Back to resultsEffect of High Dose Vitamin D on Cancer Biomarkers and Breast Cancer Tumors
Primary Purpose
Breast Cancer, Invasive Breast Carcinoma, Ductal Carcinoma In-situ
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Vitamin D3
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring DCIS, IBC, Breast Cancer, Invasive Breast Carcinoma, High Grade Ductal Carcinoma in-situ
Eligibility Criteria
Inclusion Criteria:
- Patients must have histologically confirmed invasive breast carcinoma (IBC) or high grade (DIN3) Ductal Carcinoma in-situ (DCIS) and be scheduled for primary surgery.
- Patients must be recommended/scheduled for primary surgery.
- Female patients 18 years of age or older.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
Patients must have normal organ function as defined below:
- Aspartate aminotransferase (AST/SGOT) < 4 times institutional upper limit of normal.
- Alanine transaminase (ALT/SGPT) < 4 times institutional upper limit of normal.
- Serum Bilirubin < 1.5 mg/dl.
- Serum Alkaline Phosphatase < 4 times institutional upper limit.
- Creatinine within normal institutional limits OR; Creatinine clearance >/= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.
- Albumin within normal institutional limits
- Women of childbearing potential (WoCBP) must have a negative (serum or urine) pregnancy test and agree to use barrier contraception while on treatment and for 30-days thereafter.
- Ability to understand and the willingness to sign a written informed consent document by patient or their legal representatives.
Exclusion Criteria:
- Previous history of breast cancer diagnosis or treatment.
- Synchronous bilateral breast cancer.
- Metastatic breast cancer
- Patients recommended for neoadjuvant systemic therapy.
- Patients may not be receiving any other investigational agents or have participated in any investigational drug study within 4 weeks preceding the start of study treatment.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements.
- Concurrent other malignancy
- Uncontrolled hypertension
- Chronic cholestatic or alcoholic liver disease
- Chronic pancreatitis
- Kidney impairment or renal stones
- History of parathyroidectomy
- Hypercalcemia, defined as serum level >11 mg/dl.
- Abnormal laboratory data for: AST (SGOT), ALT (SGPT), Serum Bilirubin, Alkaline phosphatase, Creatinine and/or Creatinine clearance, and Albumin.
- Patients receiving medications that are incompatible with VD.
- Prior or known allergic reaction(s) to Vitamin D or other forms of Vitamin D.
- Female patients who are pregnant or breast feeding.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Active Comparator
Active Comparator
Experimental
Arm Label
Phase 1 - Group A - VD 3 Weeks
Phase 1 - Group B - VD 4 Weeks
Phase 1 - Group C - VD 5 Weeks
Phase 2 - VD
Arm Description
Weekly oral dose of 50,000 IU Vitamin D3 (VD) for 3 weeks.
Weekly oral dose of 50,000 IU Vitamin D3 (VD) for 4 weeks
Weekly oral dose of 50,000 IU Vitamin D3 (VD) for 5 weeks.
Weekly oral dose of 50,000 IU Vitamin D3 (VD) therapy for the duration selected from the phase I part of the study.
Outcomes
Primary Outcome Measures
Phase 1 - Rate of Treatment-Related Toxicity in Subjects
Rate of treatment-related adverse events and other toxicities in subjects.
Phase 2 - Rate of Favorable Treatment Response in Subjects Receiving Protocol Therapy Given Within the Optimal Duration Determined in Phase 1.
Rate of subjects achieving a "favorable treatment response" to protocol therapy given within the optimal duration determined in Phase 1. The effect of VD therapy will be assessed in terms of change in expression of VDR, ER, PR, HER2/neu, AR, Ki-67, E-cadherin and EGFR comparing surgical specimen (post-VD treatment) and baseline biopsy specimen (pre-VD treatment). The effect of VD will be described as increased expression, decreased expression or no change in expression of each marker/receptor measured.
The expression of nuclear receptors/proteins (VDR, Ki-67, ER, PR, AR,) will be scored based on the percentage of positively staining nuclei as follows:
0 (Negative) if <1%
+1 (Weak) if >1-10%
+2 (Moderate) if >10-50%
+3 (Strong) if >50%
A decrease in the expression of Ki-67 by ≥+1 after treatment is considered a "favorable treatment response".
