412TiP - 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 f...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Presenter Pier Franco Conte
Citation Annals of Oncology (2014) 25 (suppl_4): iv116-iv136. 10.1093/annonc/mdu329
Authors P.F. Conte1, D.A. Yardley2, A. Brufsky3, R.E. Coleman4, J. Cortes5, S. Gluck6, J. Nabholtz7, J. O’shaughnessy8, L. Li9, J. Miller10, D. Barton10, N. Harbeck11
  • 1Surgery, Oncology, And Gastroenterology, University of Padova, 35128 - Padova/IT
  • 2Medical Oncology, Sarah Cannon Research Institute, Tennessee Oncology, PLLC, Nashville/US
  • 3Oncology, University of Pittsburgh Medical Center, Pittsburgh/US
  • 4Academic Unit Of Clinical Oncology, Weston Park Hospital,Sheffield Cancer Research Centre, 2SJ - Sheffield/GB
  • 5Oncology, University Hospital Vall d'Hebron, Barcelona/ES
  • 6Hematology/oncology, University of Miami, Miami/US
  • 7Oncology, Centre de Lutte Contre le Cancer d’Auvergne, Clermont Ferrand/FR
  • 8Medical Oncology, US Oncology, Dallas/US
  • 9Biometrics And Data Operations, Celgene Corporation, Summit/US
  • 10Clinical Research, Celgene Corporation, Summit/US
  • 11Breast Center, University of Munich, Munich/DE

Abstract

Background

TNMBC is an aggressive BC subtype with few treatment options. Phase II trials have demonstrated efficacy and tolerability of nab-P–containing regimens for TNMBC. The international triple-negative Albumin-bound paclitaxel combination treatment study (tnAcity) will examine 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 TNMBC (TN defined as ER and PgR expression < 1% by IHC and HER2 0 - 1+ by IHC or confirmed negative by FISH). Pts will be enrolled in North America, Europe, Latin America, and Australia. In the phase II portion, 240 pts will 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. Eligibility criteria include no prior cytotoxic therapy for MBC, prior adjuvant or neoadjuvant anthracycline use unless not indicated, and no history or current evidence of brain metastasis. Adjuvant taxane-, Gem-, or platinum-containing regimens must have been completed ≥ 12 mo before randomization (6 mo for all others). The phase II portion will identify the nab-P combination to be evaluated in the phase III portion based on efficacy and safety. In the phase III portion, 550 pts will receive the selected nab-P regimen (A or B) or Gem/Carbo. The trial design provides ≈ 90% power to detect a hazard ratio of 0.70 for progression-free survival (PFS).

Previous publication: SABCS 2013 [OT3-1-11]

Trial Design

Parameter Ph II Ph III
Randomization 1:1:1 1:1
Stratification - Disease-free interval (DFI): ≤ 1 y vs > 1 y - DFI: ≤ 1 y vs > 1 y - Prior neo/adjuvant taxane
Key Endpoints
Primary PFS by investigator assessment PFS by independent assessment
Secondary - Overall response rate (ORR) - % pts to initiate cycle 6 - Overall survival (OS) - Safety - ORR - OS - Disease control rate - Duration of response - Safety
Exploratory - Time to 2nd-line therapy or death - Circulating tumor cells - Tumor biomarkers - Time to 2nd-line therapy or death - Quality of life - Healthcare resource utilization

Disclosure

J. Cortes: Consultant or advisory role (Novartis, Celgene, Roche), Honoraria (Novartis, Celgene, Roche, Eisai); S. Gluck: Consulting fees (Agendia, Genomic Health, Celgene, Eisai, Genentech, Dara), contracted research (Agendia, Genomic Health, Celgene, Eisai, Genentech, Dara); J. O'shaughnessy: Consulting fees (Genentech, Sanofi US, Boehringer Ingelheim Int GmbH, BMS, Caris Diagnostics, Eisai, GSK, J&J, Roche), fees for non-CME services (BMS, Celgene, Eisai, Genentech); L. Li, J. Miller and D. Barton: Employee and stock ownership (Celgene); N. Harbeck: Consulting fees (Celgene). All other authors have declared no conflicts of interest.