A Phase I, Multicenter, Open-Label, Two-Part, Dose-Escalation Study of RAD1901 in Postmenopasual Women With Advanced Estrogen Receptor Positive and HER2-Negative Breast Cancer (CTMS# 15-2042)
There are two parts to this Phase I study; the first part of the study (Dose Escalation, Part A) is designed to determine the MTD of RAD1901 in postmenopausal women with advanced breast cancer who are ER positive and HER2 negative. The second part of this study (Safety Expansion, Part B) is to evaluate the safety, tolerability and preliminary efficacy of therecommended Phase 2 dose (RP2D).RAD1901 will be administered orally on a continuous daily dosing schedule. The study consists of a dose escalation (Part A) followed by a safety expansion (Part B), as described below.Part A, Dose Escalation:Patients will be assigned sequentially to escalating doses of RAD1901 using a standard 3+3 design. At each dose level, a cohort of at least 3 evaluable patients will typically be treated. The decision to dose escalate will be determined by the Study Committee (SC). The starting dose will be 200 mg administered orally once daily. Dosing will be escalated inincrements of 200 mg for each new cohort of patients. It is estimated that 5 cohorts will be required to determine the MTD (i.e. 200 mg, 400 mg, 600 mg, 800 mg, 1000 mg). The MTD is defined as the highest dose at which 0/3, 0/6 or 1/6 patients experience a dose limiting toxicity (DLT) during the first 28 days of treatment. For the purposes of dose escalation decisions, the DLT evaluation period will be Day 1 through Day 28.Part B, Safety Expansion:Once the MTD has been identified and/or a RP2D has been selected in the dose escalation part of the study, additional patients will be enrolled to the safety expansion part in order to further evaluate the safety, tolerability and preliminary efficacy of the RP2D.