Influence of Zoledronic acid (Zometa®) on bone mineral density and bone ultrasonometry in premenopausal women with hormone receptor positive breast cancer and neoadjuvant or adjuvant chemoendocrine or endocrine treatment - ProBONE II

• Register: EUCTR
• Last refreshed on: 5 August 2014
• Main ID: EUCTR2004-002832-24-DE
• Date of registration: 29/11/2005
• Prospective Registration: No
• Primary sponsor: Novartis Pharma GmbH
• Public title: Influence of Zoledronic acid (Zometa®) on bone mineral density and bone ultrasonometry in premenopausal women with hormone receptor positive breast cancer and neoadjuvant or adjuvant chemoendocrine or endocrine treatment - ProBONE II
• Scientific title: Influence of Zoledronic acid (Zometa®) on bone mineral density and bone ultrasonometry in premenopausal women with hormone receptor positive breast cancer and neoadjuvant or adjuvant chemoendocrine or endocrine treatment - ProBONE II
• Date of first enrolment: 27/07/2005
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-002832-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
• Female patients with histologically confirmed incident invasive breast cancer (T1-4).
• No evidence of distant metastasis (M0)
• Patients under adjuvant chemoendocrine or endocrine therapy: Node negative (pN-) and Node positive (pN+; <= 4 positive lymph nodes) patients
• Patients under neoadjuvant chemotherapy: no clinical evidence for nodal involvement
• Hormone receptor status (ER and/or PgR) is positive (defined as >=10% receptor positive cells or >=10fmol receptor protein/mg cytosol protein or IRS >2)
• Age >= 18 years
• Patient is premenopausal: determined by spontaneous and regular menses at diagnosis of breast cancer or by premenopausal estradiol levels (>20ng/L) at diagnosis of breast cancer
• Patient receives neoadjuvant chemotherapy or adjuvant standard chemoendocrine or endocrine therapy
• 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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
•Previous or concomitant malignancy (not breast cancer) within the past 5 years except adequaetely treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients who have had a previous other malignancy must have been disease-free for five years
•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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Hormonreceptor positive breast cancer in premenopausal women

Intervention(s)

Product Name: Zometa 4mg/5ml
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Zoledronic acid
Current Sponsor code: CGP42446
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-

Primary Outcome(s)

Main Objective: 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 positive breast cancer and neoadjuvant or adjuvant chemoendocrine or endocrine treatment compared to placebo.

Primary end point(s): Change in bone mineral density (BMD) measured by DXA at lumbar spine (L2-L4) between baseline and 24 months.

Secondary Objective: 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)

Secondary ID(s)

CZOL446GDE21