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

Zoledronic Acid in the Prevention of Cancer Therapy Induced Bone Loss

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

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Placebo; Drug: Zoledronic acid

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Marburg, Germany, 35043
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Bone Mineral Density (BMD) Measured by Dual (Energy) X-ray Absorptiometry (DXA) at Lumbar Spine (L2-L4) From Baseline to Month 24	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.	baseline, month 24
Change in Bone Mineral Density (BMD) at Lumbar Spine (L2-L4) From Baseline to Month 24 or Last Visit Measure by T-score	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.	baseline, month 24
Change in Bone Mineral Density (BMD) at Lumbar Spine (L2-L4) From Baseline to Month 24 or Last Visit Measure by Z-score	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.	baseline, month 24
Percent Change in Bone Mineral Density for L2-L4 From Baseline to Month 24 or Last Visit	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)	baseline, month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in Bone Mineral Density for Femoral Neck (Right and Left Side) From Baseline to Month 24	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)	baseline, month 24
Percentage Change in Bone Mineral Density for Total Femoral Neck (Right and Left Side) From Baseline to Month 24	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)	baseline, month 24
Change in Bone Mineral Density Os Calcis (Right and Left Side) From Baseline to Month 24 as Measured by Speed of Sound (SOS)	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.	baseline, month 24
Change in Bone Mineral Density Os Calcis (Right and Left Side) From Baseline to Month 24 as Measured by Broadband Ultrasound Attenuation (BUA)	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.	baseline, month 24
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)	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.	baseline, month 24
Change in Serum CTX-carboxy-terminal Collagen Crosslinks From Baseline to Month 24	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.	baseline, month 24
Change in Aminoterminal Propeptide on Type I Procollagen (P1NP) From Baseline to Month 24	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	baseline, month 24
Change in Estradiol (E2) From Baseline to Month 24	Change in Estradiol from baseline to month 24	baseline, month 24
Change in Follicle- Stimulating Hormone (FSH) From Baseline to Month 24	Change in Follicle- Stimulating Hormone (FSH) from baseline to month 24	baseline, month 24
Change in Testosterone From Baseline to Month 24	Change in Testosterone from baseline to month 24	baseline, month 24
Change in Sex Hormone Binding Globulin (SHGB) From Baseline to Month 24	Change in Sex Hormone binding globulin (SHGB) from baseline to month 24	baseline, month 24
Change in Parathyroid Hormone (PTH) From Baseline to Month 24	Change in Parathyroid Hormone (PTH) from baseline to month 24	baseline, month 24
Change in Vitamine D From Baseline to Month 24	Change in Vitamine D from baseline to month 24	baseline, month 24
Change in Anti-Mueller Hormone (AMH) From Baseline to Month 24	Change in anti-Mueller hormone (AMH) from baseline to month 24	baseline, month 24
Change in Inhibin A and Inhibin B From Baseline to Month 24	Change in Inhibin A and Inhibin B from baseline to month 24	baseline, month 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: September 11, 2006
• First Submitted That Met QC Criteria: September 11, 2006
• First Posted (Estimate): September 13, 2006

Study Record Updates

• Last Update Posted (Estimate): September 7, 2015
• Last Update Submitted That Met QC Criteria: August 11, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Breast Cancer; Premenopausal; Bone mineral density; zoledronic acid; Cancer therapy induced bone loss
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid
• Other Study ID Numbers: CZOL446GDE21