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The Safety and Efficacy of Zoledronic Acid in the Prevention of Cancer Therapy Induced Bone Loss

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00375505
First received: September 11, 2006
Last updated: August 11, 2015
Last verified: August 2015
  Purpose
This study examines the safety and efficacy of zoledronic acid 4 mg., given every 3 months over 24 months (infusion at month 0, 3, 6, 9, 12, 15, 18 and 21) in improving bone mineral density in premenopausal women with hormone receptor negative breast cancer and adjuvant chemotherapeutic treatment

Condition Intervention Phase
Breast Cancer
Drug: Zoledronic acid
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Zoledronic Acid in the Prevention of Cancer Therapy Induced Bone Loss

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change in Bone Mineral Density (BMD) Measured by Dual (Energy) X-ray Absorptiometry (DXA) at Lumbar Spine (L2-L4) From Baseline to Month 24 [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    Bone mineral density (BMD) by DXA at lumbar spine (L2-L4); DXA assessments of the BMD at dual hips. (BMD). Two X-ray beams with different energy levels are aimed at the patient's bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone.

  • Change in Bone Mineral Density (BMD) at Lumbar Spine (L2-L4) From Baseline to Month 24 or Last Visit Measure by T-score [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    Bone mineral density (BMD) at lumbar spine (L2-L4) by T-score. Your T-score is the number of units that your bone density is above or below the average. -1 and above-bone density is considered normal; Between -1 and -2.5-is a sign of osteopenia, a condition in which bone density is below normal and may lead to osteoporosis. -2.5 and below-indicates that it is likely osteoporosis.

  • Change in Bone Mineral Density (BMD) at Lumbar Spine (L2-L4) From Baseline to Month 24 or Last Visit Measure by Z-score [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    Bone mineral density (BMD) at lumbar spine (L2-L4) measured by Z-score. If Z-score is -2 or lower, it may suggest that something other than aging is causing abnormal bone loss.

  • Percent Change in Bone Mineral Density for L2-L4 From Baseline to Month 24 or Last Visit [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    Bone mineral density (BMD) at lumbar spine (L2-L4) measured by using Lunar or Hologic dual-energy X-ray absorptiometry (DXA) Instruments. Measurements were done in the lumbar vertebrae (L2-L4)


Secondary Outcome Measures:
  • Percentage Change in Bone Mineral Density for Femoral Neck (Right and Left Side) From Baseline to Month 24 [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    Bone mineral density (BMD) for femoral neck (right and left side) is measured by using Lunar or Hologic dual-energy X-ray absorptiometry (DXA) Instruments. Measurements were done on femoral neck (right and left side)

  • Percentage Change in Bone Mineral Density for Total Femoral Neck (Right and Left Side) From Baseline to Month 24 [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    Bone mineral density (BMD) for total femoral neck (right and left side) is measured by using Lunar or Hologic dual-energy X-ray absorptiometry (DXA) Instruments. Measurements were done on femoral neck (right and left side)

  • Change in Bone Mineral Density Os Calcis (Right and Left Side) From Baseline to Month 24 as Measured by Speed of Sound (SOS) [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    Bone mineral density (BMD) for Os calcis (right and left side) is measured by SOS; SOS is a Quantitative ultrasonography scanning and measures bone mass and strength and assesses bone microarchitecture by detecting the transmission of high-frequency sound waves through bone.

  • Change in Bone Mineral Density Os Calcis (Right and Left Side) From Baseline to Month 24 as Measured by Broadband Ultrasound Attenuation (BUA) [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    Bone mineral density (BMD) for Os calcis (right and left side) is measured by BUA; BUA is a Quantitative ultrasonography scanning and measures bone mass and strength and assesses bone microarchitecture by detecting the transmission of high-frequency sound waves through bone.

  • Change in Bone Mineral Density Phalanges II, III, IV, and V From Baseline to Month 24 or Last Visit as Measured by Amplitude-dependent Speed of Sound (ADSOS) [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    Bone mineral density (BMD) for Phalanges II, III, IV, and V is measured by ADSOS; ADSOS is a Quantitative ultrasonography scanning and measures bone mass and strength and assesses bone microarchitecture by detecting the transmission of high-frequency sound waves through bone.

