Breast Cancer
Conditions
Keywords
Breast Cancer, Hormone Receptor Positive, Vitamin D
Brief summary
This study is being done to look at the difference, if there is a difference between two different doses of Vitamin D and the reduction of joint/muscle pain (arthralgia)that is caused by taking anti-estrogen medications (aromatase inhibitors) by breast cancer patients. The investigators hope to learn if taking a higher dose of Vitamin D is a good way to prevent aromatase inhibitor arthralgia (AIA).
Detailed description
Treatments with anti-estrogen agents for hormone receptor positive breast cancer is the most efficacious of systemic therapies, with aromatase inhibitors (AI's) being considered the most active anti-estrogen therapy in early stage breast cancer. But, use of these treatments has been shown to cause musculoskeletal (joint/muscle) side effects that sometimes cause patients to discontinue the use of them. Also, Vitamin D deficiency is a well know cause of a wide array of musculoskeletal issues. There is evidence that Vitamin D supplementation may help prevent arthralgia while on AI's. Therefore, the investigators want to see if giving a higher dose of Vitamin D could decrease the incidence of AIA as compared to a standard dose of Vitamin D. The investigators believe that this could possibly result in patients continued treatment with AI therapy for hormone receptor positive breast cancer.
Interventions
DRUG800 IU Vitamin D Supplement
Standard Dose
DRUG50,000 IU Vitamin D supplement
High Dose
Sponsors
Mothaffar Rimawi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All participants must be female and at least 21 years of age * Signed informed consent * Patients must have had histologically confirmed stage I-III breast carcinoma that is positive for Estrogen Receptor (ER) and/or Progesterone Receptor (PR). * Post-menopausal * Beginning adjuvant aromatase inhibitor therapy, with no previous use within the last 6 weeks * Bisphosphonates are allowed at the treating investigator¡¦s discretion * Performance status (WHO/ECOG scale) 0-2.
Exclusion criteria
* History of kidney stones * Hypercalcemia at baseline, defined as any corrected calcium greater than the laboratory's normal parameters * History of either symptomatic hypercalcemia or hyperparathyroidism, at the treating investigator's discretion * Baseline Vitamin D level greater than 50 ng/mL * Inability or unwillingness to comply with, or follow study procedures. * Currently taking Phenytoin or phenobarbital -7 Currently taking cholestyramine or orlistat * Malabsorption syndrome, such as Crohn's disease Prohibited Therapies: Patients may not take additional Calcium and Vitamin D aside from the study medications. Patients who are on cholestyramine or orlistat will not be allowed on the trial. Also, patients who are taking phenytoin or phenobarbital are not allowed on the trial either because of interaction between Vitamin D and anti-epileptic medications.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Aromatase Inhibitor Induced Arthralgia (AIA) After 12 Weeks of Therapy | 12 weeks | Aromatase Inhibitor Arthralgia (AIA) was assessed by a questionnaire that describe the level of pain experienced by the participant. The questionnaire asks 20 questions scored 0-3 in 8 categories of functioning: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. An average composite score on the HAQ-II was calculated. The visual analog scale is the other major component of the HAQ-II, which we ask patients to mark where their pain lies on a horizontal line and we converts the number into a score from 0 to 3. For the purposes of this study, AIA will be defined as any of the following criteria: 1) increase in HAQ-II score from baseline by 0.2 or greater; or 2) increase in visual analog pain score by 0.3 or greater. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compliance With Anti-Cancer Treatment | 52 Weeks | We checked compliance of aromatase inhibitor therapy during the study by reviewing the patient's use of AI drug. This will be done by counting remaining pills in patient's bottles of AI at 52 weeks. A percentage of the number of pills were actually taken of the number of pills should be taken was calculated. |
| Association Between Vitamin D Levels Changes and Treatment. | 12 weeks | Patients' serum 25-hydroxyvitamin D level were tested at baseline and week 12. The changes between baseline and week 12 were calculated. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Grip Strength | 52 weeks | Exploratory Endpoints For each patient on the study, grip strength will be correlated with AIA score using Spearman correlation at three time points throughout the study - baseline, week 12, and week 52. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High Dose Vitamin D ARM 50,000 IU Vitamin D supplement
50,000 IU Vitamin D supplement: High Dose | 46 |
| 800 IU Vitamin D Supplement 800 IU Vitamin D Supplement
800 IU Vitamin D Supplement: Standard Dose | 47 |
