Background: Cancer patients receiving taxane-based chemotherapy develop alopecia, which may lead to significant psychosocial, quality of life, and adherence issues. Besides a recently FDA-cleared scalp cooling device, there are no oral/ topical agents available prevent CIA. In murine studies, topical calcitriol reduced CIA, likely due to arrest of cell cycle in healthy hair follicles, and reduction in the sensitivity of follicular epithelium to chemotherapy. Methods: Up to 31 adult women with cancer (breast, gynecologic, soft-tissue/bone sarcoma) applied 1mL of BPM31543 to scalp bid, ≥ 5 days prior to initiation of taxane-based chemotherapy until 3 months or end of chemotherapy, in this dose-escalation study (5/10/20/40/60/80μg/mL cohorts). Periodic PK analysis, adverse event (AE) monitoring, patient self-assessment diaries (1-10 scale), and blinded photographic assessments were done. Results: Twenty-one subjects have been enrolled so far (evaluable, n = 13). PK data (n = 16; 5-40μg/mL) showed inter-individual variability, but no significant dose-dependent increase in systemic absorption (range, < 20-110 pg/mL). Treatment-related AEs (probably/possibly) were mild/moderate, and included scalp pain (n = 1; 5 μg/mL), elevated vitamin D levels in 1 patient (20μg/mL) and with passage of renal calculus in another (n = 1; 40μg/mL). All subjects reported changes in overall fullness, thickness, and volume of hair during chemotherapy, and experienced hair loss, with 85% showing a ≥ 75% increase in their rating (maximum, week 4) at the 5/10 μg/mL dose level. At the ≥ 20 μg/mL dose level, ≥ 75% hair loss was seen only in 43%. Hair loss/ thinning caused all subjects to change their hair style (onset, week 2; peak, weeks 5-6). Conclusions: Topical BPM31543 is safe and tolerable with potential activity at higher dosing levels. Clinical trial information: NCT01588522