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

BackgroundTriple-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.Trial designIn 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.MethodsIn 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.DiscussionThe tnAcity trial aims to identify a new standard cytotoxic chemotherapy regimen for first-line treatment of metastatic triple-negative breast cancer.Trial registrationClinicalTrials.gov: NCT01881230. Date of registration: 17 June 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-1101-7) contains supplementary material, which is available to authorized users.

Addition of gemcitabine to paclitaxel, epirubicin, and cyclophosphamide adjuvant chemotherapy for women with early-stage breast cancer (tAnGo): final 10-year follow-up of an open-label, randomised, phase 3 trial

“…Gemcitabine has recently been included in an international trial in metastatic TNBC with carboplatin and nab-paclitaxel 19,20 [HE1]. The first results of the Phase 2 feasibility study were presented at the San Antonio Breast Cancer Symposium in December 2016 [20], and showed no benefit from the addition of gemcitabine.…”

Mammalian target of rapamycin inhibitor RAD001 sensitizes endometrial cancer cells to paclitaxel-induced apoptosis via the induction of autophagy

“…Paclitaxel is a common anticancer drug that is used in combination chemotherapy (29–32). Although a high dose of paclitaxel has proven to be more effective, its clinical toxicity is severe (33,34).…”

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“…TNMBC is generally composed of heterogeneous group of cancers with high rate of proliferation and poorly differentiated cells [68]. Patients with TNBC present early disease recurrence, and reduced survival rate compared with other BCs [68].…”

“…TNMBC is generally composed of heterogeneous group of cancers with high rate of proliferation and poorly differentiated cells [68]. Patients with TNBC present early disease recurrence, and reduced survival rate compared with other BCs [68]. This type of BC is characterized by the lack of both estrogen and progesterone receptors (ER and PR), and lack of human epidermal growth factor 2 (Her2) [66], which limits the treatment options for females affected with it [66].…”

“…Results of the study indicated that the use of platinum agent plus taxane regimen produced grater efficacy than capecitabine regimen, with improved ORR, OS and progression-free survival (PFS) [74]. However, there is a limitation in the availability of optimal care of regimen for TNMBC patients [68]. Hence, the lack of established molecular targets therapy and poor prognosis are still major obstacles for TNMBC patients and oncologists [75].…”