This was a multi-center, single arm, dose-escalation Phase 1 study to determine the maximum tolerated dose (MTD), PK, and the overall safety and tolerability of Compound 31543 in patients with a diagnosis of early-stage or locally advanced, unresectable and/or metastatic cancer, or patients with operable cancer, who were scheduled to receive follow up treatment with a taxane-based chemotherapy regimen, as per the physician's discretion. A standard 3+3 dose escalation design was employed, over 6 dose levels, with 3 to 6 patients at each dose level. Eligible patients in each cohort, \>18 years of age and scheduled to receive a taxane-based regimen with treatment breaks as per physician's discretion, initially received or applied the topical formulation of Compound 31543 to the scalp twice daily either for 2 weeks or 7 ± 2 days (if the patient was unable or unwilling to undergo 2 weeks of pre-treatment) prior to the first dose of chemotherapy and continued the application twice daily for the duration of the individual patient's chemotherapy (up to a maximum of 54 weeks).To determine the MTD for Compound 31543, dose escalation was conducted in stepwise increments, in the absence of dose-limiting toxicity (DLT) defined as clinically significant Grade 3 or 4 non-hematologic toxicity assessed as possibly, probably, or definitely related to Compound 31543 and not to the taxane-based chemotherapy, as best determined by investigator; assessment of DLTs was made weekly during the first 28 days of Compound 31543 treatment and subsequently thereafter every 4 weeks.
Pharmacokinetic (PK) data were evaluated for each dose level before escalation of Compound 31543 to the next dose level in all patients. PK blood samples were collected on Day 1 prior (pre-dose) to the first-morning dose of topical Compound 31543 and at 2, 4, and 8 hours post-dose after the first application of Compound 31543 on Day 1. PK samples were also collected 12 hours after the last, evening dose of Compound 31543 (i.e., before the first Day 1 of the next 28-day treatment) on Weeks 5, 9, 13, and 54.
Potential efficacy of the Compound 31543 was evaluated by photographic assessments and self-assessment diaries performed at baseline and Weeks 7, 15, 27, and 54. Photographic assessments were performed using a Canon digital camera system on views of the front of head/face, bilateral sides of head, and back and top of head/scalp view, as well as close-up photographs of a superior view and a vertex view with hair parted in the center and combed away from the part. Photographs were standardized for lighting, camera angle, and position to the participant's head.
Additionally, patients maintained a medication application diary and a self-assessment diary. The patient completed diary collected patient-reported assessments of hair thickness, fullness, volume, breakage, and cosmetic qualities (ease of styling, etc.) based on a 10-point analog scale for each parameter/question during the first 15 weeks after initiating calcitriol Compound 31543 and at Weeks 19, 23, and 27.
