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A Phase I Dose-escalation Study, to Evaluate the Safety, Tolerability and Pharmacokinetics of a Topical Compound 31543 (Calcitriol, USP) in Adult Patients Receiving Chemotherapy for the Treatment of Breast Cancer

Phase 1
18 Years
Open (Enrolling)
Alopecia, Breast Cancer

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Trial Information

A Phase I Dose-escalation Study, to Evaluate the Safety, Tolerability and Pharmacokinetics of a Topical Compound 31543 (Calcitriol, USP) in Adult Patients Receiving Chemotherapy for the Treatment of Breast Cancer

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.

Inclusion Criteria:

- adult female patients at least 18 years of age

- able to fully understand and participate in the informed consent process

- history of locally advanced unresectable and/or metastatic breast cancer with
pathology confirmed at Memorial Sloan-Kettering Cancer Center (MSKCC)

- 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

- Have no evidence of alopecia with a full set of hair

Exclusion Criteria:

- Patients receiving calcium-lowering therapy or drugs that may affect calcium levels
(e.g., calcitonin, mithramycin, phosphate) within 4 weeks of initiation of topical
calcitriol. Patients who have been managed with bisphosphonates for 6 months or
greater prior to the start of the trial and have demonstrated evidence for stability
of calcium metabolism would be considered eligible for participation in the trial.

- Has a history of drug or alcohol abuse within 1 year of study enrollment as
determined by the investigator.

- Patients who elect to shave the scalp hair prior to the initiation of chemotherapy or
who plan to do so during the chemotherapy treatment.

- Any dermatological condition that in the opinion of the investigator will affect the
absorption of the study medication, e.g. Atopic Dermatitis, etc.

- Has participated in any investigational trial within 30 days or six half-lives of its
biologic activity whichever is longer, before the start of study.

- Patients with a history of hypercalcemia or vitamin D toxicity, or hospitalization
for treatment of angina, myocardial infarction, or congestive heart failure or
psychiatric illness currently or within 30 days of study entry as determined by the

- Has a history of significant allergies (including asthma, food or drug allergies) as
determined by the investigator.

- Has any condition that interferes with the ability of the subject to understand or
comply with the requirements of the study.

- Has serum calcium more than ULN (for patients with an albumin lower than 3.0, a
corrected calcium serum calcium = serum calcium +[0.8][3.5- serum albumin]).

- Has been on >400 IU Vitamin D supplements within one week prior to the start of the

- Patients treated with medications that are known to affect calcium levels within 4
weeks of initiation of topical therapy (>500 IU vitamin A, calcium supplements,
fluoride, antiepileptics).

- Patients receiving thiazides or furosemide diuretics

- Patients with hypercalcemia or kidney stones

- Patients that indicate they have significant hair breakage or hair damage and
associated hair loss from hair overprocessing within the last 30 days due to peroxide
applications, permanent hair coloring, bleaches, streaking, perms, relaxers and/or
hair oxidative dyes.

- Any visible signs of androgenic alopecia or alopecia areata or significant hair loss,
hair thinning, or hair breakage.

- Prior radiation to the cranium

- Pregnancy

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Outcome Measure:

Determine Maximum Tolerated Dose (MTD) of Topical Compound 31543

Outcome Description:

To determine the maximum tolerated dose (MTD) of topical Compound 31543 (Calcitriol, USP) in patients with metastatic breast cancer receiving chemotherapy with paclitaxel.

Outcome Time Frame:

up to 52 weeks

Safety Issue:


Principal Investigator

Mario E Lacouture, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

July 2012

Completion Date:

August 2013

Related Keywords:

  • Alopecia
  • Breast Cancer
  • Alopecia
  • Alopecia Areata
  • Breast Neoplasms



Memorial Sloan-Kettering Cancer Center New York, New York  10021