Breast Cancer
Conditions
Brief summary
The primary purpose is to determine if high dose vitamin D3 reduces the incidence of musculoskeletal symptoms associated with the aromatase inhibitor letrozole in women with early stage breast cancer and low serum vitamin D levels.
Detailed description
The primary hypothesis is that high dose vitamin D3 plus standard dose vitamin D3 prevents the worsening of musculoskeletal symptoms when compared to a standard dose vitamin D3 treatment. This protocol will examine the relationship between vitamin D levels (25-hydroxyvitamin D) and various quality of life measures in women being treated with letrozole as standard care for early stage breast cancer. All subjects received letrozole and a standard dose of vitamin D3 (600 IU daily). Randomization was between high dose vitamin D3 (30,000 IU once per week) vs. a blinded, matched placebo,
Interventions
DIETARY_SUPPLEMENTHigh Dose Vitamin D
High Dose Vitamin D3 (3 capsules of 10,000 IU) weekly for 24 weeks.
DIETARY_SUPPLEMENTPlacebo
Placebo comparator
DIETARY_SUPPLEMENTStandard Dose Vitamin D3
Standard Dose Vitamin D3 (600 IU of vitamin D3 daily)
DRUGLetrozole 2.5mg
All subjects received letrozole as standard of care.
Sponsors
Novartis Pharmaceuticals
BTR Group
Qamar Khan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Post-menopausal women newly diagnosed with early stage breast cancer, who would be treated with an aromatase inhibitor * Serum 25OHD levels \< 40 ng/ml
Exclusion criteria
* Severe or debilitating musculoskeletal pain * Known metastatic disease * History of renal stones * History of hypercalcemia or hyperthyroidism * Currently receiving adjuvant or neoadjuvant chemotherapy * Currently receiving other investigational agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Worsening of Musculoskeletal Symptoms (MS) | Change from Baseline to 24 Weeks | Worsening of Musculoskeletal Symptoms (MS) is defined as any one of the following three events: (a) an increase by at least 0.25 in the Health Assessment Questionnaire II (HAQ II, a measure of disability from joint pain) score, (b) an increase in patient reported severity of joint and/or muscle pain, or (c) discontinuation from trial prior to 24 weeks specifically because of problems with musculoskeletal symptoms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo (3 capsules of matching placebo weekly) along with standard of care medication (Standard Dose Vitamin D3, 600 IU of vitamin D3 daily; letrozole, 2.5 mg daily) for 24 weeks. | 80 |
| Vitamin D High Dose Vitamin D3 (3 capsules of 10,000 IU weekly) along with standard of care medication (Standard Dose Vitamin D3, 600 IU of vitamin D3 daily; letrozole, 2.5 mg daily) for 24 weeks. | 80 |
| Total | 160 |
Baseline characteristics
| Characteristic | Placebo | Total | Vitamin D |
|---|---|---|---|
| Age, Customized | 62 years | 62 years | 60.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 75 Participants | 152 Participants | 77 Participants |
| Region of Enrollment United States | 80 participants | 160 participants | 80 participants |
| Sex: Female, Male Female | 80 Participants | 160 Participants | 80 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 67 / 80 | 37 / 80 |
| serious Total, serious adverse events | 3 / 80 | 3 / 80 |
Outcome results
Primary
Number of Participants With Worsening of Musculoskeletal Symptoms (MS)
Worsening of Musculoskeletal Symptoms (MS) is defined as any one of the following three events: (a) an increase by at least 0.25 in the Health Assessment Questionnaire II (HAQ II, a measure of disability from joint pain) score, (b) an increase in patient reported severity of joint and/or muscle pain, or (c) discontinuation from trial prior to 24 weeks specifically because of problems with musculoskeletal symptoms.
Time frame: Change from Baseline to 24 Weeks
Population: Subjects available for analysis included those that had completed the entire study; plus three subjects that had dropped out early specifically because of side effects related to musculoskeletal symptoms (one of the endpoints).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Worsening of Musculoskeletal Symptoms (MS) | HAQ II increase by 0.25 | 23 participants |
| Placebo | Number of Participants With Worsening of Musculoskeletal Symptoms (MS) | Subjective Pain increase | 24 participants |
| Placebo | Number of Participants With Worsening of Musculoskeletal Symptoms (MS) | Discontinuation due to AEs | 3 participants |
| Placebo | Number of Participants With Worsening of Musculoskeletal Symptoms (MS) | Any of the three measures | 39 participants |
| Vitamin D | Number of Participants With Worsening of Musculoskeletal Symptoms (MS) | Any of the three measures | 26 participants |
| Vitamin D | Number of Participants With Worsening of Musculoskeletal Symptoms (MS) | HAQ II increase by 0.25 | 18 participants |
| Vitamin D | Number of Participants With Worsening of Musculoskeletal Symptoms (MS) | Discontinuation due to AEs | 0 participants |
| Vitamin D | Number of Participants With Worsening of Musculoskeletal Symptoms (MS) | Subjective Pain increase | 18 participants |