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

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT00416715
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 100
• Location: 1
• Arm: 1
• Duration (Months): 43
• Patients Per Site Per Month: 2.3

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
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	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	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. To determine if there is a correlation between letrozole serum levels and the development of myalgias, arthralgias and/or joint stiffness.

2. 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 Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Pilot Study of Vitamin D Deficiency and Myalgias, Arthralgias and/or Joint Stiffness Associated With Letrozole (Femara® )
• Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

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 ; Dietary Supplement: calcium carbonate; Given PO; Other Names: CaCO3 ; Other: laboratory biomarker analysis; Optional correlative studies; Dietary Supplement: calcium citrate; Given PO; Other Names: Acicontral CALCIT Citracal 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: Calciol Vitamin D3 ; Procedure: assessment of therapy complications; Ancillary studies; Procedure: musculoskeletal complications management/prevention; Correlative studies; Other Names: complications management/prevention, musculoskeletal management/prevention, musculoskeletal complications

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• University of Washington
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Hannah Linden, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hannah Linden, Principal Investigator, University of Washington
• ClinicalTrials.gov Identifier: NCT00416715
• Other Study ID Numbers: 6346; NCI-2010-00621
• First Posted: Dec 28, 2006
• Last Update Posted: Jul 11, 2017
• Last Verified: Jun 1, 2017

• Additional relevant MeSH terms: Breast Neoplasms; Arthralgia; Vitamin D Deficiency; Calcium, Dietary; Vitamin D; Cholecalciferol; Letrozole; Calcium Carbonate; Citric Acid; Sodium Citrate; Calcium

Study Results

Participant Flow

Arm/Group Title	Treatment (Letrozole)
Arm/Group Description	Patients receive letrozole PO QD. Patients, who experience muscle pain, joint pain, or joint stiffness 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. letrozole: Given PO calcium carbonate: Given PO laboratory biomarker analysis: Optional correlative studies calcium citrate: Given PO calcium glucarate: Given PO calcium gluconate: Given PO cholecalciferol: Given PO assessment of therapy complications: Ancillary studies musculoskeletal complications management/prevention: Correlative studies
Period Title: Overall Study
STARTED	100
COMPLETED	85
NOT COMPLETED	15

Baseline Characteristics

Arm/Group Title	Treatment (Letrozole)
Arm/Group Description	Patients receive letrozole PO QD. Patients, who experience muscle pain, joint pain, or joint stiffness 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. letrozole: Given PO calcium carbonate: Given PO laboratory biomarker analysis: Optional correlative studies calcium citrate: Given PO calcium glucarate: Given PO calcium gluconate: Given PO cholecalciferol: Given PO assessment of therapy complications: Ancillary studies musculoskeletal complications management/prevention: Correlative studies
Overall Participants	100
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56
Sex: Female, Male (Count of Participants)
Female	100 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 2%
Not Hispanic or Latino	98 98%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 2%
White	87 87%
More than one race	3 3%
Unknown or Not Reported	5 5%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline	Post Vitamin D Repletion (1 Month)
Arm/Group Description	All patients that are evaluable for joint aches and vitamin D levels.	Patients with vitamin D deficiency who experience myalgias, arthralgias and/or joint stiffness.
Measure Participants	85	12
Count of Participants [Participants]	12 12%	1 NaN

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Only considering those patients who were baseline vitamin D deficient and experienced myalgias, arthralgias and/or joint stiffness.

Arm/Group Title	Baseline	Post Vitamin D Repletion (1 Month)
Arm/Group Description	Those receiving Letrozole + vitamin D3	Those receiving Letrezole + vitamin D3
Measure Participants	12	12
Median (Inter-Quartile Range) [micro-grams/mL]	85	70

Adverse Events

Arm/Group Title	Treatment (Letrezole)
Arm/Group Description	Patients receive letrozole PO QD. Patients, who experience muscle pain, joint pain, or joint stiffness 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. letrozole: Given PO calcium carbonate: Given PO laboratory biomarker analysis: Optional correlative studies calcium citrate: Given PO calcium glucarate: Given PO calcium gluconate: Given PO cholecalciferol: Given PO assessment of therapy complications: Ancillary studies musculoskeletal complications management/prevention: Correlative studies
All Cause Mortality
	Treatment (Letrezole)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Letrezole)
	Affected / at Risk (%)	# Events
Total	0/100 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (Letrezole)
	Affected / at Risk (%)	# Events
Total	27/100 (27%)
General disorders
Joint aches	27/100 (27%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.