Abstract OT2-2-01: tnAcity: A phase II/III trial of nab-paclitaxel (nab-P) plus either gemcitabine (Gem) or carboplatin (Carbo) vs Gem/Carbo as first-line treatment for patients with triple-negative metastatic breast cancer (TNMBC)
Authors: Yardley Denise A , Coleman Robert E , Conte Pierfranco , O'Shaughnessy Joyce , Cortes Javier , Glück Stefan , Brufsky Adam , Nabholtz Jean-Marc A , Li Li , Miller JulieAnn , Barton Debora , Harbeck Nadia 
Published: May 2015

Abstract
Background: TNMBC has an aggressive clinical course and poor prognosis. In phase II trials, nab-P–based therapy has demonstrated efficacy and tolerability as first-line therapy, in patients with MBC. The international triple-negative Albumin-bound paclitaxel combination treatment study (tnAcity) will evaluate 2 nab-P regimens (with either Gem or Carbo) and compare the selected regimen with Gem/Carbo as first-line treatment for TNMBC.
Trial design: All patients must have pathologically confirmed TNBC (TN defined as &lt; 1% estrogen receptor and progesterone receptor expression by immunohistochemistry (IHC) and 0 - 1+ human epidermal growth factor receptor 2 expression by IHC or confirmed negative by fluorescence in situ hybridization) with measurable metastatic disease. Eligibility criteria include no prior cytotoxic therapy for MBC, prior adjuvant or neoadjuvant anthracycline use unless not indicated by physician or other appropriate regimens were administered, and no history or current evidence of brain metastasis. Prior neoadjuvant or adjuvant chemotherapy must have been completed ≥ 6 months before randomization (≥ 12 months if using taxane-, Gem-, or platinum-containing regimen). Patients will be enrolled internationally in North America, Europe, Latin America, and Australia. In the phase II portion, 240 patients will be randomized to receive nab-P 125 mg/m2 plus Gem 1000 mg/m2 (arm A), nab-P 125 mg/m2 plus Carbo area under the curve (AUC) 2 (arm B), or the control regimen of Gem 1000 mg/m2 plus Carbo AUC 2 (arm C), all given intravenously on days 1 and 8 of a 21-day cycle. The phase II portion will identify the nab-P combination to be evaluated in the phase III portion based on efficacy and safety (Table 1). In the phase III portion, 550 patients will receive the selected nab-P regimen (A or B) or Gem/Carbo. The primary endpoint of the phase III portion is progression-free survival (PFS) by independent radiological assessment; secondary endpoints include overall response rate (ORR), overall survival (OS), disease control rate, duration of response, and safety (Table 1). Monotherapy is allowed in the event of hypersensitivity or toxicity to 1 of the treatment components. The trial design provides ≈ 90% power to detect a hazard ratio of 0.70 for PFS with a 2-sided 5% significant level. Current enrollment is 52 patients. Clinical trial NCT01881230.
Trial Design
ParameterPhase IIPhase IIINn = 240n = 550Randomization1:1:11:1StratificationDisease-free interval (DFI): ≤ 1 y vs &gt; 1 yDFI: ≤ 1 y vs &gt; 1 y Prior neo/adjuvant taxane (yes vs no)Key EndpointsPrimaryPFS by investigator assessmentPFS by independent assessment SecondaryORR by investigator assessmentORR Percentage of patients to initiate cycle 6OS OSPFS by investigator assessment SafetyDisease control rate Duration of response Safety ExploratoryTime to second-line therapy or deathTime to second-line therapy or death Circulating tumor cellsQuality of life Tumor biomarkersHealthcare resource utilization Tumor biomarkers
Citation Format: Denise A Yardley, Robert E Coleman, Pierfranco Conte, Joyce O'Shaughnessy, Javier Cortes, Stefan Glück, Adam Brufsky, Jean-Marc A Nabholtz, Li Li, JulieAnn Miller, Debora Barton, Nadia Harbeck, on bahalf of the tnAcity Investigators. tnAcity: A phase II/III trial of nab-paclitaxel (nab-P) plus either gemcitabine (Gem) or carboplatin (Carbo) vs Gem/Carbo as first-line treatment for patients with triple-negative metastatic breast cancer (TNMBC) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT2-2-01.