CTNI-52. PHASE I STUDY OF WHOLE BRAIN RADIOTHERAPY WITH CONCOMITANT ERIBULIN FOR ADVANCED BREAST CANCER BRAIN METASTASIS

Abstract Whole-brain irradiation (WBI) is performed for patients with progressive metastatic breast cancer brain tumors who are not candidates for surgery or stereotactic radiosurgery/radiotherapy (SRS/SRT). While WBI is an established safe treatment, it is positioned as a palliative treatment. Eribulin, a microtubule inhibitor, is approved for recurrent breast cancer and arrests tumor cells in the M phase of the cell cycle, which is known to be most radiosensitive. We have previously reported that eribulin has a radiosensitizing effect in a glioblastoma mouse model. Although single-agent eribulin did not meet the primary endpoint in a Phase II study (UMIN000030359) for recurrent glioblastoma patients, its safety was confirmed. The combination may extend the duration of lesion control which leads to prolonged overall survival. Therefore, we planned a Phase I clinical trial to confirm the safety of this treatment. This clinical trial is a single-arm, two-institution phase I clinical study. The main eligibility criteria for enrolled patients include progressive metastatic breast cancer brain tumors indicated for WBI, and even if there is a history of SRS/SRT, eligibility can be determined by the radiation oncologist. Eribulin administration will be administered intravenously once a week for two consecutive weeks, followed by 1-week intervals, 3 weeks in total as one cycle. Radiation therapy is fixed at 2.5 Gy x 15 fractions, while the eribulin dose will start at a 70% reduced dose of 1.1 mg/m² using a 3 + 3 design, with three cohorts set at 0.7, 1.1, and 1.4 mg/m². The primary endpoint is DLT (dose-limiting toxicity, defined as criteria for discontinuing single-agent eribulin and side effects presumed to be associated with radiation therapy) before the start of the second cycle. Secondary endpoints include overall survival, progression-free survival, response rate, and MMSE. This study is recently enrolling in Japan (jRCT1031250065).