Abstract 5748
Background
Chemotherapy-induced alopecia (CIA) negatively effects psychosocial health and quality of life. Currently there are no FDA approved pharmacologic agents available to prevent CIA. Topical calcitriol, a vitamin D3 analog, has been shown in murine studies to reduce CIA, likely due to arrest of cell cycle in healthy hair follicles, and reduction in the sensitivity of follicular epithelium to chemotherapy.
Methods
A 3 + 3 dose-escalation Phase 1 study with 3-6 patients at 5, 10, 20, 40, 60, 80 μg/mL was examined in 23 patients (pts) with breast cancer, gynecologic cancer or sarcomas receiving a taxane-based chemotherapy regimen. Pts applied 1mL of topical calcitriol (BPM31543) to the scalp BID, ≥ 5 days prior to chemotherapy for 3 months or treatment completed. The maximum tolerated dose (MTD) was determined by dose escalation in stepwise increments of the prior dose, in the absence of dose-limiting toxicity (DLT) during the first 28 days of application. Adverse event (AE) monitoring, pharmacokinetics, blinded photographic assessments and patient self-assessment were assessed.
Results
22 treated pts experienced 1 treatment emergent adverse event (TEAE). The most frequently experienced TEAEs were fatigue (47.8%), nausea (39.1%), peripheral sensory neuropathy (30.4%), maculopapular rash and elevated vitamin D (26.1%). Elevated vitamin D and rash were possibly or probably related to treatment, while fatigue, nausea, neuropathy were likely due to chemotherapy. The majority of AEs were mild to moderate in severity. 13 TEAEs were considered Grade 3, but were not considered treatment related by the investigators. Hair loss <50% from baseline was observed in 8 pts at Week 7. At Week 15, 2 pts had <50% hair loss maintained. There were no detectable effects of topical BPM31543 on serum levels of calcitriol.
Conclusions
BPM31543 applied topically twice daily to the scalp in patients receiving taxane-based chemotherapy is safe and well-tolerated with no apparent differences in safety between doses. Here, no DLT was observed at up to 80 µg/mL and MTD was not reached. Some efficacy was detected at each dose. These data are encouraging and support further investigation in Phase 2/3 trials.
Clinical trial identification
NCT01588522.
Legal entity responsible for the study
BERG, LLC.
Funding
BERG, LLC.
Editorial Acknowledgement
Khampaseuth Thapa, BERG, LLC.
Disclosure
M. Lacouture: Research sponsorship: BERG, LLC, Veloce Pharma. H. Dion, S. Ravipaty, V.R. Akmaev: Employee and stock options: BERG, LLC. R. Sarangarajan: Co-founder, employee and stock options: BERG, LLC. J.J. Jimenez, S. Goldfarb: Research sponsorship: BERG, LLC. N.R. Narain: Co-founder, President, CEO, stock options: BERG, LLC. B. Berman: Research sponsorship; BERG, LLC., Leo, Biofrontera, Tigercat; Stock or other ownership: Dermira, Sonoma, Celumigen.
Resources from the same session
2595 - Real-Life Utilization of Genomic testing for invasive Breast Cancer patients in Italy and France reduces Chemotherapy Recommendations
Presenter: Sandro Barni
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
2343 - Benefit of adjuvant chemotherapy in hormone receptor-positive, HER2-negative, invasive lobular carcinoma of the breast
Presenter: Alexandre De Nonneville
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
2990 - Baseline lymphocyte counts predict distant recurrence in early breast cancer
Presenter: Gun Min Kim
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
4532 - A propensity score analysis exploring the impact of the addition of adjuvant chemotherapy (aCT) to hormone therapy (aHT) in a multi-center series of resected luminal early stage pure Invasive Lobular Breast Carcinoma (ILC).
Presenter: Luisa Carbognin
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
2344 - Benefit of Adjuvant Systemic Therapies in HR+ HER2- pT1ab Node-Negative Breast Carcinomas
Presenter: Alexandre De Nonneville
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
3525 - Anti-proliferative effect of oral metronomic vinorelbine in PAM50 Luminal/HER2-negative early breast cancer (SOLTI-1501 VENTANA): an open-label, randomized, three-arm, multicenter, window-of-opportunity study
Presenter: Aleix Prat
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
3908 - Clinicopathologic significance of androgen receptor expression and discordant receptor status during progression in breast cancer
Presenter: Chan Heun Park
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
4075 - The outcomes of early breast cancers utilizing the Oncotype Dx Recurrence score (RS) instead of Clinico-pathological (CP) factors for prognostic risk assessment: A Single Institution Experience
Presenter: Adhar Alsayed
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
738 - Circulating tumor cells as a prognostic marker in non metastatic breast cancer patients.
Presenter: Summar Elmorshidy
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
3151 - Molecular subtyping of breast cancer by dedicated breast PET
Presenter: Satoshi Sueoka
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract