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

NCT00375505 | Completed Phase 3 Results

• 1 other identifier: CZOL446GDE21
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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

Conditions

Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (15)

• Percentage Change in Bone Mineral Density for Femoral Neck (Right and Left Side) From Baseline to Month 24

  baseline, month 24

• Percentage Change in Bone Mineral Density for Total Femoral Neck (Right and Left Side) From Baseline to Month 24

  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)

  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)

  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)

  baseline, month 24

Study Arms (2)

Zometa

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Placebo as a 15-minute infusion every 3 months for a treatment period of 24 months (total of 8 infusions).

Drug: Placebo

Interventions

Zoledronic acid DRUG

Also known as: ZOL446, zoledronic acid, Zometa

Zometa

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Marburg, 35043, Germany

Location

Related Publications (1)

• Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.

  PMID: 38979716 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Zoledronic Acid

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

• Novartis Pharmaceuticals

  Novartis Pharmeceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2006
• First Posted: September 13, 2006
• Study Start: October 1, 2005
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: September 7, 2015
• Results First Posted: September 7, 2015

Record last verified: 2015-08

Locations

DE (1)