A phase I safety study of topical calcitriol (BPM31543) for the prevention of chemotherapy-induced alopecia

Abstract

Purpose

Chemotherapy-induced alopecia (CIA) negatively affects psychosocial health and quality of life (QoL). Currently, there are no approved pharmacologic agents to prevent CIA. Here, we evaluated the safety, tolerability, and potential signal of efficacy of topical calcitriol (BPM31543) on CIA prevention.

Materials and methods

This Phase 1 trial included 23 female patients with breast cancer, gynecologic cancer, or sarcomas receiving a taxane-based chemotherapy. Patients received a 3 + 3 dose-escalation regimen at 5, 10, 20, 40, 60, and 80 μg/mL, with 3–6 patients per group. Patients applied topical BPM31543 to the scalp twice a day for 2 weeks prior to chemotherapy and continued until chemotherapy treatment was completed. The maximum tolerated dose (MTD) during first 28 day application was determined. Adverse event (AE) monitoring, pharmacokinetics, blinded photographic assessments, and patient self-assessment were evaluated.

Results

Out of 23 patients treated with BPM31543, 8 patients experienced at least 1 treatment-related adverse event (AE). The majority of AEs were mild to moderate in severity. Only 1 patient experienced SAEs (vomiting, nausea, fever, and flank pain) considered treatment related. Alopecia < 50% from baseline was observed in 8 patients at Week 7, and, of which 2 patients had < 50% alopecia maintained at Week 15. There were no detectable effects of topical BPM31543 on serum levels of calcitriol.

Conclusions

BPM31543 applied topically twice daily to the scalp is safe and well tolerated in patients receiving taxane-based chemotherapy. No DLT was observed at up to 80 µg/mL, and MTD was not reached. Based on the data from this trial, BPM31543 represents a promising therapy and warrants further investigation in Phase 2/3 trials.

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Funding

MEL and SBG have received research funding for this study from Berg LLC (Clinical Trial ID: NCT01588522) and are supported in part by the NIH/NCI Cancer Center Support Grant P30 CA008748.

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Correspondence to Mario E. Lacouture or Shari B. Goldfarb.

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Conflict of interest

MEL and SBG declare no conflicts of interest. HD, ST, KT, EMG, EB, NT, SL, ND, NRN, RS, and EG are former/current employees of BERG and have stock/stock options. BB and JJJ are current members of BERG’s Scientific Advisory Board.

Ethical approval

All procedures performed involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Lacouture, M.E., Dion, H., Ravipaty, S. et al. A phase I safety study of topical calcitriol (BPM31543) for the prevention of chemotherapy-induced alopecia. Breast Cancer Res Treat (2020). https://doi.org/10.1007/s10549-020-06005-6

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Keywords

  • Chemotherapy-induced alopecia
  • Quality of life
  • Alopecia
  • Calcitriol