Safety, Feasibility and Efficacy of Vitamin D Supplementation in Women With Metastatic Breast Cancer (SAFE-D)
| Status: | Completed |
|---|---|
| Conditions: | Breast Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 9/30/2018 |
| Start Date: | February 2015 |
| End Date: | November 9, 2017 |
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 important 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 (e.g., pain, sleep, fatigue, mood, and overall quality
of life) will be assessed at baseline, 4 and 8 weeks post-supplementation. We will assess if
increases in vitamin D are associated with clinically significant changes in serum estradiol,
improvements in symptoms and QOL, and decreased inflammation, controlling for sunlight
exposure, diet, physical activity and body composition.
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 important 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 (e.g., pain, sleep, fatigue, mood, and overall quality
of life) will be assessed at baseline, 4 and 8 weeks post-supplementation. We will assess if
increases in vitamin D are associated with clinically significant changes in serum estradiol,
improvements in symptoms and QOL, and decreased inflammation, controlling for sunlight
exposure, diet, physical activity and body composition.
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.
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.
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
We found this trial at
1
site
2160 South 1st Avenue
Maywood, Illinois 60153
Maywood, Illinois 60153
(888) 584-7888
Principal Investigator: Patricia M Sheean, Ph.D., R.D.
Phone: 708-216-0344
Loyola University Medical Center Loyola University Health System is committed to excellence in patient care...
Click here to add this to my saved trials
