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

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

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

Study Overview

• Status: Completed
• Conditions: Pain; Arthralgia; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Recurrent Breast Cancer; Musculoskeletal Complications
• Intervention / Treatment: Drug: letrozole; Procedure: assessment of therapy complications; Other: laboratory biomarker analysis; Dietary supplement: calcium carbonate; Dietary supplement: calcium citrate; Dietary supplement: calcium glucarate; Drug: calcium gluconate; Dietary supplement: cholecalciferol; Procedure: musculoskeletal complications management/prevention

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (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.

Drug: letrozole; Given PO; Other Names: CGS 20267; Femara; LTZ; Procedure: assessment of therapy complications; Ancillary studies; Other: laboratory biomarker analysis; Optional correlative studies; Dietary supplement: calcium carbonate; Given PO; Other Names: CaCO3; Dietary supplement: calcium citrate; Given PO; Other Names: Citracal; Acicontral; CALCIT; Tricalcium Citrate; Dietary supplement: calcium glucarate; Given PO; Other Names: antacidin; calcium D-glucarate; calcium D-saccharate; CGT; Drug: calcium gluconate; Given PO; Other Names: Calcium D-gluconate; CALGLUC; Calglucon; Dietary supplement: cholecalciferol; Given PO; Other Names: Vitamin D3; Calciol; Procedure: musculoskeletal complications management/prevention; Correlative studies; Other Names: complications management/prevention, musculoskeletal; management/prevention, musculoskeletal complications

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: December 27, 2006
• First Submitted That Met QC Criteria: December 27, 2006
• First Posted (Estimate): December 28, 2006

Study Record Updates

• Last Update Posted (Actual): July 11, 2017
• Last Update Submitted That Met QC Criteria: June 10, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Pain; Neurologic Manifestations; Breast Diseases; Nutrition Disorders; Joint Diseases; Musculoskeletal Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Breast Neoplasms; Arthralgia; Vitamin D Deficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Gastrointestinal Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Micronutrients; Hormone Antagonists; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Anticoagulants; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Chelating Agents; Sequestering Agents; Calcium Chelating Agents; Antacids; Vitamin D; Cholecalciferol; Letrozole; Calcium; Calcium, Dietary; Calcium Carbonate; Citric Acid; Sodium Citrate
• Other Study ID Numbers: 6346; NCI-2010-00621 (Registry Identifier: CTRP (Clinical Trial Reporting Program))