Anti-proliferative Effects of Vitamin D and Melatonin in Breast Cancer

Study Overview
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Brief Summary
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Investigators plan to carry out a study to investigate two different pills, Vitamin D and melatonin, and whether they can reduce the spread of cancer cells in the tumors of women with breast cancer. These pills are inexpensive and have very few side effects. A large number of studies using cell cultures and animals have shown that both vitamin D and melatonin can help destroy breast cancer cells. However thoughtful and well-designed studies are necessary on humans to see if they can decrease the spread of breast cancer, and possibly even prevent breast cancer. The proposed study aims to understand the anti-cancer activity of vitamin D and melatonin. This knowledge will assist in creating efficient cancer prevention strategies for Canadians. This study will include women with breast cancer who are being planned for surgery, and will assess whether treatment with vitamin D (dose of 2000 IU per day) in a group of 36 women, or melatonin (dose of 20mg per day) in another group of 36 women, or both pills together in yet another group of 36 women, reduces the spread of cancer cells when compared to a fourth group of 36 women who are treated with sugar pills. To do this we will measure a substance in the blood called Ki67, which provides information about the spread of cancer. Investigators will compare the Ki67 levels in the 4 groups, and all women will receive identical appearing pills so they will not know which treatment they received.

Official Title
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Anti-proliferative Effects of Vitamin D and Melatonin in Breast Cancer

Conditions
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Early Stage Breast Cancer

Intervention / Treatment
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* Drug: Melatonin
* Drug: Vitamin D
* Drug: Placebo (melatonin)
* Drug: Placebo (vitamin D)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Woman with histologically confirmed invasive breast cancer (ductal, lobular, or mixed) Planned to undergo definitive surgery, either lumpectomy or mastectomy in 3 or more weeks Exclusion Criteria: Less than 18 years of age Stage IIIB or IV disease Inoperable locally advanced or metastatic breast cancer Neoadjuvant chemotherapy is intended Currently taking vitamin D supplements Currently taking melatonin supplements Previously taking vitamin D or melatonin supplements within the last 3 months Currently taking a multivitamin and not willing to discontinue for the duration of the study Hyperparathyroid disease or other calcium disturbance in the past five years Active renal stones in the last six months Renal failure (creatinine > 190 mmol/L) Hypercalcemia (serum calcium > 2.6 mmol/L) Known pregnancy Participation in another clinical trial where the patient receives any other investigational product Unwilling or unable to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Melatonin and Vitamin D<br> | Drug: Melatonin<br>* Melatonin 20mg taken orally once daily. This is in the form of one capsule which contains two pills of melatonin, 10 mg each.<br>Drug: Vitamin D<br>* Vitamin D 2000 IU taken orally once daily. This is in the form of one capsule which contains two pills of vitamin D, 1000 IU each.<br>|
| Experimental: Placebo and Vitamin D<br> | Drug: Vitamin D<br>* Vitamin D 2000 IU taken orally once daily. This is in the form of one capsule which contains two pills of vitamin D, 1000 IU each.<br>Drug: Placebo (melatonin)<br>* Overencapsulated placebo capsule which contains an inert substance. The capsule appears identical to the capsule which contains melatonin tablets.<br>|
| Experimental: Melatonin and Placebo<br> | Drug: Melatonin<br>* Melatonin 20mg taken orally once daily. This is in the form of one capsule which contains two pills of melatonin, 10 mg each.<br>Drug: Placebo (vitamin D)<br>* Overencapsulated placebo capsule which contains an inert substance. The capsule appears identical to the capsule which contains vitamin D tablets.<br>|
| Placebo Comparator: Placebo and Placebo<br> | Drug: Placebo (melatonin)<br>* Overencapsulated placebo capsule which contains an inert substance. The capsule appears identical to the capsule which contains melatonin tablets.<br>Drug: Placebo (vitamin D)<br>* Overencapsulated placebo capsule which contains an inert substance. The capsule appears identical to the capsule which contains vitamin D tablets.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ki67 | The primary outcome is the difference in proliferation rate of Ki67 in the tumour (expressed as the percentage of tumour cells expressing Ki67). Ki67 will be measured on the original core biopsy (pre-treatment) and on the lumpectomy/mastectomy specimen (post-treatment). | From time of initial biopsy to the final surgery, which is on average 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| microRNA | Change in serum profile of microRNA at the time of surgery (lumpectomy or mastectomy, post-treatment) will be compared to the time of initial biopsy (pre-treatment). | At the time of surgery compared to time of biopsy, which is on average 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, melatonin, vitamin d, ki67