- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00375752
Efficacy and Safety of Letrozole vs. Letrozole Plus Zoledronic Acid as Endocrine Therapy Before Surgery in Postmenopausal Patients With Breast Cancer (FEMZONE)
June 6, 2017 updated by: Novartis Pharmaceuticals
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)
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
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Detailed Description
Open-label, multicenter, randomized phase II trial over approx 6.5 months of neoadjuvant treatment with letrozole with or without zoledronic acid in postmenopausal patients with primary breast cancer.
A total of approximately 850 patients were originally planned to be enrolled; primary study endpoint was the objective response rate (according to modified RECIST criteria) after 6 months of treatment.
After the core study, patients willing to participate were followed-up for further 5 years.
Study Type
Interventional
Enrollment (Actual)
168
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Amberg, Germany, 92224
- Novartis Investigative Site
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Berlin, Germany, 10365
- Novartis Investigative Site
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Boeblingen, Germany, 71032
- Novartis Investigative Site
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Celle, Germany, 29223
- Novartis Investigative Site
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Ebersberg, Germany, 85560
- Novartis Investigative Site
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Erlangen, Germany, 91052
- Novartis Investigative Site
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Essen, Germany, 45147
- Novartis Investigative Site
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Essen, Germany, 45276
- Novartis Investigative Site
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Esslingen, Germany, 73730
- Novartis Investigative Site
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Freiburg, Germany, 79106
- Novartis Investigative Site
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Fürth, Germany, 90766
- Novartis Investigative Site
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Halle, Germany, 06110
- Novartis Investigative Site
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Hamburg, Germany, 22457
- Novartis Investigative Site
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Hameln, Germany, 31785
- Novartis Investigative Site
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Hanau, Germany, 63450
- Novartis Investigative Site
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Hannover, Germany, 30625
- Novartis Investigative Site
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Heilbronn, Germany, 74064
- Novartis Investigative Site
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Kempten, Germany, 87439
- Novartis Investigative Site
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Koeln, Germany, 50924
- Novartis Investigative Site
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Leipzig, Germany, 04277
- Novartis Investigative Site
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Muenchen, Germany, 81377
- Novartis Investigative Site
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Muenchen, Germany, 81675
- Novartis Investigative Site
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Muenchen, Germany, 81545
- Novartis Investigative Site
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Neunkirchen, Germany, 66538
- Novartis Investigative Site
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Rheinfelden/Baden, Germany, 79618
- Novartis Investigative Site
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Ulm, Germany, 89070
- Novartis Investigative Site
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Ulm, Germany, 89703
- Novartis Investigative Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Letrozole
Letrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment
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2.5 mg.tablet.
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Experimental: Zolendronic Acid + Letrozole
2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvant treatment plus zoledronic acid 4 mg i.v.
q4w
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2.5 mg.tablet.
4 mg or an adjusted dose based on renal function in 100 ml physiologic (o.9%) normal saline, (as an intravenous infusion over no less than 15 minutes)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Sum of longest diameter for all target lesions was reported as baseline sum LD.
Baseline sum LD was used as reference to characterize objective tumor response.
Response Evaluation Criteria in Solid Tumors has 4 response categories.
CR (complete response) = disappearance of all target lesions, PR (partial response)= 30% decrease in sum of longest diameter of target lesions, PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions and SD(stable disease)=small changes that do not meet criteria.
Analysis was underpowered due to insufficient recruitment rate.
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6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Best RECIST Response Based on Central Review at 6 Mos
Time Frame: 6 Months
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Best response is defined as the best response the patients has reached during the 6 months of treatment.
Response Evaluation Criteria in Solid Tumors (RECIST) has 4 response categories.
CR (complete response) = disappearance of all target lesions, PR (partial response) = 30% decrease in the sum of the longest diameter of target lesions, PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions and SD (stable disease) = small changes that do not meet criteria.
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6 Months
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Number of Patients With Breast Conserving Surgery at 6 Months
Time Frame: Every 6 months
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Every 6 months
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Change From Baseline in Tumor Size (Longest Diameter) at Month 6
Time Frame: Baseline, Month 6
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Tumor size (sum of longest diameter)was analyzed based on the diameters values provided with the central review.
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Baseline, Month 6
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Mean Changes From Baseline in FACT-B Total Score at 6 Months (ITT, Data as Observed)
Time Frame: baseline and 6 mos
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The FACT-B total score is calculated by summing all five unweighted subscale scores, with total scores in the range of 0-144.To Derive a FACT-B total score: all sections added together The higher the score the better the QoL
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baseline and 6 mos
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 1, 2006
Primary Completion (Actual)
December 16, 2010
Study Completion (Actual)
December 16, 2010
Study Registration Dates
First Submitted
September 11, 2006
First Submitted That Met QC Criteria
September 11, 2006
First Posted (Estimate)
September 13, 2006
Study Record Updates
Last Update Posted (Actual)
June 26, 2017
Last Update Submitted That Met QC Criteria
June 6, 2017
Last Verified
June 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Hormone Antagonists
- Aromatase Inhibitors
- Steroid Synthesis Inhibitors
- Estrogen Antagonists
- Letrozole
Other Study ID Numbers
- CZOL446GDE19
- 2004-004007-37 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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