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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00375752
First received: September 11, 2006
Last updated: August 5, 2015
Last verified: August 2015
  Purpose

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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
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:

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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Every 6 months ] [ Designated as safety issue: No ]
  • Change From Baseline in Tumor Size (Longest Diameter) at Month 6 [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    Tumor size (sum of longest diameter)was analyzed based on the diameters values provided with the central review.


Enrollment: 168
Study Start Date: June 2006
Estimated Study Completion Date: December 2015
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Letrozole
Letrozole 2.5 mg (one tablet) once daily oral administration for the duration of 6.5 months.
Drug: Letrozole
2.5 mg.tablet.
Experimental: Zolendronic Acid + Letrozole

Zoledronic Acid 4 mg or an adjusted dose based on renal function in 100 ml physiologic (0.9%) normal saline, (as an intravenous infusion over no less than 15 minutes), every 4 weeks for the duration of 6.0 months.

Letrozole 2.5 mg. (one tablet)once daily oral administration for the duration of 6.5 months.

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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00375752

Locations
Germany
Novartis Investigative Site
Amberg, Germany, 92224
Novartis Investigative Site
Berlin, Germany, 10365
Novartis Investigative Site
Böblingen, 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, 45276
Novartis Investigative Site
Essen, Germany, 45147
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, 81545
Novartis Investigative Site
Muenchen, Germany, 81675
Novartis Investigative Site
Muenchen, Germany, 81377
Novartis Investigative Site
Neunkirchen, Germany, 66538
Novartis Investigative Site
Rheinfelden/Baden, Germany, 79618
Novartis Investigative Site
Ulm, Germany, 89703
Novartis Investigative Site
Ulm, Germany, 89070
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmeceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00375752     History of Changes
Other Study ID Numbers: CZOL446GDE19, 2004-004007-37
Study First Received: September 11, 2006
Results First Received: March 30, 2012
Last Updated: August 5, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

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

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Diphosphonates
Letrozole
Zoledronic acid
Antineoplastic Agents
Aromatase Inhibitors
Bone Density Conservation Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015