  • Change in Serum CTX-carboxy-terminal Collagen Crosslinks From Baseline to Month 24 [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    CTX is a telopeptide that can be used as a biomarker in the serum to measure the rate of bone turnover. The test used to detect the CTX marker is specific to bone resorption.

  • Change in Aminoterminal Propeptide on Type I Procollagen (P1NP) From Baseline to Month 24 [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    Change in Aminoterminal propeptide on type I procollagen (P1NP) from baseline to month 24. P1NP is a marker for bone formation. It is a specific indicator of type 1 collagen deposition. P1NP is increased in states of high bone turnover

  • Change in Estradiol (E2) From Baseline to Month 24 [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    Change in Estradiol from baseline to month 24

  • Change in Follicle- Stimulating Hormone (FSH) From Baseline to Month 24 [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    Change in Follicle- Stimulating Hormone (FSH) from baseline to month 24

  • Change in Testosterone From Baseline to Month 24 [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    Change in Testosterone from baseline to month 24

  • Change in Sex Hormone Binding Globulin (SHGB) From Baseline to Month 24 [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    Change in Sex Hormone binding globulin (SHGB) from baseline to month 24

  • Change in Parathyroid Hormone (PTH) From Baseline to Month 24 [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    Change in Parathyroid Hormone (PTH) from baseline to month 24

  • Change in Vitamine D From Baseline to Month 24 [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    Change in Vitamine D from baseline to month 24

  • Change in Anti-Mueller Hormone (AMH) From Baseline to Month 24 [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    Change in anti-Mueller hormone (AMH) from baseline to month 24

  • Change in Inhibin A and Inhibin B From Baseline to Month 24 [ Time Frame: baseline, month 24 ] [ Designated as safety issue: No ]
    Change in Inhibin A and Inhibin B from baseline to month 24


Enrollment: 70
Study Start Date: October 2005
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zometa
Zoledronic acid 4mg as a 15-minute infusion every 3 months for a treatment period of 24 months (total of 8 infusions).
Drug: Zoledronic acid
Other Name: ZOL446, zoledronic acid, Zometa
Placebo Comparator: Placebo
Placebo as a 15-minute infusion every 3 months for a treatment period of 24 months (total of 8 infusions).
Drug: Placebo
Placebo

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female patients with histologically confirmed incident invasive breast cancer (T1-4) with positive hormone receptor status (ER and/or PgR positive) and no evidence of regional lymph node metastasis (N0) or distant metastasis (M0)
  • Patient has undergone complete primary tumor resection and axillary lymph node dissection less than 90 days before start of study drug treatment.
  • Patient is premenopausal at diagnosis of breast cancer (spontaneous and regular menses with premenopausal estradiol levels (>10 ng/dL)
  • Patient receives adjuvant standard chemoendocrine or endocrine therapy
  • Bone density at study entry > -2.5 T-Score

Exclusion Criteria:

  • History of treatment or disease affecting bone metabolism (e.g., Paget's disease, primary hyperparathyroidism), prior treatment with bisphosphonates or treatments for osteoporosis in addition to calcium and vitamin D
  • Abnormal renal function
  • Current active dental problems including infection of 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)
  • Pregnancy or lactation
  • Women of childbearing potential not applying a medically recognized form of contraception (i.e., oral contraceptives or implants, IUD, vaginal diaphragm or sponge, or condom with spermicide)

Other protocol-defined inclusion/exclusion criteria may apply

  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: NCT00375505

Locations
Germany
Novartis Investigative Site
Marburg, Germany, 35043
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmeceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00375505     History of Changes
Other Study ID Numbers: CZOL446GDE21 
Study First Received: September 11, 2006
Results First Received: May 18, 2015
Last Updated: August 11, 2015
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
Breast Cancer
Premenopausal
Bone mineral density
Cancer therapy induced bone loss
zoledronic acid

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 23, 2016