Abstract OT2-2-02: Phase I/II clinical trial on the combination of carboplatin, eribulin and E7449

Abstract

Abstract The combination of carboplatin and eribulin has been found to be effective in triple negative breast cancer patients. A recently conducted neoadjuvant clinical trial showed a pathologic complete response (pCR) of 45% with four cycle of carboplatin and eribulin. Recent preclinical data from EISAI suggest that there is synergy between carboplatin, eribulin and E7449 (an oral PARP inhibitor) in BRCA deficient and PTEN mutated xenograft models. Loss of Heterozygosity (LOH) is DNA alterations which develop through double strand DNA breaks. The homologous recombination (HRD) Score is calculated by the number of LOH regions greater 15Mb in length and less than an entire chromosome present in the genome. A high HRD score is present in BRCA deficient tumors and predicts for sensitivity to platinum-based chemotherapy. We propose a phase I/II clinical trial on the combination of carboplatin, eribulin and E7449. As part of the phase I clinical trial HRD will be performed and correlated to response to therapy. In the phase II clinical trial women with BRCA related breast or ovarian cancer, triple negative breast or ovarian cancer with high HRD score or PTEN deficient will be enrolled at a dose level found during the phase I clinical trial. Tissue will be requested to test for PARP inhibition. The primary endpoint of the phase II clinical trial is response rate. A total of 30 patients will be enrolled to the phase II clinical trial. Citation Format: Virginia Kaklamani, Ruth o'Regan, Kari Wisinski, Kent Hoskins, James Wade, William Gradishar. Phase I/II clinical trial on the combination of carboplatin, eribulin and E7449 [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 OT2-2-02.