Safety, Feasibility and Efficacy of Vitamin D Supplementation in Women With Metastatic Breast Cancer (SAFE-D)
Condition: Adult Women; Metastatic Breast Cancer; Estrogen Receptor Positive
MeSH terms: Breast Neoplasms
Intervention: Cholecalciferol
Intervention description: Enrolled women will receive 50,000 IU weekly supplementation of cholecalciferol for 8 weeks.
Intervention MeSH terms: Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic Breast Cancer; MBC; Vitamin D Supplementation; Symptom Management

Summary:

      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.
    

Eligibility criteria:

        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