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Zoledronic Acid in Aromatase Inhibitor Induced Musculoskeletal Symptoms

Primary Purpose

Ductal Carcinoma in Situ, Estrogen Receptor-positive Breast Cancer, Progesterone Receptor-positive Breast Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
letrozole
zoledronic acid
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Ductal Carcinoma in Situ

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria

  • Patients with histologically proven DCIS or stage I-III invasive carcinoma of the breast that is estrogen and/or progesterone receptor positive by immunohistochemical staining who are considering aromatase inhibitor therapy; women may receive the AI on this study as initial adjuvant hormonal treatment or following tamoxifen; patients must have completed any adjuvant chemotherapy; patients may have received preoperative chemotherapy
  • Postmenopausal status, defined as: >= 60 years of age; or < 60 years of age and amenorrheic for >= 12 months prior to day 1 if intact uterus/ovaries; or < 60 years of age, and the last menstrual period 6-12 months prior to day 1, if intact uterus/ovaries and meets biochemical criteria for menopause (FSH and estradiol within institutional standards for postmenopausal status); or < 60 years of age, without a uterus, and meets biochemical criteria for menopause (FSH and estradiol within institutional standards for postmenopausal status); or < 60 years of age and history of bilateral oophorectomy; or prior radiation castration with amenorrhea for at least 6 months; < 60 years of age and taking medication designed to suppress ovarian function and meets biochemical criteria for menopause (estradiol levels within institutional standards for postmenopausal status; women would have had to be taking the drug for at least 30 days prior to day 1)
  • ECOG performance status 0-2
  • Patient is aware of the nature of her diagnosis, understands the study regimen, its requirements, risks, and discomforts, and is able and willing to sign an informed consent form

Exclusion Criteria

  • Concurrent use of hormone replacement therapy
  • Concurrent use of tamoxifen; patients taking tamoxifen must discontinue the drug prior to first dose of zoledronic acid
  • Concurrent use of other selective estrogen receptor modulator (SERM) such as raloxifene
  • Concurrent consumption of soy supplements; routine dietary consumption of soy containing foods will be permitted
  • Prior use of an aromatase inhibitor in any setting
  • Current bisphosphonate use (oral or intravenous); prior bisphosphonate users would be eligible as long as the use was > 1 month ago for oral bisphosphonates and/or > 12 months ago for intravenous bisphosphonates, prior to starting study treatment
  • Moderate to severe renal impairment (serum creatinine greater than 2 mg/dL or creatinine clearance less than 50 mL/min)
  • Hypersensitivity to letrozole or zoledronic acid or any of its excipients
  • Concomitant treatment with oral or intravenous corticosteroids
  • Current active dental problems including infection or the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures
  • Recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants)

Sites / Locations

  • Johns Hopkins University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I - IV Zoledronic Acid Prophylaxis

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of Participants With Aromatase Inhibitor Associated Musculoskeletal Symptoms (AIMSS)

Secondary Outcome Measures

AIMSS as Determined by Health Assessment Questionnaire Disability Index (HAQ-DI) Score
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
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

Full Information

First Posted
August 31, 2010
Last Updated
August 14, 2018
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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1. Study Identification

Unique Protocol Identification Number
NCT01194440
Brief Title
Zoledronic Acid in Aromatase Inhibitor Induced Musculoskeletal Symptoms
Official Title
A Phase II Prospective Pilot Study Evaluating Efficacy of Intravenous Zoledronic Acid Prophylaxis for Prevention of Aromatase Inhibitor Associated Musculoskeletal Symptoms: ZAP-AIMSS Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
63 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I - IV Zoledronic Acid Prophylaxis
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
letrozole
Other Intervention Name(s)
CGS 20267, Femara, LTZ
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
zoledronic acid
Other Intervention Name(s)
CGP 42446, CGP42446A, NDC-zoledronate, ZOL 446, zoledronate, Zometa
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Number of Participants With Aromatase Inhibitor Associated Musculoskeletal Symptoms (AIMSS)
Time Frame
12 months
Secondary Outcome Measure Information:
Title
AIMSS as Determined by Health Assessment Questionnaire Disability Index (HAQ-DI) Score
Description
The HAQ-DI score ranges from 0-3 with a higher score reflective of greater disability or increased incidence of AIMSS.
Time Frame
Baseline, 1 month, 3 months, 6 months, 12 months
Title
AIMSS as Determined by Visual Analog Scale (VAS) Score
Description
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.
Time Frame
Baseline, 1 month, 3 months, 6 months, 12 months
Title
Number of Participants Who Discontinue or Change Aromatase Inhibitor (AI) Therapy
Time Frame
12 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Patients with histologically proven DCIS or stage I-III invasive carcinoma of the breast that is estrogen and/or progesterone receptor positive by immunohistochemical staining who are considering aromatase inhibitor therapy; women may receive the AI on this study as initial adjuvant hormonal treatment or following tamoxifen; patients must have completed any adjuvant chemotherapy; patients may have received preoperative chemotherapy Postmenopausal status, defined as: >= 60 years of age; or < 60 years of age and amenorrheic for >= 12 months prior to day 1 if intact uterus/ovaries; or < 60 years of age, and the last menstrual period 6-12 months prior to day 1, if intact uterus/ovaries and meets biochemical criteria for menopause (FSH and estradiol within institutional standards for postmenopausal status); or < 60 years of age, without a uterus, and meets biochemical criteria for menopause (FSH and estradiol within institutional standards for postmenopausal status); or < 60 years of age and history of bilateral oophorectomy; or prior radiation castration with amenorrhea for at least 6 months; < 60 years of age and taking medication designed to suppress ovarian function and meets biochemical criteria for menopause (estradiol levels within institutional standards for postmenopausal status; women would have had to be taking the drug for at least 30 days prior to day 1) ECOG performance status 0-2 Patient is aware of the nature of her diagnosis, understands the study regimen, its requirements, risks, and discomforts, and is able and willing to sign an informed consent form Exclusion Criteria Concurrent use of hormone replacement therapy Concurrent use of tamoxifen; patients taking tamoxifen must discontinue the drug prior to first dose of zoledronic acid Concurrent use of other selective estrogen receptor modulator (SERM) such as raloxifene Concurrent consumption of soy supplements; routine dietary consumption of soy containing foods will be permitted Prior use of an aromatase inhibitor in any setting Current bisphosphonate use (oral or intravenous); prior bisphosphonate users would be eligible as long as the use was > 1 month ago for oral bisphosphonates and/or > 12 months ago for intravenous bisphosphonates, prior to starting study treatment Moderate to severe renal impairment (serum creatinine greater than 2 mg/dL or creatinine clearance less than 50 mL/min) Hypersensitivity to letrozole or zoledronic acid or any of its excipients Concomitant treatment with oral or intravenous corticosteroids Current active dental problems including infection or the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures Recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vered Stearns
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287-8936
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://meetinglibrary.asco.org/record/93542/abstract
Description
General poster session - 2014 ASCO Annual Meeting

Learn more about this trial

Zoledronic Acid in Aromatase Inhibitor Induced Musculoskeletal Symptoms

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