Phase II neoadjuvant trial with carboplatin and eribulin mesylate in patients with triple-negative breast cancer.

Abstract

TPS1134 Background: Several neoadjuvant trials have been conducted in triple negative breast cancer (TNBC) with platinum agents with pathologic complete response (pCR) ranging from 16%-32%. Eribulin mesylate, a nontaxane microtubule dynamics inhibitor, has clinical activity as monotherapy in breast cancer and other solid tumors. A recent phase I trial found the combination of eribulin mesylate with carboplatin was well tolerated and showed activity in advanced solid tumors. The recommended dose for future trials was eribulin mesylate 1.1 mg/m2 and carboplatin AUC6. We proposed a neoadjuvant phase II trial with the combination of carboplatin and eribulin in patients with TNBC. Methods: This is a non-randomized, open-label, multi-center, phase II clinical trial of eribulin and carboplatin enrolling histologically-confirmed TNBC patients. Our primary endpoint is to determine the pCR in TNBC patients treated with the combination of carboplatin and eribulin. Secondary endpoints include determination of the clinical response rate, toxicity evaluation and measurement of stem cell and TLE3 as a biomarker of response to eribulin therapy. To obtain an alpha of 0.10 and a power of 0.90, a sample size of 30 patients is required to detect a pCR rate >=30%. 10 of the planned 30 patients have been enrolled to date. Treatment will be given every 3 weeks for a total of 4 cycles of therapy. There will be an initial safety run-in to evaluate the appropriate dose of eribulin in this population. The first 10 patients will receive eribulin at 1.4 mg/m2 (intravenously over 2-5 minutes) followed by carboplatin AUC=6 (intravenously over 30 minutes). After the 10th patient has been enrolled, the study will be temporarily suspended pending review; toxicity will be assessed for these first 10 patients (cycle 1 only) to assess whether this dose of eribulin will be used for the remaining patients or if a reduction to a dose of 1.1 mg/m2 will be required. Definitive surgery will be performed 3-8 weeks after completion of therapy, which will conclude the duration of the study. Clinical Trial Registry Number NCT01372579.