E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary, hormonreceptor negative breast cancer in premenopausal women |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This study is designed to demonstrate superiority of Zometa® (Zoledronic acid) 4 mg or adjusted dose based on renal function, 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 compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of the trial are to explore the influence of the therapy with Zometa® compared to placebo with regard to: • Bone mineral density (BMD) measured by DXA at dual hips and os calcis after 24 months • Bone mineral density (BMD) by QUS at os calcis and phalanges at 24 months • Course of biochemical markers of bone turn over (FSH, estradiol (E2), osteocalcin, PINP, procollagene-I-peptid, deoxypyridinoline in serum) • Pathologic Fractures (proportion of patients with at least one fracture, type of fracture(s), number of fractures per patient, time to first pathologic fracture) during 24 months • Development of metastases as assessed by X-ray, CT, bone scan or MRI (proportion of patients developing metastases, number and localization, metastases-free survival) during 24 months and during 60 months • Safety and tolerability (adverse events / serious adverse events; standard safety laboratory)
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
• Female patients with histologically confirmed incident invasive breast cancer (T1-4). • No evidence of distant metastasis (M0) • Node negative (N0) and node positive (N1-4) patients • Patient has undergone complete primary tumor resection and axillary lymph node dissection less than 90 days before start of study drug treatment. • Hormone receptor status negative • Age >= 18 years • Patient is premenopausal at diagnosis of breast cancer (spontaneous and regular menses with premenopausal estradiol levels (>10 ng/mL) • 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 • Patient has given written informed consent prior to any study-specific procedure • Patient should be available for Follow-up
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E.4 | Principal exclusion criteria |
• History of treatment or disease affecting bone metabolism (e.g., Paget’s disease, primary hyperparathyroidism) • Known visceral metastasis or bone metastases • Prior treatment with bisphosphonates • Estrogens or treatments for osteoporosis in addition to calcium and vitamin D • Severe physical or psychological concomitant diseases that might impair compliance with the provisions of the study protocol or that might impair the assessment of drug or patient safety, e.g. clinically significant ascites, cardiac failure, NYHA III or IV, clinically relevant pathologic findings in ECG • 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 as evidenced by a calculated creatinine clearance < 30 ml/minute. Creatinine clearance (CrCl) is calculated using the Cockcroft-Gault formula: CrCl= [140-age (years)] x weight (kg) {x 0.85 for female patients} [72 x serum creatinine (mg/dL)] • 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) • Use of other investigational drugs (drugs not marketed for any indication) within 6 months before start of study and participation in other clinical study. • 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) • Known history or present abuse of alcohol or drugs (accepted social alcohol usage will not exclude the patient) • History of noncompliance to medical regimens and patients who are considered potentially unreliable or incapable of giving informed consent as judged by the investigator
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in bone mineral density (BMD) measured by DXA at lumbar spine between baseline and 24 months. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |