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Zoledronic Acid in Aromatase Inhibitor Induced Musculoskeletal Symptoms

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01194440
First received: August 31, 2010
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
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
Drug: letrozole
Drug: zoledronic acid
Other: laboratory biomarker analysis
Other: enzyme-linked immunosorbent assay
Other: mass spectrometry
Procedure: bone scan
Procedure: quality-of-life assessment
Other: questionnaire administration
Other: pharmacogenomic studies
Other: high performance liquid chromatography
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
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

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Frequency of women with aromatase inhibitor associated musculoskeletal symptoms (AIMSS) [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Health Assessment Questionnaire Disability Index [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Visual analog scale [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Amount and/or frequency of oral analgesic [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Menopausal symptoms [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Hot flash frequency [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Plasma estrogen concentrations [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Mineral density as assessed by DEXA scan [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Bone turn over markers (serum-C telopeptide, bone-specific alkaline phosphatase, osteocalcin and urinary N-telopeptide) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Inflammatory markers (ESR, CRP, IL-1, IL-6, IL-8) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Number of patients who discontinue or change aromatase inhibitory (AI) therapy [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 59
Study Start Date: February 2011
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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.
Drug: letrozole
Given orally
Other Names:
  • CGS 20267
  • Femara
  • LTZ
Drug: zoledronic acid
Given IV
Other Names:
  • CGP 42446
  • CGP42446A
  • NDC-zoledronate
  • ZOL 446
  • zoledronate
  • Zometa
Other: laboratory biomarker analysis
Correlative studies
Other: enzyme-linked immunosorbent assay
Correlative studies
Other Name: ELISA
Other: mass spectrometry
Correlative studies
Procedure: bone scan
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: questionnaire administration
Ancillary studies
Other: pharmacogenomic studies
Correlative studies
Other Name: Pharmacogenomic Study
Other: high performance liquid chromatography
Correlative studies
Other Name: HPLC

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion

  • 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

  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01194440

Locations
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8936
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Vered Stearns Johns Hopkins University
  More Information

No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01194440     History of Changes
Other Study ID Numbers: J1022, SKCCC J1022
Study First Received: August 31, 2010
Last Updated: May 12, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma in Situ
Carcinoma, Ductal
Carcinoma, Ductal, Breast
Carcinoma, Intraductal, Noninfiltrating
Adenocarcinoma
Breast Diseases
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Ductal, Lobular, and Medullary
Neoplasms, Glandular and Epithelial
Skin Diseases
Aromatase Inhibitors
Diphosphonates
Letrozole
Zoledronic acid
Antineoplastic Agents
Bone Density Conservation Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014