Vitamin D Deficiency, Muscle Pain, Joint Pain, and Joint Stiffness in Postmenopausal Women Receiving Letrozole For Stage I-III Breast Cancer

Study Overview
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Brief Summary
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This phase II trial is studying vitamin D deficiency, muscle pain, joint pain, and joint stiffness in postmenopausal women receiving letrozole for stage I-III breast cancer. Learning about vitamin D deficiency and muscle pain, joint pain, and joint stiffness in patients receiving letrozole for breast cancer may help doctors plan treatment and may help patients live more comfortably

Detailed Description
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PRIMARY OBJECTIVES: I. To assess the rate of vitamin D deficiency in breast cancer patients who experience myalgias, arthralgias and/or joint stiffness following initiation of adjuvant letrozole treatment. SECONDARY OBJECTIVES: I. To determine if there is a correlation between letrozole serum levels and the development of myalgias, arthralgias and/or joint stiffness. II. To assess if vitamin D supplementation may alleviate myalgias, arthralgias and/or joint stiffness associated with letrozole in those subjects with vitamin D deficiency. OUTLINE: Patients receive letrozole orally (PO) once daily (QD). Patients, who experience muscle pain, joint pain, or joint stiffness that requires an intervention and who are found to be vitamin D deficient, also receive calcium PO and vitamin D3 PO. Treatment continues for up to 28 weeks in the absence of disease progression or unacceptable toxicity.

Official Title
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A Pilot Study of Vitamin D Deficiency and Myalgias, Arthralgias and/or Joint Stiffness Associated With Letrozole (Femara® )

Conditions
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Arthralgia, Musculoskeletal Complications, Pain, Recurrent Breast Cancer, Stage I Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer

Intervention / Treatment
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* Drug: letrozole
* Dietary Supplement: calcium carbonate
* Other: laboratory biomarker analysis
* Dietary Supplement: calcium citrate
* Dietary Supplement: calcium glucarate
* Drug: calcium gluconate
* Dietary Supplement: cholecalciferol
* Procedure: assessment of therapy complications
* Procedure: musculoskeletal complications management/prevention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a histologically confirmed diagnosis of Stage I, II or III breast carcinoma Patients must be prescribed letrozole for adjuvant breast cancer treatment Prior adjuvant tamoxifen is permitted Patients must be postmenopausal; for study purposes, postmenopausal is defined as: a prior documented bilateral oophorectomy, or a history of at least 12 months without spontaneous menstrual bleeding, or have a persistently postmenopausal estradiol in the past 6 months without menses, and clinically in menopause at the judgment of the treating physician, or age 60 or older with a prior hysterectomy without oophorectomy, or age less than 60 with a prior hysterectomy without oophorectomy (or in whom the status of the ovaries is unknown), with a documented FSH level demonstrating confirmatory elevation in the postmenopausal range for the lab Exclusion Criteria: Diagnosis of Stage IV breast carcinoma Pre-existing myalgias, arthralgias and/or joint stiffness >= Grade 1, as defined using CTEP CTC identified during baseline physical exam Inability to understand or cooperate with study procedures Receipt of investigational drug within 30 days before study entry Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome Unwillingness to give informed consent Unwillingness to participate or inability to comply with the protocol for the duration of the study Patients with serum calcium >= 14 mg/dL Patients with renal dysfunction defined as glomerular filtration rate <10ml/min calculated using Cockroft-Gault equation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (letrozole)<br>Patients receive letrozole PO QD. Patients, who experience muscle pain, joint pain, or joint stiffness that requires an intervention and who are found to be vitamin D deficient, also receive calcium and vitamin D3 PO. Treatment continues for up to 28 weeks in the absence of disease progression or unacceptable toxicity. | Drug: letrozole<br>* Given PO<br>* Other names: LTZ;Dietary Supplement: calcium carbonate<br>* Given PO<br>* Other names: CaCO3;Other: laboratory biomarker analysis<br>* Optional correlative studies<br>Dietary Supplement: calcium citrate<br>* Given PO<br>* Other names: Tricalcium Citrate;Dietary Supplement: calcium glucarate<br>* Given PO<br>* Other names: CGT;Drug: calcium gluconate<br>* Given PO<br>* Other names: Calglucon;Dietary Supplement: cholecalciferol<br>* Given PO<br>* Other names: Vitamin D3;Procedure: assessment of therapy complications<br>* Ancillary studies<br>Procedure: musculoskeletal complications management/prevention<br>* Correlative studies<br>* Other names: management/prevention, musculoskeletal complications;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Early Breast Cancer Patients Prescribed Adjuvant Letrozole That Are Vitamin D Deficient and Who Experience Myalgias, Arthralgias and/or Joint Stiffness | Count of early breast cancer patients prescribed adjuvant letrozole that are vitamin D deficient and who experience myalgias, arthralgias and/or joint stiffness, assessed at baseline and 1 month after vitamin D repletion. | Baseline and 1 month post vitamin D repletion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Letrozole Serum Levels Before and After Vitamin D Repletion | Letrezole serum level concentration in patients that were vitamin D deficient and experienced myalgias, arthralgias and/or joint stiffness. | Baseline and 1 month post vitamin D repletion |