| Total | 93 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Complete Study After Start | Protocol Violation | 1 | 1 |
| Complete Study After Start | Withdrawal by Subject | 2 | 0 |
| Start Treament After Randomization | Protocol Violation | 0 | 1 |
| Start Treament After Randomization | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | High Dose Vitamin D ARM | Total | 800 IU Vitamin D Supplement |
|---|---|---|---|
| Age, Continuous | 62.9 years STANDARD_DEVIATION 7 | 63.4 years STANDARD_DEVIATION 7.8 | 63.8 years STANDARD_DEVIATION 8.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 41 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 50 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 17 Participants | 6 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 | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) White | 33 Participants | 72 Participants | 39 Participants |
| Region of Enrollment United States | 46 participants | 93 participants | 47 participants |
| Serum 25-hydroxyvitamin D level | 21.7 ng/mL STANDARD_DEVIATION 8.7 | 23 ng/mL STANDARD_DEVIATION 8 | 24.2 ng/mL STANDARD_DEVIATION 7.1 |
| Sex: Female, Male Female | 46 Participants | 93 Participants | 47 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 | 0 / 44 | 0 / 43 |
| other Total, other adverse events | 35 / 44 | 36 / 43 |
| serious Total, serious adverse events | 2 / 44 | 0 / 43 |
Outcome results
Primary
Number of Participants With Aromatase Inhibitor Induced Arthralgia (AIA) After 12 Weeks of Therapy
Aromatase Inhibitor Arthralgia (AIA) was assessed by a questionnaire that describe the level of pain experienced by the participant. The questionnaire asks 20 questions scored 0-3 in 8 categories of functioning: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. An average composite score on the HAQ-II was calculated. The visual analog scale is the other major component of the HAQ-II, which we ask patients to mark where their pain lies on a horizontal line and we converts the number into a score from 0 to 3. For the purposes of this study, AIA will be defined as any of the following criteria: 1) increase in HAQ-II score from baseline by 0.2 or greater; or 2) increase in visual analog pain score by 0.3 or greater.
Time frame: 12 weeks
Population: ITT population. All patients who were randomized in the study were included in the overall evaluation of response (intent-to-treat analysis).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Dose Vitamin D ARM | Number of Participants With Aromatase Inhibitor Induced Arthralgia (AIA) After 12 Weeks of Therapy | development of AIA | 25 Participants |
| High Dose Vitamin D ARM | Number of Participants With Aromatase Inhibitor Induced Arthralgia (AIA) After 12 Weeks of Therapy | no development of AIA | 21 Participants |
| 800 IU Vitamin D Supplement | Number of Participants With Aromatase Inhibitor Induced Arthralgia (AIA) After 12 Weeks of Therapy | development of AIA | 27 Participants |
| 800 IU Vitamin D Supplement | Number of Participants With Aromatase Inhibitor Induced Arthralgia (AIA) After 12 Weeks of Therapy | no development of AIA | 20 Participants |
p-value: 0.7635Chi-squared
Secondary
Association Between Vitamin D Levels Changes and Treatment.
Patients' serum 25-hydroxyvitamin D level were tested at baseline and week 12. The changes between baseline and week 12 were calculated.
Time frame: 12 weeks
Population: Patients who had serum 25-hydroxyvitamin D level tested at baseline and week 12 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose Vitamin D ARM | Association Between Vitamin D Levels Changes and Treatment. | 28.8 ng/mL | Standard Deviation 14.5 |
| 800 IU Vitamin D Supplement | Association Between Vitamin D Levels Changes and Treatment. | 5.2 ng/mL | Standard Deviation 7.3 |
p-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
Compliance With Anti-Cancer Treatment
We checked compliance of aromatase inhibitor therapy during the study by reviewing the patient's use of AI drug. This will be done by counting remaining pills in patient's bottles of AI at 52 weeks. A percentage of the number of pills were actually taken of the number of pills should be taken was calculated.
Time frame: 52 Weeks
Population: Compliance was assessed at week 52. Only 14 patients have compete the data collection.~Form was not completed due to not starting the treatment, or not finishing the treatment, or no source data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose Vitamin D ARM | Compliance With Anti-Cancer Treatment | 0.981 percentage of pills taken | Standard Deviation 0.047 |
| 800 IU Vitamin D Supplement | Compliance With Anti-Cancer Treatment | 0.965 percentage of pills taken | Standard Deviation 0.07 |
Other Pre-specified
Grip Strength
Exploratory Endpoints For each patient on the study, grip strength will be correlated with AIA score using Spearman correlation at three time points throughout the study - baseline, week 12, and week 52.
Time frame: 52 weeks