Preoperative Parpi and Irradiation (popi) for Women with an Incomplete Response to Neoadjuvant Chemotherapy (nac) for Breast Cancer: A Phase I Trial.

TPS1142 Background: Fifty to seventy percent of breast cancer patients treated with NAC will have an incomplete response and ultimately worse outcomes than those with a pathologically complete response (pCR). Researchers hoping to increase the rate of pCR, added pre-operative radiation to NAC but had little success. One way to further increase the response to neoadjuvant radiation may be the concurrent use of an inhibitor of Poly(ADP-ribose)-polymerase (PARPi). Pre-clinical studies have shown that PARPi sensitizes cancer cells to radiation by inhibiting repair of radiation-induced ssDNA breaks. We hypothesize that POPI will increase the pCR rate in women who have residual disease after NAC. Before we can test this hypothesis, we must determine the max tolerable dose (MTD) of this combined therapy. Thus, we designed and opened a phase I trial of POPI in women with an incomplete response to NAC. Methods: Women with pathologically node positive disease before NAC and > 1.0 cm of residual disease after NAC are eligible. After obtaining consent the residual disease is biopsied. Patients with viable disease are enrolled in a standard 3+3 dose finding study of concurrent veliparib and pre-operative radiation. The starting dose of veliparib is 50 mg P.O. BID x 28 days and will increase by 50mg BID to a max of 200 mg BID. Radiation (235 cGy x 16) to the breast and regional nodes overlaps with the first 3 weeks of veliparib. Definitive surgery (lumpectomy/mastectomy) occurs 6 weeks after completion of radiation. The MTD is defined as the dose below the level at which >1dose limiting toxicity (DLT) is observed in 3-6 patients. An expansion cohort of 20 patients will be treated at the MTD for further evaluation. Status: This trial opened in 8/2013. Two patients have completed protocol therapy to date. Clinical trial information: NCT01618357.