females must abstain from breastfeeding starting at randomization, during study participation and for 28 days or longer as required by local guidelines, after IP discontinuation
17. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted
18. Able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

1. Male subjects
2. Concurrent chemotherapy or any other anti tumor therapy for breast cancer. Prior immunotherapy & monoclonal antibody therapy are acceptable.
3. Subjects who received prior cytotoxic chemotherapy after incomplete resection of locoregional recurrent disease
4. History of, or known current evidence of brain metastasis, including leptomeningeal involvement.
5. Subjects with bone as the only site of metastatic disease
6. Subjects with regional lymph node as the only site of metastatic disease
7. Serious intercurrent medical or psychiatric illness, including serious active infection
8. History of class II-IV congestive heart failure or myocardial infarction within 6 months of randomization
9. History of other primary malignancy in the last 5 years prior to randomization. Subjects with prior breast cancer history are eligible, however, the most recently obtained biopsy must demonstrate triple negative disease (source documented). Subjects with prior history of in situ cancer or basal or localized squamous cell skin cancer are eligible.
10. Subjects with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple uncontrolled or unstable allergies which, in the opinion of the investigator, may lead to serious complications
11. Peripheral neuropathy Grade ≥ 2 by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
12. Subjects who have received an investigational product within the previous 4 weeks prior to randomization
13. Subject is currently enrolled, or will enroll in a different clinical study in which investigational therapeutic procedures are performed or investigational therapies are administered while participating in this study
14. Pregnant or nursing women
15. Subjects with prior hypersensitivity to nab-paclitaxel, gemcitabine, carboplatin or any other platin, or nucleoside analogue agents
16. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
17. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if she were to participate in the study
18. Any condition that confounds the ability to interpret data from the study
19. History of seropositive human immunodeficiency virus (HIV)
20. Subjects who are receiving immunosuppressive or myelosuppressive medications that would, in the opinion of the investigator, increase the risk of serious neutropenic complications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nab-Paclitaxel plus Gemcitabine; Treatment Arm A: nab-Paclitaxel 125 mg/m^2 by intravenous (IV) administration over 30 minutes, followed by gemcitabine 1000 mg/m^2 on Days 1 and 8 of each 21-day cycle by IV administration over 30 minutes	Drug: nab-Paclitaxel; nab-Paclitaxel 125 mg/m^2 by IV administration over 30 minutes on Days 1 and 8 of each 21-day treatment cycle.; Other Names: Abraxane; Drug: Gemcitabine; Gemcitabine 1000 mg/m^2 on Days 1 and 8 of each 21-day treatment cycle.; Other Names: Gemzar
Experimental: nab-Paclitaxel plus Carboplatin; Treatment Arm B: nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by IV administration followed by carboplatin at an Area Under the Curve (AUC) of 2 on Days 1 and 8 of each 21-day cycle by IV administration	Drug: nab-Paclitaxel; nab-Paclitaxel 125 mg/m^2 by IV administration over 30 minutes on Days 1 and 8 of each 21-day treatment cycle.; Other Names: Abraxane; Drug: Carboplatin; Carboplatin at an AUC of 2 on Days 1 and 8 of each 21-day cycle by IV administration; Other Names: Paraplatin AQ; Paraplatin,
Active Comparator: Gemcitabine plus Carboplatin; Treatment Arm C: Gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration followed by carboplatin AUC 2 on Days 1 and 8 of each 21-day cycle by IV administration	Drug: Gemcitabine; Gemcitabine 1000 mg/m^2 on Days 1 and 8 of each 21-day treatment cycle.; Other Names: Gemzar; Drug: Carboplatin; Carboplatin at an AUC of 2 on Days 1 and 8 of each 21-day cycle by IV administration; Other Names: Paraplatin AQ; Paraplatin,

