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

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.

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: calcium and cholecalciferol; Drug: calcium and cholecalciferol

• Study Type: Interventional
• Enrollment (Actual): 215
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34298
    • CRLC Val d'Aurelle-Paul Lamarque

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Conventional vitamin D and calcium supplementation; Conventional vitamin D and calcium supplementation with 2 daily OROCAL VITAMINE D3® (500 mg calcium/200 IU cholecalciferol) tablets.	Drug: calcium and cholecalciferol; Tablet to suck: calcium 500 mg bid, cholecalciferol 200 IU bid; Drug: calcium and cholecalciferol; 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
EXPERIMENTAL: vitamin D supplementation tailored to vitamin D deficiency; 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; Tablet to suck: calcium 500 mg bid, cholecalciferol 200 IU bid; Drug: calcium and cholecalciferol; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle

Publications and helpful links

General Publications

• Jacot W, Firmin N, Roca L, Topart D, Gallet S, Durigova A, Mirr S, Abach L, Pouderoux S, D'Hondt V, Bleuse JP, Lamy PJ, Romieu G. Impact of a tailored oral vitamin D supplementation regimen on serum 25-hydroxyvitamin D levels in early breast cancer patients: a randomized phase III study. Ann Oncol. 2016 Jul;27(7):1235-41. doi: 10.1093/annonc/mdw145. Epub 2016 Mar 30.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (ACTUAL): December 1, 2014
• Study Completion (ACTUAL): December 1, 2014

Study Registration Dates

• First Submitted: November 24, 2011
• First Submitted That Met QC Criteria: November 28, 2011
• First Posted (ESTIMATE): November 29, 2011

Study Record Updates

• Last Update Posted (ACTUAL): September 10, 2019
• Last Update Submitted That Met QC Criteria: September 6, 2019
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Breast cancer; Vitamin D supplementation; in neoadjuvant; adjuvant setting
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Breast Neoplasms; Vitamin D Deficiency; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Calcium; Calcium, Dietary
• Other Study ID Numbers: VITACAL; VA 2010/12 (OTHER: VA 2010/12); 2010-023459-27 (EUDRACT_NUMBER)