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Efficacy and Safety of Letrozole vs. Letrozole Plus Zoledronic Acid as Endocrine Therapy Before Surgery in Postmenopausal Patients With Breast Cancer (FEMZONE)

This study has been terminated.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals ) Identifier:
First received: September 11, 2006
Last updated: June 6, 2017
Last verified: June 2017
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

Condition Intervention Phase
Breast Neoplasms Drug: Letrozole Drug: Zolendronic Acid Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Open-label, multicenter, randomized
Primary Purpose: Treatment
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)

Resource links provided by NLM:

Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • 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.

Secondary Outcome Measures:
  • Best RECIST Response Based on Central Review at 6 Mos [ Time Frame: 6 Months ]
    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.

  • Number of Patients With Breast Conserving Surgery at 6 Months [ Time Frame: Every 6 months ]
  • Change From Baseline in Tumor Size (Longest Diameter) at Month 6 [ Time Frame: Baseline, Month 6 ]
    Tumor size (sum of longest diameter)was analyzed based on the diameters values provided with the central review.

  • Mean Changes From Baseline in FACT-B Total Score at 6 Months (ITT, Data as Observed) [ Time Frame: baseline and 6 mos ]

    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

    • + __________ + __________ + __________ + __________ =________=FACT-B Total score (PWB score) (SWB score) (EWB score) (FWB score) (BCS score)

Enrollment: 168
Actual Study Start Date: June 1, 2006
Study Completion Date: December 16, 2010
Primary Completion Date: December 16, 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Letrozole
Letrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment
Drug: Letrozole
2.5 mg.tablet.
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
Drug: Letrozole
2.5 mg.tablet.
Drug: Zolendronic Acid
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)

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.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

  Contacts and Locations
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Please refer to this study by its identifier: NCT00375752

Novartis Investigative Site
Amberg, Germany, 92224
Novartis Investigative Site
Berlin, Germany, 10365
Novartis Investigative Site
Boeblingen, Germany, 71032
Novartis Investigative Site
Celle, Germany, 29223
Novartis Investigative Site
Ebersberg, Germany, 85560
Novartis Investigative Site
Erlangen, Germany, 91052
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Essen, Germany, 45276
Novartis Investigative Site
Esslingen, Germany, 73730
Novartis Investigative Site
Freiburg, Germany, 79106
Novartis Investigative Site
Fürth, Germany, 90766
Novartis Investigative Site
Halle, Germany, 06110
Novartis Investigative Site
Hamburg, Germany, 22457
Novartis Investigative Site
Hameln, Germany, 31785
Novartis Investigative Site
Hanau, Germany, 63450
Novartis Investigative Site
Hannover, Germany, 30625
Novartis Investigative Site
Heilbronn, Germany, 74064
Novartis Investigative Site
Kempten, Germany, 87439
Novartis Investigative Site
Koeln, Germany, 50924
Novartis Investigative Site
Leipzig, Germany, 04277
Novartis Investigative Site
Muenchen, Germany, 81377
Novartis Investigative Site
Muenchen, Germany, 81545
Novartis Investigative Site
Muenchen, Germany, 81675
Novartis Investigative Site
Neunkirchen, Germany, 66538
Novartis Investigative Site
Rheinfelden/Baden, Germany, 79618
Novartis Investigative Site
Ulm, Germany, 89070
Novartis Investigative Site
Ulm, Germany, 89703
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmeceuticals
  More Information

Additional Information:
Responsible Party: Novartis Pharmaceuticals Identifier: NCT00375752     History of Changes
Other Study ID Numbers: CZOL446GDE19
2004-004007-37 ( EudraCT Number )
Study First Received: September 11, 2006
Results First Received: March 30, 2012
Last Updated: June 6, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Breast cancer
Anti tumor potential
Zoledronic acid
Neoadjuvant treatment
Hormone responsive breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Zoledronic acid
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Bone Density Conservation Agents processed this record on September 21, 2017