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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00375752
First received: September 11, 2006
Last updated: April 15, 2013
Last verified: April 2013
  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: Zoledronic acid
Phase 2
Phase 3

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.

  • To Compare Pathologic Complete Response (pCR) [ Time Frame: Every 6 months ] [ Designated as safety issue: No ]
  • To Compare BC Deaths and Overall Survival [ Time Frame: Every 6 months ] [ Designated as safety issue: Yes ]
  • To Compare the Quality of Life Using the FACT-B Questionnaire [ Time Frame: Every 6 months ] [ Designated as safety issue: No ]

Enrollment: 168
Study Start Date: May 2006
Estimated Study Completion Date: December 2013
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Letrozole (LET)
Letrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment.
Drug: Letrozole
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.
Other Name: Femara®)
Experimental: Letrozole +Zoledronic Acid (LET+ZOL)
2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvant treatment plus zoledronic acid 4 mg i.v. q4w
Drug: Letrozole
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.
Other Name: Femara®)
Drug: Zoledronic acid
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.
Other Name: Zometa®

  Eligibility

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

Locations
Germany
Novartis Investigative Site
Bad Saarow, Germany
Novartis Investigative Site
Berlin, Germany
Novartis Investigative Site
Brandenburg an der Havel, Germany
Novartis Investigative Site
Cottbus, Germany
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Ebersberg, Germany
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Elmshorn, Germany
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Erlangen, Germany
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Essen, Germany
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Esslingen, Germany
Novartis Investigative Site
Essn-Ruttenscheid, Germany
Novartis Investigative Site
Freiburg, Germany
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Furth, Germany
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Gifhorn, Germany
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Gorlitz, Germany
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Gottingen, Germany
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Halle, Germany
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Hameln, Germany
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Hannover, Germany
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Heilbronn, Germany
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Herne, Germany
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Homburg/Saar, Germany
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Ingolstadt, Germany
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Kempten, Germany
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Koln, Germany
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Landsberg a. Lech, Germany
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Leipzig, Germany
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Lubeck, Germany
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Mainz, Germany
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Marburg, Germany
Novartis Investigative Site
Marktredwitz, Germany
Novartis Investigative Site
Maven, Germany
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Munchen, Germany
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Mutlangen, Germany
Novartis Investigative Site
Neunkirchen, Germany
Novartis Investigative Site
Offenburg, Germany
Novartis Investigative Site
Rheinfelden, Germany
Novartis Investigative Site
Rosenheim, Germany
Novartis Investigative Site
Saarbrucken, Germany
Novartis Investigative Site
Stuttgart, Germany
Novartis Investigative Site
Ulm, Germany
Novartis Investigative Site
Wiesbaden, Germany
Novartis Investigative Site
Wolfsburg, Germany
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmeceuticals
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00375752     History of Changes
Other Study ID Numbers: CZOL446GDE19
Study First Received: September 11, 2006
Results First Received: March 30, 2012
Last Updated: April 15, 2013
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
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Letrozole
Zoledronic acid
Diphosphonates
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Bone Density Conservation Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 16, 2014