Abstract OT2-05-01: A phase II randomized trial of gemcitabine plus cisplatin(GP) vs. gemcitabine plus carboplatin (GC) as the first-line treatment for patients with metastatic triple negative breast cancer
Authors: Gong C , Cao E , Wang Z , Zhang J , Wang L , Cao J , Zhang S , Tao Z , Li T , Zhao Y , Li Y , Wang B , Hu X 
Published: February 2018

Background:

Triple-negative breast cancer (TNBC) is an aggressive disease with limited treatment options and poor prognosis. Gemcitabine plus carboplatin (GC) is one of the preferred chemotherapeutic regimens for patients with metastatic triple-negative breast cancer(mTNBC), with a median progression-free survival(PFS) of 4.6 months in the first-line patients (O'Shaughnessy J, et al. J Clin Oncol 2014). Gemcitabine plus cisplatin (GP) has also demonstrated promising efficacy and safety in the first-line phase III trial of mTNBC, with a median PFS of 7.7 months (Hu XC, Lancet Oncol 2015). A recent analysis, based on data derived from a cohort of 379 mTNBC patients, indicated that patients receiving cisplatin-based regimen as the first-line chemotherapy showed better PFS compared with other platinum agents (8.0 vs 4.3 months, P = 0.03) (Zhang J, et al. Oncotarget 2015). To further investigate the superiority between carboplatin and cisplatin when combined with gemcitabine, this phase II study was conducted to directly compare the efficacy and safety of GP with GC in the first-line treatment for patients with metastatic triple negative breast cancer.

Trial Design:

This prospective phase II, single center, open-label, randomized study has been designed to compare the efficacy and safety of GP with GC as the first-line treatment for mTNBC. Patients are randomized 1:1 to receive gemcitabine (1250 mg/m2, D1,8) plus cisplatin (75 mg/m2, D1) or gemcitabine (1000mg/m2, D1,8) plus carboplatin (area under the curve 2 mg × min/mL, D1,8) every 21 days until disease progression or intolerable toxicity.

Eligibility Criteria:

Patients with histologically confirmed triple negative metastatic breast cancer, with no prior chemotherapy in metastatic setting will be included in this trial. Eligible patients must be between 18 and 70 years of age with a performance status of 0–1, adequate organ function and at least one RECIST 1.1-measurable lesion.

Specific Aims:

The primary endpoint is PFS. Secondary endpoints include objective response rate, safety and overall survival.

Statistical Methods:

The sample size of the present study was determined based on the results of two phase III clinical trials: the median PFS for patients receiving GC and GP as the first-line treatment for mTNBC was 4.6 and 7.7 months, respectively. This design was hypothesized that GP would be superior to GC in terms of efficacy. Thus, in order to detect an improvement of median PFS from 4.6 months to 7.7 months, with 80% power and a 1-sided type I error of 0.05, 136 patients would be required. Considering a drop-out rate of 10%, a total of 150 patients planned to be enrolled.

Present Accrual and Target Accrual:

Target accrual: 150. Present accrual (2017/5/24): 83

Contact information: Contact: Xichun Hu, MD, PHD xchu2009@hotmail.com

Biyun Wang, MD pro_wangbiyun@163.com

ClinicalTrials.gov Identifier: NCT02341911.

Citation Format: Gong C, Cao E, Wang Z, Zhang J, Wang L, Cao J, Zhang S, Tao Z, Li T, Zhao Y, Li Y, Wang B, Hu X. A phase II randomized trial of gemcitabine plus cisplatin(GP) vs. gemcitabine plus carboplatin (GC) as the first-line treatment for patients with metastatic triple negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-05-01.