An Open-Label, Non-Randomized, Single center Study to Evaluate the Use of Zoledronic Acid in the Prevention of Cancer Treatment-Related Bone Loss in Postmenopausal Women with ER+ and/or PgR+ Breast Cancer Receiving Letrozole as Adjuvant Therapy

• Conditions: Prevention of cancer treatment-related bone loss in postmenopausal women with resected stage I-IIIa hormone receptor positive breast cancer, who will receive letrozole as adjuvant therapy.

• Registration Number: EUCTR2004-004796-11-DE
• Lead Sponsor: Klinikum Augsburg

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-01-29
• Last Update Posted: 29 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 100

Inclusion Criteria

Patients must fulfill all of these inclusion criteria:
1. Signed written informed consent.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 – 2
3. Postmenopausal status defined by one of the following:
• Age >/= 55 years with cessation of menses.
• Age <55 but no spontaneous menses for at least 1 year.
• Age <55 and spontaneous menses within the past 1 year, but currently amenorrheic (e.g., spontaneous, or secondary to hysterectomy), and with postmenopausal gonadotrophin levels (luteinizing hormone and follicle stimulating hormone levels >40 IU/L) or postmenopausal estradiol levels (<5ng/dL) or according to the definition of postmenopausal range” for the laboratory involved.
• Bilateral oophorectomy.
4. Hormone receptor positive defined as ER and/or PgR >/= 2 (Remmele/Stegner)
5. Patients with a baseline lumbar spine BMD T-score at or above - 2.0 SD.
6. Adequately diagnosed and treated invasive breast cancer defined as:
• Patients with invasive breast cancer whose tumor can be removed by an appropriate surgical procedure such as mastectomy or breast conserving surgery and who receive, if appropriate, additional local (e.g. radiotherapy) and/or systemic (i.e. adjuvant chemotherapy) treatments, according to best practice.
• Patients may have also received prior neoadjuvant chemotherapy. Prior neoadjuvant chemotherapy must be completed before entering the patient onto the present protocol.
• The date of registration must be no more than:
a. 4 weeks from completion of surgery (in case of surgery alone), or
b. 4 weeks from completion of surgery (in case of surgery + radiotherapy) or
c. 4 weeks after completion of adjuvant chemotherapy (if planned to be given before the endocrine therapy) or
d. 4 weeks after completion of chemotherapy followed by radiation.
Completion of chemotherapy is defined as completion of the last full course including recovery time.
• When the plan is to give concomitant adjuvant chemotherapy and hormonotherapy, the treatment should start at the same time and the date of registration must be no more than 4 weeks from completion of surgery;
• Patients must have no clinical or radiological evidence of distant metastasis, and no other concomitant malignancy.
7. Patients must be able to swallow the study medication and have adequate unassisted oral intake to maintain a reasonable state of nutrition.
8. Life expectancy of at least 12 months from registration.

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

1. Patients with any clinical or radiological evidence of distant spread of their disease at any point before registration.
2. Patients with invasive bilateral breast cancer.
3. Patients with any clinical or radiological evidence of existing fracture in the lumbar spine and/or total hip.
4. Patients with a history of fracture with low-density or no associated trauma.
5. Patients who have started adjuvant hormonal therapy or who have completed adjuvant hormonal therapy prior to registration.
6. Patients who have received any endocrine therapy within the past 12 months (other than neoadjuvant tamoxifen or torimefene, insulin and/or anti-diabetic medications, and thyroid hormone replacement). Hormone replacement therapy must be discontinued at least 4 weeks prior to registration.
7. Patients currently receiving oral bisphosphonates. Oral bisphosphonates must be discontinued within 3 weeks of baseline evaluations.
8. Patients who have received prior treatment with systemic corticosteroids within the past 12 months (short term corticosteroid therapy, e.g. to prevent/treat chemotherapy-induced nausea/vomiting is allowed).
9. Patients with prior exposure to anabolic steroids or growth hormone within the past 6 months.
10. Treatment with tibolone must be discontinued at least 4 weeks prior to registration.
11. Any prior use of parathyroid hormone (PTH) for more than 1 week.
12. Prior use of systemic sodium fluoride for > 3 months during the past 2 years.
13. Patients currently treated with any drugs known to affect the skeleton (e.g., calcitonin, mithramycin, or gallium nitrate) within 2 weeks prior to registration.
14. Patients with previous or concomitant malignancy (not breast cancer) within the past 5 years EXCEPT adequately 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.
15. Patients with other non-malignant systemic diseases including uncontrolled infections, uncontrolled type 2 diabetes mellitus, uncontrolled thyroid dysfunction, cardiovascular, renal, hepatic, and lung diseases which would prevent prolonged follow-up. Patients with previous history of thrombosis or thromboembolism can be included only if suitable for prolonged follow-up and not on steroids. Patients with a known history of HIV are excluded.
16. 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}
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[72 x serum creatinine (mg/dL)]
17. 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.
18. Recent (within 6 weeks) or planned dental or jaw surgery (e.g.. extraction, implants).
19. History of diseases with influence on bone metabolism, such as Paget’s disease, Osteo-genesis Imperfecta, and primary or secondary hyperthyroidism within the 12 months prior to study entry.
20. Patients with baseline lumbar spine BMD T-score below –2.0 SD.
21. Known hypersensitivity to zoledronic acid or other bisphosphonates.
22. Mental illness that precludes the patient from giving informed consent.
23. WBC </

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified