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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)

Primary Purpose

Breast Neoplasms

Status
Terminated
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Letrozole
Zolendronic Acid
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Neoplasms focused on measuring Breast cancer, Anti tumor potential, Letrozole, Zoledronic acid, Neoadjuvant treatment, Hormone responsive breast cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Letrozole

Zolendronic Acid + Letrozole

Arm Description

Letrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment

2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvant treatment plus zoledronic acid 4 mg i.v. q4w

Outcomes

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
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
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
Change From Baseline in Tumor Size (Longest Diameter) at 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)
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)

Full Information

First Posted
September 11, 2006
Last Updated
June 6, 2017
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00375752
Brief Title
Efficacy and Safety of Letrozole vs. Letrozole Plus Zoledronic Acid as Endocrine Therapy Before Surgery in Postmenopausal Patients With Breast Cancer
Acronym
FEMZONE
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Terminated
Study Start Date
June 1, 2006 (Actual)
Primary Completion Date
December 16, 2010 (Actual)
Study Completion Date
December 16, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Neoplasms
Keywords
Breast cancer, Anti tumor potential, Letrozole, Zoledronic acid, Neoadjuvant treatment, Hormone responsive breast cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Open-label, multicenter, randomized
Allocation
Randomized
Enrollment
168 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Letrozole
Arm Type
Active Comparator
Arm Description
Letrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment
Arm Title
Zolendronic Acid + Letrozole
Arm Type
Experimental
Arm Description
2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvant treatment plus zoledronic acid 4 mg i.v. q4w
Intervention Type
Drug
Intervention Name(s)
Letrozole
Intervention Description
2.5 mg.tablet.
Intervention Type
Drug
Intervention Name(s)
Zolendronic Acid
Intervention Description
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)
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Best RECIST Response Based on Central Review at 6 Mos
Description
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.
Time Frame
6 Months
Title
Number of Patients With Breast Conserving Surgery at 6 Months
Time Frame
Every 6 months
Title
Change From Baseline in Tumor Size (Longest Diameter) at Month 6
Description
Tumor size (sum of longest diameter)was analyzed based on the diameters values provided with the central review.
Time Frame
Baseline, Month 6
Title
Mean Changes From Baseline in FACT-B Total Score at 6 Months (ITT, Data as Observed)
Description
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)
Time Frame
baseline and 6 mos

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmeceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Amberg
ZIP/Postal Code
92224
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
10365
Country
Germany
Facility Name
Novartis Investigative Site
City
Boeblingen
ZIP/Postal Code
71032
Country
Germany
Facility Name
Novartis Investigative Site
City
Celle
ZIP/Postal Code
29223
Country
Germany
Facility Name
Novartis Investigative Site
City
Ebersberg
ZIP/Postal Code
85560
Country
Germany
Facility Name
Novartis Investigative Site
City
Erlangen
ZIP/Postal Code
91052
Country
Germany
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45276
Country
Germany
Facility Name
Novartis Investigative Site
City
Esslingen
ZIP/Postal Code
73730
Country
Germany
Facility Name
Novartis Investigative Site
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Novartis Investigative Site
City
Fürth
ZIP/Postal Code
90766
Country
Germany
Facility Name
Novartis Investigative Site
City
Halle
ZIP/Postal Code
06110
Country
Germany
Facility Name
Novartis Investigative Site
City
Hamburg
ZIP/Postal Code
22457
Country
Germany
Facility Name
Novartis Investigative Site
City
Hameln
ZIP/Postal Code
31785
Country
Germany
Facility Name
Novartis Investigative Site
City
Hanau
ZIP/Postal Code
63450
Country
Germany
Facility Name
Novartis Investigative Site
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Novartis Investigative Site
City
Heilbronn
ZIP/Postal Code
74064
Country
Germany
Facility Name
Novartis Investigative Site
City
Kempten
ZIP/Postal Code
87439
Country
Germany
Facility Name
Novartis Investigative Site
City
Koeln
ZIP/Postal Code
50924
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04277
Country
Germany
Facility Name
Novartis Investigative Site
City
Muenchen
ZIP/Postal Code
81377
Country
Germany
Facility Name
Novartis Investigative Site
City
Muenchen
ZIP/Postal Code
81545
Country
Germany
Facility Name
Novartis Investigative Site
City
Muenchen
ZIP/Postal Code
81675
Country
Germany
Facility Name
Novartis Investigative Site
City
Neunkirchen
ZIP/Postal Code
66538
Country
Germany
Facility Name
Novartis Investigative Site
City
Rheinfelden/Baden
ZIP/Postal Code
79618
Country
Germany
Facility Name
Novartis Investigative Site
City
Ulm
ZIP/Postal Code
89070
Country
Germany
Facility Name
Novartis Investigative Site
City
Ulm
ZIP/Postal Code
89703
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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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

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