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

Study Overview
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Brief Summary
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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

Official Title
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Zoledronic Acid in the Prevention of Cancer Therapy Induced Bone Loss

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Zoledronic acid
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zometa<br>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<br> <br> * Other names: ZOL446, zoledronic acid, Zometa;|
| Placebo Comparator: Placebo<br>Placebo as a 15-minute infusion every 3 months for a treatment period of 24 months (total of 8 infusions). | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Premenopausal, Bone mineral density, Cancer therapy induced bone loss, zoledronic acid