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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00375505

Enrollment

Registered

2006-09-13

Start date

2005-10-31

Completion date

2014-05-31

Last updated

2015-09-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer

Keywords

Breast Cancer, Premenopausal, Bone mineral density, Cancer therapy induced bone loss, zoledronic acid

Brief summary

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

Interventions

DRUGZoledronic acid

DRUGPlacebo

Placebo

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

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/

Design outcomes

Primary

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

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

Countries

Germany

Participant flow

Participants by arm

Arm	Count
Placebo Placebo as a 15-minute infusion every 3 months for a treatment period of 24 months (total of 8 infusions).	36
Zometa Zoledronic Acid 4mg as a 15-minute infusion every 3 months for a treatment period of 24 months (total of 8 infusions).	34
Total	70

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	2

Baseline characteristics

Characteristic	Placebo	Zometa	Total
Age, Continuous	42.8 years STANDARD_DEVIATION 6.3	43.2 years STANDARD_DEVIATION 6	43.0 years STANDARD_DEVIATION 6.1
Sex: Female, Male Female	36 Participants	34 Participants	70 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	36 / 36	33 / 34
serious Total, serious adverse events	3 / 36	6 / 34

Outcome results

Primary

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.

Time frame: baseline, month 24