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

NCT ID: NCT00375752

Last Updated: 2017-06-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 168 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-01
• Study Completion Date: 2010-12-16

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.

Conditions

Breast Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Letrozole

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

Group Type: ACTIVE_COMPARATOR

Letrozole

Intervention Type: DRUG

2.5 mg.tablet.

Zolendronic Acid + Letrozole

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

Group Type: EXPERIMENTAL

Letrozole

Intervention Type: DRUG

2.5 mg.tablet.

Zolendronic Acid

Intervention Type: DRUG

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)

Interventions

Letrozole

2.5 mg.tablet.

Intervention Type: 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)

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmeceuticals

Locations

Novartis Investigative Site

Amberg, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Böblingen, , Germany

Novartis Investigative Site

Celle, , Germany

Novartis Investigative Site

Cologne, , Germany

Novartis Investigative Site

Ebersberg, , Germany

Novartis Investigative Site

Erlangen, , Germany

Novartis Investigative Site

Essen, , Germany

Novartis Investigative Site

Essen, , Germany

Novartis Investigative Site

Esslingen am Neckar, , Germany

Novartis Investigative Site

Freiburg im Breisgau, , Germany

Novartis Investigative Site

Fürth, , Germany

Novartis Investigative Site

Halle, , Germany

Novartis Investigative Site

Hamburg, , Germany

Novartis Investigative Site

Hamelin, , Germany

Novartis Investigative Site

Hanau, , Germany

Novartis Investigative Site

Hanover, , Germany

Novartis Investigative Site

Heilbronn, , Germany

Novartis Investigative Site

Kempten, , Germany

Novartis Investigative Site

Leipzig, , Germany

Novartis Investigative Site

München, , Germany

Novartis Investigative Site

München, , Germany

Novartis Investigative Site

München, , Germany

Novartis Investigative Site

Neunkirchen, , Germany

Novartis Investigative Site

Rheinfelden, , Germany

Novartis Investigative Site

Ulm, , Germany

Novartis Investigative Site

Ulm, , Germany

Countries

Germany

References

Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.

Reference Type: DERIVED

PMID: 38979716 (View on PubMed)

Other Identifiers

2004-004007-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CZOL446GDE19

Identifier Type: -

Identifier Source: org_study_id