Safety Study of Compound 31543 (Calcitriol, USP) in Patients Receiving Taxane-based Chemotherapy Regimens for Advanced or Recurrent Disease

This study is currently recruiting participants.
Verified August 2013 by Berg, LLC
Sponsor:
Information provided by (Responsible Party):
Berg, LLC
ClinicalTrials.gov Identifier:
NCT01588522
First received: April 20, 2012
Last updated: August 12, 2013
Last verified: August 2013
  Purpose

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 or recurrent cancer of the breast, cervical, endometrial, ovarian, fallopian tube, primary peritoneal carcinoma or soft tissue and bone sarcoma, who are undergoing chemotherapy with a taxane-based (paclitaxel/nanoparticle albumin-bound paclitaxel/docetaxel) regimen.


Condition Intervention Phase
Breast Cancer
Cervical Cancer
Endometrial Cancer
Ovarian Cancer
Primary Peritoneal Carcinoma
Bone Sarcoma
Drug: compound 31543 Calcitriol
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase I Dose-Escalation Study, to Evaluate the Safety, Tolerability and Pharmacokinetics of a Topical Compound 31543 (Calcitriol, USP) in Adult Cancer Patients Receiving Taxane-based Chemotherapy Regimens for the Treatment of Advanced or Recurrent Disease

Resource links provided by NLM:


Further study details as provided by Berg, LLC:

Primary Outcome Measures:
  • 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 or recurrent cancer of the breast, cervical, endometrial, ovarian, fallopian tube, primary peritoneal carcinoma or soft tissue and bone sarcoma, who are undergoing chemotherapy with a taxane-based regimen


Secondary Outcome Measures:
  • 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 ]
  • Observe and determine potential efficacy of topical calcitriol [ Time Frame: weeks 7, 15, 27, and 54 ] [ Designated as safety issue: No ]
    As a secondary objective, potential efficacy of the topical Calcitriol will be evaluated by photographic assessment. Photographic assessment will be performed using a Canon Power Shot G12 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. Additionally, close up photographs will be taken at the same time points. They will include the mid-pattern of the scalp from a superior view and a vertex view with hair parted in the center and combed away from the center part. Photographs will be standardized for lighting, camera angle, and position to the participant's head. These assessments will be performed at the following time points: at baseline, weeks 7, 15, 27, and 54.


Estimated Enrollment: 18
Study Start Date: July 2012
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: dose-escalation of compound 31543
compound 31543 Calcitriol, Topical application, 1.0 mL to be applied twice daily, morning and night with 10-14 hours between applications
Drug: compound 31543 Calcitriol
topical compound 31543 will be applied to the scalp twice daily 7 +/- 2 days prior to the dose of chemotherapy and continue the application twice daily for 3 months or until termination of chemotherapy treatment.
Other Name: Calcitriol

Detailed Description:

