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

August 31, 2010
May 12, 2014
February 2011
January 2014   (final data collection date for primary outcome measure)
Frequency of women with aromatase inhibitor associated musculoskeletal symptoms (AIMSS) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01194440 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Zoledronic Acid in Aromatase Inhibitor Induced Musculoskeletal Symptoms
A Phase II Prospective Pilot Study Evaluating Efficacy of Intravenous Zoledronic Acid Prophylaxis for Prevention of Aromatase Inhibitor Associated Musculoskeletal Symptoms: ZAP-AIMSS Trial

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.

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
  • 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
    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
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.
Interventions:
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
59
January 2014
January 2014   (final data collection date for primary outcome measure)

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)
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01194440
J1022, SKCCC J1022
No
Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
Not Provided
Principal Investigator: Vered Stearns Johns Hopkins University
Sidney Kimmel Comprehensive Cancer Center
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP