title: 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.
abstract: BACKGROUND
  Triple-negative breast cancer is an aggressive disease with unmet clinical needs. In a phase III study of patients with metastatic triple-negative breast cancer, first-line gemcitabine/carboplatin resulted in a median progression-free survival of 4.6 months. nab-paclitaxel-based regimens (with gemcitabine or carboplatin±bevacizumab) also demonstrated efficacy and safety in first-line phase II trials of human epidermal growth factor receptor 2-negative metastatic breast cancer.
  
  
  METHODS
  In this international, multicenter, open-label, randomized phase II/III trial, the efficacy and safety of first-line nab-paclitaxel with gemcitabine or with carboplatin will be compared with gemcitabine/carboplatin (control arm) for metastatic triple-negative breast cancer.
  
  
  METHODS
  In the phase II portion, 240 patients with measurable metastatic triple-negative breast cancer and treatment-naive for metastatic disease will be randomized 1:1:1 (stratified by disease-free interval: ≤1 versus>1 year) to nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2, nab-paclitaxel 125 mg/m2 plus carboplatin area under the curve 2 mg×min/mL, or gemcitabine 1000 mg/m2 plus carboplatin area under the curve 2 mg×min/mL, all given on days 1 and 8 of a 21-day cycle. Investigator-assessed progression-free survival (primary endpoint), overall response rate, overall survival, and safety will be assessed. A ranking algorithm of five efficacy and safety parameters will be used to pick the "winner" of the nab-paclitaxel regimens. In the phase III portion, 550 patients will be randomized 1:1 (stratified by disease-free interval: ≤1 versus >1 year, and prior adjuvant/neoadjuvant taxane use) to the nab-paclitaxel combination arm selected from the phase II portion or to the control arm. Patients in phase II will not be part of the phase III population. The phase III primary endpoint is blinded, independently-assessed progression-free survival; secondary endpoints include blinded, independently-assessed overall response rate, overall survival, disease control rate, duration of response, and safety. Biomarker and circulating tumor-cell exploratory analyses and quality-of-life assessments will also be performed. A list of approving ethical bodies was provided in Additional file 1.
  
  
  CONCLUSIONS
  The tnAcity trial aims to identify a new standard cytotoxic chemotherapy regimen for first-line treatment of metastatic triple-negative breast cancer.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01881230 . Date of registration: 17 June 2013.
authors.affiliation: Sarah Cannon Research Institute and the Tennessee Oncology, PLLC, 250 25th Avenue North, Suite 100, Nashville, TN, 37203, USA. dyardley@tnonc.com.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA, USA. brufskyam@upmc.edu.
authors.forename: Adam
authors.initials: A
authors.lastname: Brufsky
authors.affiliation: Weston Park Hospital, Sheffield Cancer Research Center, Sheffield, England. r.e.coleman@sheffield.ac.uk.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Coleman
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, and Istituto Oncologico Veneto IRCCS, Padova, Italy. pierfranco.conte@unipd.it.
authors.forename: Pierfranco F
authors.initials: PF
authors.lastname: Conte
authors.affiliation: Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. jacortes@vhio.net.
authors.forename: Javier
authors.initials: J
authors.lastname: Cortes
authors.affiliation: Celgene Corporation, Summit, NJ, USA. sgluck@celgene.com.
authors.forename: Stefan
authors.initials: S
authors.lastname: Glück
authors.affiliation: Centre de Lutte Contre le Cancer d'Auvergne, Clermont Ferrand, France. Jean-Marc.NABHOLTZ@cjp.fr.
authors.forename: Jean-Mark A
authors.initials: JM
authors.lastname: Nabholtz
authors.affiliation: Texas Oncology-Baylor Charles A. Sammons Center; US Oncology, Dallas, TX, USA. Joyce.OShaughnessy@USONCOLOGY.COM.
authors.forename: Joyce
authors.initials: J
authors.lastname: O'Shaughnessy
authors.affiliation: Celgene Corporation, Summit, NJ, USA. rbeck@celgene.com.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Beck
authors.affiliation: Celgene Corporation, Summit, NJ, USA. ako@celgene.com.
authors.forename: Amy
authors.initials: A
authors.lastname: Ko
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: Markus F
authors.initials: MF
authors.lastname: Renschler
authors.affiliation: Celgene Corporation, Summit, NJ, USA. dbarton@celgene.com.
authors.forename: Debora
authors.initials: D
authors.lastname: Barton
authors.affiliation: Breast Center, University of Munich, Munich, Germany. Nadia.Harbeck@med.uni-muenchen.de.
authors.forename: Nadia
authors.initials: N
authors.lastname: Harbeck
mesh_terms: D000418:Albumins / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D002985:Clinical Protocols; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D012107:Research Design; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000093542:Gemcitabine
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine