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

Phase 2

Completed

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

Interventions: 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

Registration Number: NCT00416715

Lead Sponsor: University of Washington

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 100

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (letrozole)	letrozole	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.
Treatment (letrozole)	calcium carbonate	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.
Treatment (letrozole)	laboratory biomarker analysis	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.
Treatment (letrozole)	calcium citrate	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.
Treatment (letrozole)	calcium glucarate	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.
Treatment (letrozole)	calcium gluconate	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.
Treatment (letrozole)	cholecalciferol	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.
Treatment (letrozole)	assessment of therapy complications	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.
Treatment (letrozole)	musculoskeletal complications management/prevention	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.

Primary Outcome Measures

Name	Time	Method
Number of Early Breast Cancer Patients Prescribed Adjuvant Letrozole That Are Vitamin D Deficient and Who Experience Myalgias, Arthralgias and/or Joint Stiffness	Baseline and 1 month post vitamin D repletion	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.

Secondary Outcome Measures

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