Clinical trial NCT02186015: Safety, Feasibility and Efficacy of Vitamin D Supplementation in Women With Metastatic Breast Cancer (SAFE-D)
Official title: Safety, Feasibility and Efficacy of Vitamin D Supplementation in Women With Metastatic Breast Cancer (SAFE-D)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Women
Metastatic Breast Cancer
Estrogen Receptor Positive
Keywords: Metastatic Breast Cancer
MBC
Vitamin D Supplementation
Symptom Management
Lead sponsor: Loyola University
Sponsor class: OTHER
First posted: 2014-07-10
Enrollment: 43
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: Study Aims

Several clinical trials are underway to investigate if vitamin D2 or D3 provided at various doses (10,000-50,000 IUs/week) can improve the side-effects associated with anti-estrogen therapies, specifically aromatase inhibitors (AIs). However, these current trials use variable forms of vitamin D and predominantly include women with Stage I-III disease, excluding women with metastatic breast cancer. Evaluation of the safety of vitamin D3 supplementation is crucial since supplementation can lead to hypercalcemia and importantly, in vitro studies have shown that vitamin D3 influences the transcription of a gene that increases estrogen production.27,28 To assure that vitamin D3 does not abrogate the clinical effects of anti-estrogen therapies, the effect of vitamin D3 supplementation on estrogen production requires evaluation. Therefore, the overarching goal of this pilot study is to evaluate the safety, feasibility and efficacy of vitamin D3 supplementation in women with MBC. We will address and test the following aims and hypotheses, respectively:

Aim 1: To determine if weekly supplementation of 50,000 IUs of vitamin D3 raises serum levels of 25(OH)D to \>30 mg/dl without adverse effects.

Hypothesis 1: Women who are compliant with vitamin D3 supplementation, as evidenced by normalization (\>30 mg/dl) or increases in their serum 25(OH)D levels, will not experience significant changes in serum calcium, parathyroid hormone or serum estradiol levels.

Aim 2: To determine the effect of vitamin D3 supplementation on symptom management.

Hypothesis 2: Women who achieve serum concentrations of 25 (OH)D ≥30 mg/dl or experience significant increases in 25(OH)D will exhibit improvements in pain, fatigue, sleep, mood, muscle function and overall quality of life.

Exploratory Aim: To explore the mechanistic effects of vitamin D3 supplementation on inflammatory markers and its potential association with symptom management.

Summary: Evidence from studies involving early stage breast cancer participants confirms that musculoskeletal pain, endocrine related symptoms and mood disturbances are commonly associated with breast cancer treatment, particularly hormone deprivation therapies. The high prevalence of vitamin D deficiency/insufficiency among breast cancer survivors is well accepted and further hypothesized to aggravate treatment-related side effects, particularly arthralgias. Women with MBC are excluded from the majority of on-going vitamin D supplementation trials for safety and generalizability purposes. However, novel therapies are continuing to improve and prolong the lives of these women, resulting in a rapidly expansive group of breast cancer survivors. While vitamin D supplementation is prescribed to correct an underlying nutrient deficiency in the clinical context of preserving bone health, emerging evidence suggests it may have more systemic effects. Thus, vitamin D repletion/supplementation has profound potential implications for women with MBC, whose primary goal of treatment is to minimize the side-effects of treatment in support of optimal quality of life. This study reflects a highly innovative, yet simple therapy that could ultimately provide these survivors with a much needed evidence-based supportive care strategies.

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

Primary outcomes:
measure: Change in Serum 25(OH)D
timeFrame: 0, 8 weeks
Secondary outcomes:
measure: Change in Worst Pain Rating From the Beck Pain Scale
timeFrame: 0, 8 weeks
measure: Change in Fatigue
timeFrame: 0, 8 weeks
measure: Change in Mood
timeFrame: 0, 8 weeks
measure: Change in Muscle Function
timeFrame: 0, 8 weeks
measure: Change in Sleep Quality Assessment
timeFrame: 0, 8 weeks
measure: Change in Functional Assessment of Cancer Therapy-breast
timeFrame: 0, 8 weeks
measure: Change in Functional Assessment of Cancer Therapy-endocrine
timeFrame: 0, 8 weeks
Other outcomes:
Locations:
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
Study officials:
affiliation: Loyola University
name: Patricia M Sheean, Ph.D., R.D.
role: PRINCIPAL_INVESTIGATOR
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