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kaplan-Meier Estimates of Progression-Free Survival (PFS) Based on Investigator Assessment.	PFS was defined as the time from the date of randomization to the date of disease progression or death from any cause on or prior to the data cutoff date for the statistical analysis, whichever occurred earlier. Tumor responses were assessed every 6 weeks using, Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and defined as: Complete response (CR) is the disappearance of all target lesions; Partial response (PR) occurs when at least a 30% decrease in the sum of diameters of target lesions from baseline; Stable disease is neither sufficient shrinkage to qualify for a PR nor sufficient increase of lesions to qualify for Progressive disease (PD); Progressive Disease- is at least a 20% increase in the sum of diameters of target lesions from nadir.	From date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With an Objective Complete or Partial Overall Response by Investigator Assessment.	Percentage of participants with an Objective Complete or Partial Overall Response according to RECIST 1.1 and defined as: Complete response-disappearance of all target lesions; partial response at least a 30% decrease in the sum of diameters of target lesions from baseline; stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for Progressive disease (PD)• Progressive Disease- At least a 20% increase in the sum of diameters of target lesions from nadir.	Disease response was assessed every 6 weeks; from date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C
Percentage of Participants Who Initiated Cycle 6 Receiving Doublet Combination Therapy	The percentage of participants who initiated Cycle 6 receiving doublet combination therapy regardless of the need for dose modifications.	Cycle 6
Kaplan-Meier Estimates of Overall Survival	Overall survival was defined as the time from the date of randomization to the date of death (from any cause).	From date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	Treatment-emergent adverse events (TEAEs) were defined as any AEs that began or worsened with the onset date on or after the date of the first dose of IP through 28 days after the last dose. A serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was graded based on the participant's symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity as follows: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death.	From randomization through to 28 days after the last dose of IP; up to data cut off date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C
Percentage of Participants Experiencing Dose Modifications (Reductions and Interruptions)	The number of participants with dose modifications occurring during the treatment period. Dose reductions and interruptions are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.	From randomization through to 28 days after the last dose of IP; up to data-cut off of date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C
Percentage of Participants Who Discontinued From All Study Treatment Due to TEAEs	Treatment-emergent adverse events (TEAEs) were defined as any AEs that begin or worsen with an onset date on or after the date of the first dose of IP through 28 days after the last dose.	From randomization through to 28 days after the last dose of IP; up to data-cut off of date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Ileana Elias, M.D., Celgene Corporation

Publications and helpful links

General Publications

• Yardley DA, Brufsky A, Coleman RE, Conte PF, Cortes J, Gluck S, Nabholtz JM, O'Shaughnessy J, Beck RM, Ko A, Renschler MF, Barton D, Harbeck N. Phase II/III weekly nab-paclitaxel plus gemcitabine or carboplatin versus gemcitabine/carboplatin as first-line treatment of patients with metastatic triple-negative breast cancer (the tnAcity study): study protocol for a randomized controlled trial. Trials. 2015 Dec 16;16:575. doi: 10.1186/s13063-015-1101-7. Erratum In: Trials. 2016;17:63.
• Liu MC, Janni W, Georgoulias V, Yardley DA, Harbeck N, Wei X, McGovern D, Beck R. First-Line Doublet Chemotherapy for Metastatic Triple-Negative Breast Cancer: Circulating Tumor Cell Analysis of the tnAcity Trial. Cancer Manag Res. 2019 Dec 12;11:10427-10433. doi: 10.2147/CMAR.S208712. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2013
• Primary Completion (Actual): October 28, 2016
• Study Completion (Actual): October 28, 2016

Study Registration Dates

• First Submitted: June 17, 2013
• First Submitted That Met QC Criteria: June 17, 2013
• First Posted (Estimate): June 19, 2013

Study Record Updates

• Last Update Posted (Actual): February 21, 2019
• Last Update Submitted That Met QC Criteria: February 19, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Breast Cancer; carboplatin; Gemzar; gemcitabine; Triple Negative Breast Cancer; Cancer of the Breast; Metastatic Breast Cancer; Abraxane; Phase 3; Phase 2; nab-Paclitaxel; Paraplatin; Estrogen receptor negative breast cancer; Metastatic Triple Negative Breast Cancer; ABI-007; HER2 Negative Breast Cancer; Triple Negative Metastatic Breast Cancer; Basal-like breast cancer; Hormone receptor negative breast cancer; Progesterone negative receptor breast cancer; Paraplatin AQ
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Gemcitabine; Carboplatin; Paclitaxel
• Other Study ID Numbers: ABI-007-MBC-001; 2013-000113-20 (EudraCT Number)