Effects of Vitamin D in Patients With Breast Cancer

Study Overview
=================
Brief Summary
-----------------
This protocol is a randomized, phase 2 window of opportunity trial assessing the biological effects of short term oral vitamin D administration on breast cancer clinical and translational markers in patients awaiting surgery at the Ottawa Hospital. It takes advantage of the current wait times (2-8 weeks) for breast cancer surgery as a window of opportunity to rapidly assess biological changes with vitamin D intake.

Official Title
-----------------
A Phase 2 Randomized, Double-blind, Window of Opportunity Trial Evaluating Clinical and Correlative Effects of Vitamin D in Patients With Breast Cancer. The ICARUS Trial

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: Vitamin D3
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed female primary breast cancer patients whose surgery is planned for the next 2-8 weeks without neoadjuvant therapy as assessed by multidisciplinary team Age ≥18 years Clinically palpable tumour(s) (greater than or equal to 2 cm) Normal serum and urine calcium and serum PTH values at baseline (as defined by Ottawa Hospital) Written informed consent for study Exclusion Criteria: Patients with recurrent or metastatic breast cancer History of neoadjuvant hormonal therapy, chemotherapy, or radiation therapy in the last 6 months for their breast cancer or any other cancer treatment ECOG performance Status > 2 Hypercalciuria on initial baseline urine, defined as Ca/Creatinine Ratio> 1.0 Current or previous history of urolithiasis or hyperparathyroidism Abnormal hepatic function according to Ottawa Hospital norms (Total Bilirubin >2x upper limit of normal, ALT/AST >3x upper limit of normal)and/or abnormal renal function (Creatinine > 150 µmol/L) History of granulomatous disease such as tuberculosis or sarcoidosis. Intake of Vitamin D (cholecalciferol) supplement ≥ 2000 IU/day within the last 2 months Inability to comply with a study protocol in the opinion of the investigator (such as abuse of alcohol, drugs or psychotic states).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D3<br>Vitamin D3 40,000 iu per day by mouth | Drug: Vitamin D3<br>* Participants will take 4 capsules of Vitamin D which equals 40,000 IU by mouth daily during the wait time between diagnosis and surgery.<br>* Other names: cholecalciferol;|
| Placebo Comparator: Placebo<br>Placebo taken daily by mouth | Other: Placebo<br>* Participants will take 4 capsules of placebo by mouth daily during the wait time between diagnosis and surgery.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre and post vitamin D administration Ki67 levels and Caspase 3 levels (as assessed according to the apoptosis assay) | Participants will have Ki67 and Caspase 3 levels performed on the tissue that was used to initially diagnose breast cancer. Those levels will then be compared to the tissue acquired at the time of surgery which will occur 2-8 weeks from diagnosis. | baseline and 2-8 weeks from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum levels of 25-0HD and in vivo breast (cancer and non cancer) tissue levels of 1,25(OH) | Participant will have Serum levels of 25-0HD and in vivo breast cancer tissue levels of 1,25(OH) taken at baseline and surgery | Baseline and 2-8 weeks from baseline at the time of surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Breast