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 or recurrent cancer of the breast, cervical, endometrial, ovarian, fallopian tube, primary peritoneal carcinoma or soft tissue and bone sarcoma, who are undergoing chemotherapy with a taxane-based (paclitaxel/nanoparticle albumin-bound paclitaxel/docetaxel) regimen. 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 a taxane-based regimen with treatment breaks as per physician's discretion, will start applying the topical solution twice a day at each cohort dose level two weeks or 7 days +/- 2 days prior to initiation of chemotherapy and then continue twice daily for 3 months or until termination of chemotherapy treatment. if topical Calcitriol is found to be effective in preventing and/or diminishing taxane chemotherapy-induced alopecia as determined by the photographic assessments and patient self-assessments, patients will be allowed to continue topical application for the duration of their chemotherapy treatment, assuming no Dose Limiting Toxicities (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 (+/- 30 minutes), 4 hours (+/- 30 minutes), and 8 hours (+/- 1 hour post dose)after a single application on the morning of Day 1. The second application of drug product will be applied 10-14 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 12 hours (+/- 2 hours) after the last dose of each 28 day treatment, 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 (PKs will be drawn at weeks 1, 5, 9, 13. In addition, if patient are still on study, a PK will also be drawn at week 54). As a secondary objective, potential efficacy of the topical Calcitriol will be evaluated by photographic assessment. Photographic assessment will be performed using a Canon Power Shot G12 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. Additionally, close up photographs will be taken at the same time points. They will include the mid-pattern of the scalp from a superior view and a vertex view with hair parted in the center and combed away from the center part. Photographs will be standardized for lighting, camera angle, and position to the participant's head. These assessments will be performed at the following time points: at baseline, weeks 7, 15, 27, and 54. Photographs for patients in each cohort representing baseline, and treatment weeks 7 and 15 will be presented blind to the study PI after at least 3 patients have completed 15 weeks of treatment. Photographs will also be taken at week 27 and week 54 of the study but will be included in the final photographic assessment as secondary information. In addition, all patients will be asked to maintain an application log throughout treatment to ensure compliance. Additionally, patients will maintain a self-assessment diary that will require assessment of hair thickness, hair fullness, hair breakage, and hair cosmetic qualities (ease of styling, etc.) on an analog 10 point scale to assess patient-reported efficacy. the PI clinical assessment of baseline, weeks 7 & 15 photographs will be used, together with the patient diary information, for the primary assessment of alopecia. The study is expected to take place over a period of approximately 12 months, including the screening period.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 cancer of the breast, cervical, endometrial, ovarian, fallopian tube, primary peritoneal carcinoma or soft tissue and bone sarcoma, with pathology confirmed at Memorial Sloan-Kettering Cancer Center (MSKCC)
  • Scheduled to receive a taxane-based (paclitaxel/nanoparticle albumin-bound paclitaxel/docetaxel) regimen, as per physician's discretion
  • Have no evidence of alopecia or mild alopecia (NCI CTCAE grade 1 alopecia defined as "hair loss of <50% of normal for that individual that is not obvious from a distance but only on close inspection; a different hair style may be required to cover the hair loss but it does not require a wig or hair piece to camouflage". Female-pattern baldness or age-related hair loss are allowed if not greater than grade 1, per NCI-CTCAE v. 4.0
  • ECOG Performance Score of 0 or 1 within 14 days prior to registration
  • Has baseline neutrophil counts of > 1500 cells/mm3 within 72 hours prior to registration
  • Has serum calcium less than or equal to ULN (for patients with an albumin lower than 3.0, a corrected calcium serum calcium = serum calcium +[0.8][3.5-serum albumin]) within 72 hours prior to registration

Exclusion Criteria:

  • Patients receiving calcium-lowering therapy or drugs that may affect calcium levels (e.g., calcitonin, mithramycin, phosphate, denosumab) within 4 weeks of initiation of topical calcitriol. Patients who have been managed with bisphosphonates or calcium-lowering therapy for 3 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 may not be concurrently enrolled on another trial or concurrently treated with another investigational agent)
  • 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 investigator.
  • 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.
  • Patients taking Vitamin D supplements during the study, unless they have been taking Vitamin D supplements for 30 days or more prior to the start of the study and that the dose of the Vitamin D supplement remain the same throughout the study.
  • 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).with the exception of subjects on stable therapy for more than six months
  • Patients receiving thiazides or furosemide diuretics, with the exception of subjects who have stable doses and have been on therapy for over six months
  • Patients with hypercalcemia or kidney stones
  • Patients that indicate they have significant hair breakage or hair damage and associated hair loss from hair over-processing within the last 30 days due to peroxide applications, permanent hair coloring, bleaches, streaking, perms, relaxers and/or hair oxidative dyes.
  • Alopecia grade 2 or greater as per NCI-CTCAE v.4.0, or significant hair loss or hair breakage
  • Prior radiation to the cranium
  • Pregnancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01588522

Contacts
Contact: Brian Berman, MD 305-933-6716 bbmdphd@gmail.com

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10022
Contact: Mario E Lacouture, MD    212-610-0079    lacoutum@mskcc.org   
Principal Investigator: Mario E Lacouture, MD         
Sub-Investigator: Shari Goldfarb, MD         
Sponsors and Collaborators
Berg, LLC
Investigators
Principal Investigator: Mario E Lacouture, MD Memorial Sloan-Kettering Cancer Center
Principal Investigator: Shari Goldfarb, MD Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: Berg, LLC
ClinicalTrials.gov Identifier: NCT01588522     History of Changes
Other Study ID Numbers: CTL0211
Study First Received: April 20, 2012
Last Updated: August 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Berg, LLC:
alopecia

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Endometrial Neoplasms
Uterine Cervical Neoplasms
Osteosarcoma
Ovarian Neoplasms
Sarcoma
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Uterine Diseases
Genital Diseases, Female
Uterine Cervical Diseases
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Endocrine System Diseases
Gonadal Disorders
Calcitriol
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on April 17, 2014