A Study of Zoledronic Acid in the Prevention of Cancer Therapy-induced Bone Loss

NCT00333229 | Terminated Phase 4 Results

• 2 other identifiers: CZOL446GDE132004-002831-14
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Breast cancer and osteoporosis are two of the most frequent diseases in women. Estrogen may be associated with bone loss and the risk of breast cancer because of its potent effects on the mitotic activity of breast epithelium and on bone turnover. This study is will assess the safety and efficacy of Zoledronic acid 4 mg, given every 3 months over 24 months, in improving bone mineral density in premenopausal women with hormone receptor negative breast cancer and adjuvant chemotherapeutic treatment compared to placebo. This study is not recruiting patients in the United States.

Conditions

Primary Hormone Receptor Negative Breast Cancer in Premenopausal Women

Keywords

Breast Cancer; premenopausal; Bone Mineral density; Cancer therapy induced bone loss; zoledronic acid

Outcome Measures

Primary Outcomes (1)

• Change in Bone Mineral Density (BMD) Measured by DXA at Lumbar Spine (L2-L4) Between Baseline and 24 Months.

  24 months

Secondary Outcomes (4)

• Bone Mineral Density (BMD) Measured by QUS at os Calcis and Phalanges After 24 Months

  2 years

• Course of Biochemical Markers of Bone Turn Over (FSH, Estradiol (E2), Osteocalcin, PINP, Procollagene-I-peptid, Deoxypyridinoline in Serum)

  2 years

• Pathologic Fractures During 24 Month

  2 years

• Development of Metastases as Assessed by X-ray, CT, or MRI During 24 Months and During 60 Months

  2 years

Study Arms (2)

Zoledronic Acid

EXPERIMENTAL

Patients randomized into the Zometa arm received a total of 8 study drug infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.

Drug: Zoledronic Acid

Placebo

PLACEBO COMPARATOR

Patients randomized into the Placebo Arm received a total of 8 placebo infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months.

Drug: Placebo

Interventions

Zoledronic Acid DRUG

4 mg zoledronic acid in 5 mL concentrate solution. Plastic vials.

Zoledronic Acid

Placebo DRUG

Matching 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 no evidence of regional lymph node metastasis (N0) or distant metastasis (M0) and after complete primary tumor resection and axillary lymph node dissection less than 90 days before start of study drug treatment.
• Hormone receptor status is negative
• Patient is premenopausal (spontaneous and regular menses with premenopausal estradiol levels (\>10ng/dL)
• Patient receives adjuvant standard chemotherapy with approved cytotoxic chemotherapeutic drugs (e.g. AC 4-6 cycles) (prior neoadjuvant CT is allowed)
• Bone density at study entry \> -2.5 T-Score

You may not qualify if:

• Prior treatment with bisphosphonates and estrogens or treatments for osteoporosis in addition to calcium and vitamin D
• Severe physical or psychological concomitant diseases and other known concurrent, severe medical disorder jeopardizing the life of the patient in the immediate future (e.g., myocardial infarction in previous six months, angina pectoris despite treatment, uncontrolled severe arterial hypertension, progressive cardiac or respiratory failure)
• Known hypersensitivity to bisphosphonates
• 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 and recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants)

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

Related Links

• Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.

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 Pharmaceuticals

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 4
• 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: May 31, 2006
• First Posted: June 2, 2006
• Study Start: March 1, 2006
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: November 25, 2014
• Results First Posted: November 25, 2014

Record last verified: 2014-11

Locations

DE (1)