Safety, Feasibility and Efficacy of Vitamin D Supplementation in Women With Metastatic Breast Cancer (SAFE-D)

Background: Several clinical trials are underway to investigate if variable forms of vitamin D (D2 vs. D3) prescribed at different doses (10,000-50,000 IUs/week) can improve the side-effects associated with treatment for estrogen receptor positive (ER+) breast cancer, specifically aromatase inhibitors (AIs.) Presumably for generalizability and potential safety purposes, these trials predominantly exclude women with metastatic breast cancer (MBC); a rapidly expanding sector of the cancer survivor population who experience significant treatment-related side-effects. Evaluation of the safety of vitamin D3 supplementation is crucial since supplementation can lead to high calcium and importantly, in lab studies have shown that vitamin D3 affects a gene that increases estrogen production. To assure that vitamin D3 does not affect the clinical effects of anti-estrogen therapies, the effect of vitamin D3 supplements on estrogen production requires an evaluation that further explores and defines its potential role in symptom management for this population. Objectives: This pilot study will evaluate the feasibility of vitamin D3 supplementation in women with MBC, providing much needed data on the preliminary safety and efficacy of this treatment in this patient population. This study will determine: 1) if weekly supplementation of high dose vitamin D3 increases serum vitamin D levels without adverse effects related to such therapy (primary aim); 2) the effects of vitamin D3 supplementation on symptom management (secondary aim); and 3) if vitamin D3 supplementation is associated with improved inflammation (exploratory aim.) Methods: This is an 8 week "proof of concept" study to monitor laboratory parameters and to assess potential effects on short-term outcomes. Adult, female patients (\>=18 years) with ER+ MBC (Stage IV) of any race/ethnicity and a history of vitamin D \< 30 mg/dl will be recruited from within and around LUMC. Following current clinical practice guidelines, eligible participants will receive 50,000 IUs of vitamin D3 weekly for 8 weeks. Laboratory values, muscle function and inflammation will be examined pre- and post-supplementation, while symptoms will be assessed at baseline, 4 and 8 weeks post-supplementation. We will assess if increases in vitamin D are associated with clinically significant improvements in symptoms and QOL, and decreased inflammation.

Sex

Female

Minimum age

18 Years

Inclusion Criteria:

1. Metastatic breast cancer (Stage IV)
2. Histologically confirmed estrogen receptor positive disease
3. Female
4. Serum 25(OH) \<30 ng/ml
5. Age ≥ 18 years
6. Pre or post-menopausal
7. ECOG Performance status 0-2
8. Adequate organ function as defined as GFR\> 30 mls/min and serum calcium ≤ 10.4 mg/dl
9. Any race/ethnicity
10. English speaking
11. No changes to MBC treatments within 30 days of enrollment and/or deemed clinically stable by their treating physician
12. Willingness to sign a written informed consent and complete questionnaires
13. Cease ingestion of vitamin D supplementation not study related

Exclusion Criteria:

1. Women with Stage I-III breast cancer
2. Serum 25(OH)D levels ≥ 30 ng/ml
3. Untreated CNS involvement
4. History of kidney stones
5. History of renal failure
6. History of hyperparathyroidism
7. History of hypersensitivity to vitamin D
8. Non-English speaking
9. Currently pregnant or lactating, or anticipating pregnancy
10. Unwilling to cease ingestion of calcium supplements (\>1000 mg/d)
11. Unwilling or unable to complete informed consent or study questionnaires
12. Psychiatric or other clinical conditions that preclude study compliance
13. Other important medical or safety considerations at the discretion of the investigator and/or study physician, including non-compliance with the study therapy or other activities

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