Study of Vitamin D Supplementation Tailored to Vitamin D Deficiency in Breast Cancer Patients

Study Overview
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Brief Summary
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The purpose of this study is to compare normalization of vitamin D serum level after 6 months of vitamin D supplementation adjusted to baseline vitamin D serum level vs.conventional vitamin D supplementation.

Official Title
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Randomized Phase III Trial Comparing Conventional Vitamin D Supplementation vs. Vitamin D Supplementation Tailored to Vitamin D Deficiency in Breast Cancer Patients Treated by Neoadjuvant or Adjuvant Chemotherapy.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: calcium and cholecalciferol
* Drug: calcium and cholecalciferol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Breast adenocarcinoma treated by neoadjuvant or adjuvant chemotherapy within 12 months prior to study enrollment WHO performance status 0-1 Age ≥18 years old Affiliation to a social security regime or beneficiary of equivalent social protection Written informed consent provided before any study specific procedures Complementary inclusion criterion for randomization - Proved vitamin D deficiency as defined by serum vitamin D level lower than 30 ng/ml (75 nmol/L). Exclusion Criteria: Metastatic disease History or presence of any other malignancy (except curatively treated nonmelanoma skin cancer or in situ cervix carcinoma) …………. traités dans les 5 ans précédents. Contraindication to calcium or cholecalciferol Known severe hypersensitivity to vitamin D or to calcium supplementation or to one of the excipients. Disease and/or medical conditions accompanied by hypercalcaemia and/or hypercalciuria Calcium lithiasis and tissue calcification Hypervitaminosis D Presence of significant comorbidities: i) Uncontrolled endocrine disease ii) Known disorders of calcium phophorus laboratory testing iii) Proved osteopenia or osteoporosis requiring vitamin D and calcium supplements Concomitant treatment with other experimental products or another vitamin D calcium treatment Pregnancy, breastfeeding or of reproductive potential not using an effective contraceptive method Legal inability or restricted legal ability. Medical or psychological conditions not allowing proper study completion or informed consent signature

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional vitamin D and calcium supplementation<br>Conventional vitamin D and calcium supplementation with 2 daily OROCAL VITAMINE D3® (500 mg calcium/200 IU cholecalciferol) tablets. | Drug: calcium and cholecalciferol<br>* Tablet to suck: calcium 500 mg bid, cholecalciferol 200 IU bid<br>|
| Experimental: vitamin D supplementation tailored to vitamin D deficiency<br>Conventional calcium supplementation with 2 daily OROCAL 500® (500 mg calcium) tablets to suck + vitamin D3 supplementation (UVÉDOSE®, cholecalciferol, 100 000 IU drinkable solution, 2 ml vial) whose schedule of administration depends on vitamin deficiency level: 100 000 IU of vitamin D3 at D1, D15, D28 and D43 if 25OHD level < 10 ng/mL 100 000 IU of vitamin D3 at D1, D15, D28 if 10 ng/mL ≤ 25OHD level < 20 ng/mL 100 000 IU of vitamin D3 at D1 if 20 ng/mL ≤ 25OHD level < 30 ng/mL | Drug: calcium and cholecalciferol<br>* Tablet: calcium 500 mg bid + 2 ml drinkable solution cholecalciferol 100 000 IU whose schedule of administration depends on vitamin deficiency level: 100 000 IU of vitamin D3 at D1, D15, D28 and D43 if 25-OHD level < 10 ng/mL 100 000 IU of vitamin D3 at D1, D15, D28 if 10 ng/mL ≤ 25-OHD level < 20 ng/mL 100 000 IU of vitamin D3 at D1 if 20 ng/mL ≤ 25-OHD level < 30 ng/mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the increase in normalization of serum vitamin D level | To compare the increase in normalization of serum vitamin D level adjusted to baseline level in patients receiving either vitamin D supplementation tailored to vitamin D deficiency or conventional vitamin D supplementation. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline vitamin D/calcium status in this patient population |  | Baseline | 
| Normalization rate of serum 25-OHD level |  | 12, 18 and 24 months | 
| Normalization rate of serum 25-OHD level in control patients who shift to experimental strategy |  | 6 months after crossover | 
| Clinical and biological tolerance profile | According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.0 | During treament administration (can last up to 24 months) | 
| Treatment compliance | Treatment compliance will be assessed using a patient record book | During treatment administration (can last up to 24 months) | 
| Quality of life | Quality of life is assessed using the EORTC QLQ-C30 questionnaire | 24 months | 
| Impact of study treatments on bone and joint pains induced by aromatase inhibitors |  | During treatment administration (can last up to 24 months) | 
| Changes in vitamin and calcium biological markers |  | Up to 24 months | 
| Predictive value of individual biomarkers |  | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Vitamin D supplementation, in neoadjuvant, adjuvant setting