Study design and treatments
This was a single-institution study with a dose escalation (phase 1) and expansion (phase 2) part (Fig. Study Schema and Pharmacokinetics. Letrozole was continued until the day prior to surgery. For everolimus and carotuximab, an interval of 4 weeks between last dose and surgery was required. The first dose of carotuximab was split into two infusions, each administered over 4 h, on days 1 (3 mg/kg) and 4 (12 mg/kg or 7 mg/kg if dose de-escalation occurred). If well tolerated, all subsequent infusions were administered as a whole every 2 weeks; infusion time was step-wise reduced to a minimum of 90 min. Premedications for each infusion included acetaminophen 650 mg PO, methylprednisolone 100 mg IV, famotidine 20 mg and cetirizine 10 mg PO or IV.Delays for up to 3, 7, 7, and 14 days for goserelin, letrozole, everolimus, and carotuximab, respectively, were allowed. If carotuximab were delayed for > 3 days, the first dose of carotuximab upon resumption had to be split into two doses: 3 mg/kg on day 1 and the remainder on day 4. Dose reductions down to 2.5 mg PO daily and 10 mg/kg q 2 weeks were allowed for everolimus and carotuximab, respectively.