This trial is active, not recruiting.

Condition breast neoplasms
Treatments letrozole, zoledronic acid
Phase phase 2/phase 3
Sponsor Novartis
Start date May 2006
End date December 2010
Trial size 168 participants
Trial identifier NCT00375752, CZOL446GDE19


This study will evaluate the safety/efficacy of zoledronic acid when given by intravenous infusion every 4 weeks in addition to letrozole as endocrine therapy in postmenopausal patients with hormone responsive breast cancer

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
(Active Comparator)
Letrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment.
letrozole Femara®)
Letrozole was provided as 2.5 mg tablets for oral administration. Treatment was scheduled as 2.5 mg once daily for approximately 6.5 months.
2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvant treatment plus zoledronic acid 4 mg i.v. q4w
letrozole Femara®)
Letrozole was provided as 2.5 mg tablets for oral administration. Treatment was scheduled as 2.5 mg once daily for approximately 6.5 months.
zoledronic acid Zometa®
Zoledronic acid was provided as solution concentrate for intravenous infusion. 5 mL concentrate contained 4 mg zoledronic acid and was to be diluted for infusion in 100 mL normal saline. Treatment was scheduled as 4 mg i.v. at intervals of 4 weeks for a duration of 6 months. The duration of each infusion should not be shorter than 15 minutes.

Primary Outcomes

Tumor Response Rate (Complete Response (CR) or Partial Response (PR)) Based on MRI- or Mammography and/or Sonography According to Modified RECIST Criteria at Month 6
time frame: 6 months

Secondary Outcomes

Best RECIST Response Based on Central Review
time frame: 6 Months
Number of Patients With Breast-conserving Surgery
time frame: Every 6 months
Change From Baseline in Tumor Size (Longest Diameter) at Month 6
time frame: Baseline, Month 6
To Compare Pathologic Complete Response (pCR)
time frame: Every 6 months
To Compare BC Deaths and Overall Survival
time frame: Every 6 months
To Compare the Quality of Life Using the FACT-B Questionnaire
time frame: Every 6 months

Eligibility Criteria

Female participants of any age.

Inclusion criteria: - Postmenopausal women with primary invasive breast cancer, histologically confirmed by core needle biopsy, whose tumors are estrogen (ER) and / or progesterone (PgR) positive - Clinical Stage T1c (Size ≥ 1.5 cm), T2, T3, T4a, b, c, N0 or N1, M0 (TNM Classification). According to the modified RECIST criteria, tumors of size ≥ 1.5 cm are considered measurable by mammography and can be determined as target lesions). - Tumor measurable by mammography, sonography and clinical examination. - Adequate bone marrow, renal and hepatic function - Good health status (ECOG Performance status of 0, 1 or 2) Exclusion criteria: - Prior treatment with letrozole or bisphosphonates. Prior and concomitant anti-breast-cancer treatments such as chemotherapy, immunotherapy / biological response modifiers (BRM's), endocrine therapy other than letrozole (including steroids), and radiotherapy. Patients who have received hormone replacement therapy (HRT) will NOT be excluded, provided that HRT is discontinued at least 2 weeks prior to entry into the study. - Patients with unstable angina, or uncontrolled cardiac disease (e.g. Class III and IV New York Heart Association's Functional Classification, see Appendix 9) or uncontrolled endocrine disorders. - Evidence of inflammatory breast cancer or distant metastasis. - 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). - History of diseases with influence on bone metabolism, such as Paget's disease, Osteogenesis Imperfecta, and primary or secondary hyperthyroidism within the 12 months prior to study entry Other protocol-defined inclusion/exclusion criteria may apply

Additional Information

Official title Neoadjuvant Therapy for Postmenopausal Women With ER and/or PgR Positive Breast Cancer. A Randomized Open Phase II Trial Evaluating the Efficacy of a 6 Months Preoperative Treatment With Letrozole (2.5 mg/Day) With or Without Zoledronic Acid (4 mg Every 4 Weeks)
Trial information was received from ClinicalTrials.gov and was last updated in April 2014.
Information provided to ClinicalTrials.gov by Novartis.