Zoledronic Acid in Aromatase Inhibitor Induced Musculoskeletal Symptoms

Phase 2

Completed

• Conditions: Ductal Carcinoma in Situ; Estrogen Receptor-positive Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer
• Interventions: Drug: letrozole; Drug: zoledronic acid

• Registration Number: NCT01194440
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary

RATIONALE: Zoledronic acid may prevent bone loss and help prevent or lessen musculoskeletal symptoms in women receiving hormone therapy for breast cancer.

PURPOSE: This phase II trial is studying how well zoledronic acid works in preventing musculoskeletal symptoms in post-menopausal women with stage I, stage II, or stage III breast cancer receiving letrozole.

Detailed Description

PRIMARY OBJECTIVES:

I. Percentage of women experiencing aromatase inhibitor associated musculoskeletal symptoms (AIMSS) at 1, 3, 6, and 12 months after bisphosphonate therapy, as compared to historical controls.

II. Change in Health Assessment Questionnaire Disability Index (HAQ-DI) score and 1, 3, 6 and 12 months, from baseline, among those receiving bisphosphonate, as compared to historical controls.

SECONDARY OBJECTIVES:

I. Change in pain scores on visual analog scale (VAS) at 1, 3, 6 and 12 months, from baseline, compared to historical controls.

II. Change in amount and/or frequency of oral analgesic use at 1, 3, 6 and 12 months from baseline among those receiving bisphosphonate therapy, as compared to historical controls.

III. Number of patients who discontinue or change aromatase inhibitor (AI) therapy.

IV. Change in menopausal symptoms (NSABP-revised), hot flash frequency (HFRDIS),sleep quality (PSQI), depression score (CESD) and overall quality of life (EuroQOL) in patients at 1, 3, 6 and 12 months from baseline, among those receiving bisphosphonate therapy, as compared to historical controls.

V. Changes in plasma estrogen concentrations at 1, 3, 6 and 12 months from baseline, among those receiving bisphosphonate therapy, as compared to historical controls.

VI. Change in bone mineral density (DEXA scan) at 12 months from baseline, among those receiving bisphosphonate therapy, as compared to historical controls.

VII. Change in bone turn over markers (serum-C telopeptide, bone-specific alkaline phosphatase, osteocalcin and urinary N-telopeptide) at 1, 3, 6 and 12 months from baseline, among those receiving bisphosphonate therapy, as compared to historical controls.

VIII. Change in inflammatory markers (ESR, CRP, IL-1, IL-6, IL-8) at 1, 3, 6 and 12 months from baseline, among those receiving bisphosphonate therapy, as compared to historical controls.

OUTLINE: Patients receive zoledronic acid intravenously (IV) at months 1 and 6. Beginning 14 days after first zoledronic acid infusion, patients receive oral letrozole once daily for 12 months in the absence of disease progression or unacceptable toxicity.

Study Timeline

• Study First Submitted: 2010-08-31
• Study First Submitted QC: 2010-09-01
• Study First Posted: 2010-09-03
• Study Start: 2011-02
• Primary Completion: 2014-01
• Study Completion: 2014-01
• Results First Submitted: 2016-11-10
• Results First Submitted QC: 2016-11-10
• Results First Posted: 2017-01-09
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-14
• Last Update Posted: 2018-09-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 63

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I - IV Zoledronic Acid Prophylaxis	zoledronic acid	Patients receive zoledronic acid IV at months 1 and 6. Beginning 14 days after first zoledronic acid infusion, patients receive oral letrozole once daily for 12 months in the absence of disease progression or unacceptable toxicity.
Arm I - IV Zoledronic Acid Prophylaxis	letrozole	Patients receive zoledronic acid IV at months 1 and 6. Beginning 14 days after first zoledronic acid infusion, patients receive oral letrozole once daily for 12 months in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Aromatase Inhibitor Associated Musculoskeletal Symptoms (AIMSS)	12 months

Secondary Outcome Measures

Name	Time	Method
AIMSS as Determined by Health Assessment Questionnaire Disability Index (HAQ-DI) Score	Baseline, 1 month, 3 months, 6 months, 12 months	The HAQ-DI score ranges from 0-3 with a higher score reflective of greater disability or increased incidence of AIMSS.
AIMSS as Determined by Visual Analog Scale (VAS) Score	Baseline, 1 month, 3 months, 6 months, 12 months	VAS is a visual measurement tool to assess AIMSS. It is a visual scale that ranges from 0 centimeters (cm) to 10cm. The VAS score ranges from zero (0cm) to 10 (10cm), with a higher score reflecting a greater frequency of AIMSS.
Number of Participants Who Discontinue or Change Aromatase Inhibitor (AI) Therapy	12 months

Trial Locations

Locations (1)

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States