Abstract P5-11-11: A phase I safety study of topical calcitriol (BPM31543) for the prevention of chemotherapy-induced alopecia (CIA)

Abstract

Abstract Background: Chemotherapy induced alopecia (CIA) may lead to significant psychosocial and quality of life issues. Currently there are no FDA approved oral or topical agents available to prevent CIA. In murine studies, topical calcitriol reduced CIA, due to arrest of cell cycle in healthy hair follicles, and reduction in the sensitivity of follicular epithelium to chemotherapy. Methods: A prospective dose escalation study is being performed in up to 31 women with breast cancer, gynecologic cancer and sarcomas. Each patient is applying 1mL of BPM31543 to her scalp bid, ≥ 5 days prior to initiation of taxane-based chemotherapy for at least 3 months or until the completion of chemotherapy. The study cohorts are: 5/10/20/40/60/80μg/mL. The first 5 cohorts are completely enrolled and the final cohort is currently being enrolled. Each patient undergoes pk analysis, adverse event (AE) monitoring, patient self-assessment diaries (1-10 scale), and blinded photographic assessments. Efficacy and pK data are still being collected and analyzed for the patients on study, but will be available by December. Results: Twenty-four subjects have been enrolled so far (evaluable at this time, 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 in nature and included scalp pain (n = 1; 5 μg/mL), elevated vitamin D levels in 1 patient (20μg/mL) and passage of renal calculus in another (n = 1; 40μg/mL). All subjects reported changes in overall hair fullness, thickness, and volume of hair during chemotherapy. At the 5/10 μg/mL dose level, ≥ 75% hair loss was reported in 85% of patients. At the ≥ 20 μg/mL dose level, ≥ 75% hair loss was seen only in 43% of patients. Hair loss/ thinning caused all subjects to change their hair style (onset, week 2; peak, weeks 5-6). Conclusions: Data have shown that the twice daily application of BPM31543 in patients receiving taxane-based chemotherapy was safe and well-tolerated. Efficacy data from the preliminary analysis was promising and led to the amendment of the study to evaluate two additional higher dose cohorts: 60 and 80 μg/ml. Citation Format: Goldfarb SB, Konner J, Stevens J, Brouwer S, Narain NR, Ye R, Ravipaty S, Sarangarajan R, Akmaev VR, Jimenez JJ, Belum VR, 'Kitts S, Ciccolini K, Berman B, Lacouture ME. A phase I safety study of topical calcitriol (BPM31543) for the prevention of chemotherapy-induced alopecia (CIA) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-11-11.