Secondary Outcome Measures
Phase 1 - Optimal Duration of Once-Weekly Protocol Therapy
The determination of the optimal duration of once-weekly protocol therapy, 3, 4 or 5 weeks, as preoperative treatment to achieve a "favorable" treatment response in subjects with the study disease. The effect of VD therapy will be assessed in terms of change in expression of VDR, ER, PR, HER2/neu, AR, Ki-67, E-cadherin and EGFR comparing surgical specimen (post-VD treatment) and baseline biopsy specimen (pre-VD treatment). The effect of VD will be described as increased expression, decreased expression or no change in expression of each marker/receptor measured.
The expression of nuclear receptors/proteins (VDR, Ki-67, ER, PR, AR,) will be scored based on the percentage of positively staining nuclei as follows:
0 (Negative) if <1%
+1 (Weak) if >1-10%
+2 (Moderate) if >10-50%
+3 (Strong) if >50%
A decrease in the expression of Ki-67 by ≥+1 after treatment is considered a "favorable treatment response".
Phase 2 - Rate of Treatment-Related Toxicity in Subjects
Rate of treatment-related adverse events and other toxicities in subjects.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02856503
Brief Title
Effect of High Dose Vitamin D on Cancer Biomarkers and Breast Cancer Tumors
Official Title
Phase I/II Study Evaluating Safety and Effects of Preoperative High-Dose Vitamin D on the Receptors, Biomarkers and Pathological Characteristics of High Grade DCIS or Invasive Breast Cancer.
Study Type
Interventional
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Withdrawn
Why Stopped
Lack of Funding
Study Start Date
January 2019 (Anticipated)
Primary Completion Date
January 2023 (Anticipated)
Study Completion Date
January 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Eli Avisar
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
High-doses of Vitamin D (VD) may be used as targeted therapy against breast cancer. The investigators will assess the effect of high dose VD on the following biomarkers in the breast cancer cells: VDR, estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor 2 (Her2/neu), androgen receptor (AR), as well as epidermal growth factor receptor 1 (EGFR) and Ki-67, as markers of proliferation, and E-cadherin, a marker of invasion and metastasis.
Detailed Description
This is a phase I/II open-label, non-randomized study. In phase I, a fixed weekly course of oral high-dose Vitamin D (VD) is planned for either 3, 4 or 5 weeks; patients will be sequentially enrolled into 3 groups (A, B or C respectively) in a manner such that no more than two patients may have treatment-limiting toxicities (TLTs).
After the group with the optimal duration of VD therapy to achieve a "favorable response" is determined, phase II will begin enrollment.
Patients must be scheduled to have surgery performed within 2- weeks of the last dose of VD.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Invasive Breast Carcinoma, Ductal Carcinoma In-situ
Keywords
DCIS, IBC, Breast Cancer, Invasive Breast Carcinoma, High Grade Ductal Carcinoma in-situ
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase 1 - Group A - VD 3 Weeks
Arm Type
Experimental
Arm Description
Weekly oral dose of 50,000 IU Vitamin D3 (VD) for 3 weeks.
Arm Title
Phase 1 - Group B - VD 4 Weeks
Arm Type
Active Comparator
Arm Description
Weekly oral dose of 50,000 IU Vitamin D3 (VD) for 4 weeks
Arm Title
Phase 1 - Group C - VD 5 Weeks
Arm Type
Active Comparator
Arm Description
Weekly oral dose of 50,000 IU Vitamin D3 (VD) for 5 weeks.
Arm Title
Phase 2 - VD
Arm Type
Experimental
Arm Description
Weekly oral dose of 50,000 IU Vitamin D3 (VD) therapy for the duration selected from the phase I part of the study.
Intervention Type
Drug
Intervention Name(s)
Vitamin D3
Other Intervention Name(s)
Toxiferol, Cholecalciferol
Intervention Description
Weekly oral dose of Vitamin D3 per protocol.
Primary Outcome Measure Information:
Title
Phase 1 - Rate of Treatment-Related Toxicity in Subjects
Description
Rate of treatment-related adverse events and other toxicities in subjects.
Time Frame
From Baseline to 30 days (+ 5 days) After Last Dose of Protocol Therapy, About 3 Months
Title
Phase 2 - Rate of Favorable Treatment Response in Subjects Receiving Protocol Therapy Given Within the Optimal Duration Determined in Phase 1.
