Safety Study of Topical Compound 31543 (Calcitriol, USP) in Patients Receiving Chemotherapy for Breast Cancer

• Determine Maximum Tolerated Dose (MTD) of Topical Compound 31543 [ Time Frame: up to 52 weeks ] [ Designated as safety issue: Yes ]
  To determine the maximum tolerated dose (MTD) of topical Compound 31543 (Calcitriol, USP) in patients with metastatic breast cancer receiving chemotherapy with paclitaxel.
  
  

• record and observe adverse events in patient use of topical compound 31543 to determine overall Safety and tolerability [ Time Frame: up to 52 weeks ] [ Designated as safety issue: Yes ]
  

This will be a dose escalation study to determine the maximum tolerated dose (MTD) and the overall safety and tolerability of a topical compound 31543 (Calcitriol) in patients with metastatic breast cancer undergoing chemotherapy with paclitaxel. A standard 3+3 dose escalation design will be employed with 3-6 patients at each dose level. Eligible patients ≥18 years of age and scheduled to receive either paclitaxel 80 mg/m2 3 weeks on followed by 1 week off or weekly with treatment breaks as per physician's discretion, will start applying the topical solution twice a day at each cohort dose level two weeks prior to initiation of chemotherapy and then continue twice daily for 3 months or until termination of chemotherapy treatment. If topical calcitriol will be found to be effective in preventing and/or diminishing paclitaxel-induced alopecia as determined by the photographic assessments and patient self assessment, patients will be allowed to continue topical application for the duration of their chemotherapy treatment, assuming no Dose Limiting Toxicity (DLTs) related to the topical agent are observed. Toxicity to the topical compound 31543 (Calcitriol) will be assessed on a weekly basis during the first 28 days of topical treatment and subsequently every four weeks by a study clinician, either a physician or a nurse. For the purpose of pharmacokinetic studies (PKs), blood samples will be collected on Day 1 of topical treatment at the following time points: pre-dose, at 2 hours, 4 hours, and 8 hours after a single application on the morning of Day 1. The second application of drug product will be applied 9-12 hours after the initial application and after the 8 hour PK sample. Thereafter, topical application frequency will be twice daily, morning and night. Subsequently, a PK sample will be taken 24 hours after the last dose of each 28 day treatment and before the first application of Day 1 of the next 28 day treatment cycle. This schedule will continue for three consecutive 28 day topical treatment cycles. As a secondary objective, potential efficacy of the topical calcitriol will be evaluated by photographic assessment. Photographic assessment will be performed using D-SLR camera system to ensure standardization and uniformity among all enrolled patients. The following five views will be obtained at each photographic assessment: bilateral sides of head/scalp view, front of head/face view, back of head/scalp view, and top of head/scalp view. These assessments will be performed at the following time points: at baseline, after one month of chemotherapy treatment, 3months, 6 months and 12 months. In addition, all patients will be asked to maintain a self-assessment diary that will require weekly assessment of hair thickness, hair fullness, hair breakage, and hair cosmetic qualities (ease of styling, etc.) on an analog 10 point scale throughout treatment to ensure compliance with topical therapy and assess patient reported efficacy. The study is expected to take place over a period of approximately 12 months, including the screening period.