Description
Rate of subjects achieving a "favorable treatment response" to protocol therapy given within the optimal duration determined in Phase 1. The effect of VD therapy will be assessed in terms of change in expression of VDR, ER, PR, HER2/neu, AR, Ki-67, E-cadherin and EGFR comparing surgical specimen (post-VD treatment) and baseline biopsy specimen (pre-VD treatment). The effect of VD will be described as increased expression, decreased expression or no change in expression of each marker/receptor measured.
The expression of nuclear receptors/proteins (VDR, Ki-67, ER, PR, AR,) will be scored based on the percentage of positively staining nuclei as follows:
0 (Negative) if <1%
+1 (Weak) if >1-10%
+2 (Moderate) if >10-50%
+3 (Strong) if >50%
A decrease in the expression of Ki-67 by ≥+1 after treatment is considered a "favorable treatment response".
Time Frame
Up to 7 Weeks
Secondary Outcome Measure Information:
Title
Phase 1 - Optimal Duration of Once-Weekly Protocol Therapy
Description
The determination of the optimal duration of once-weekly protocol therapy, 3, 4 or 5 weeks, as preoperative treatment to achieve a "favorable" treatment response in subjects with the study disease. The effect of VD therapy will be assessed in terms of change in expression of VDR, ER, PR, HER2/neu, AR, Ki-67, E-cadherin and EGFR comparing surgical specimen (post-VD treatment) and baseline biopsy specimen (pre-VD treatment). The effect of VD will be described as increased expression, decreased expression or no change in expression of each marker/receptor measured.
The expression of nuclear receptors/proteins (VDR, Ki-67, ER, PR, AR,) will be scored based on the percentage of positively staining nuclei as follows:
0 (Negative) if <1%
+1 (Weak) if >1-10%
+2 (Moderate) if >10-50%
+3 (Strong) if >50%
A decrease in the expression of Ki-67 by ≥+1 after treatment is considered a "favorable treatment response".
Time Frame
Up to 7 Weeks
Title
Phase 2 - Rate of Treatment-Related Toxicity in Subjects
Description
Rate of treatment-related adverse events and other toxicities in subjects.
Time Frame
From Baseline to 30 days (+ 5 days) After Last Dose of Protocol Therapy, About 3 Months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must have histologically confirmed invasive breast carcinoma (IBC) or high grade (DIN3) Ductal Carcinoma in-situ (DCIS) and be scheduled for primary surgery.
Patients must be recommended/scheduled for primary surgery.
Female patients 18 years of age or older.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
Patients must have normal organ function as defined below:
Aspartate aminotransferase (AST/SGOT) < 4 times institutional upper limit of normal.
Alanine transaminase (ALT/SGPT) < 4 times institutional upper limit of normal.
Serum Bilirubin < 1.5 mg/dl.
Serum Alkaline Phosphatase < 4 times institutional upper limit.
Creatinine within normal institutional limits OR; Creatinine clearance >/= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.
Albumin within normal institutional limits
Women of childbearing potential (WoCBP) must have a negative (serum or urine) pregnancy test and agree to use barrier contraception while on treatment and for 30-days thereafter.
Ability to understand and the willingness to sign a written informed consent document by patient or their legal representatives.
Exclusion Criteria:
Previous history of breast cancer diagnosis or treatment.
Synchronous bilateral breast cancer.
Metastatic breast cancer
Patients recommended for neoadjuvant systemic therapy.
Patients may not be receiving any other investigational agents or have participated in any investigational drug study within 4 weeks preceding the start of study treatment.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements.
Concurrent other malignancy
Uncontrolled hypertension
Chronic cholestatic or alcoholic liver disease
Chronic pancreatitis
Kidney impairment or renal stones
History of parathyroidectomy
Hypercalcemia, defined as serum level >11 mg/dl.
Abnormal laboratory data for: AST (SGOT), ALT (SGPT), Serum Bilirubin, Alkaline phosphatase, Creatinine and/or Creatinine clearance, and Albumin.
Patients receiving medications that are incompatible with VD.
Prior or known allergic reaction(s) to Vitamin D or other forms of Vitamin D.
Female patients who are pregnant or breast feeding.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eli Avisar, MD
Organizational Affiliation
University of Miami
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Effect of High Dose Vitamin D on Cancer Biomarkers and Breast Cancer Tumors
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