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

NCT00375752 | Terminated Phase 4 Results

• 2 other identifiers: CZOL446GDE192004-004007-37
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 27

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

Conditions

Breast Neoplasms

Keywords

Breast cancer; Anti tumor potential; Letrozole; Zoledronic acid; Neoadjuvant treatment; Hormone responsive breast cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Secondary Outcomes (4)

• Best RECIST Response Based on Central Review at 6 Mos

  6 Months

• Number of Patients With Breast Conserving Surgery at 6 Months

  Every 6 months

• Change From Baseline in Tumor Size (Longest Diameter) at Month 6

  Baseline, Month 6

• Mean Changes From Baseline in FACT-B Total Score at 6 Months (ITT, Data as Observed)

  baseline and 6 mos

Study Arms (2)

Letrozole

ACTIVE COMPARATOR

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

Drug: Letrozole

Zolendronic Acid + Letrozole

EXPERIMENTAL

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

Drug: Letrozole; Drug: Zolendronic Acid

Interventions

Letrozole DRUG

2.5 mg.tablet.

Letrozole; Zolendronic Acid + Letrozole

Zolendronic Acid 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)

Zolendronic Acid + Letrozole

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (27)

Novartis Investigative Site

Amberg, 92224, Germany

Location

Novartis Investigative Site

Berlin, 10365, Germany

Location

Novartis Investigative Site

Böblingen, 71032, Germany

Location

Novartis Investigative Site

Celle, 29223, Germany

Location

Novartis Investigative Site

Cologne, 50924, Germany

Location

Novartis Investigative Site

Ebersberg, 85560, Germany

Location

Novartis Investigative Site

Erlangen, 91052, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Essen, 45276, Germany

Location

Novartis Investigative Site

Esslingen am Neckar, 73730, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Fürth, 90766, Germany

Location

Novartis Investigative Site

Halle, 06110, Germany

Location

Novartis Investigative Site

Hamburg, 22457, Germany

Location

Novartis Investigative Site

Hamelin, 31785, Germany

Location

Novartis Investigative Site

Hanau, 63450, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Heilbronn, 74064, Germany

Location

Novartis Investigative Site

Kempten, 87439, Germany

Location

Novartis Investigative Site

Leipzig, 04277, Germany

Location

Novartis Investigative Site

München, 81377, Germany

Location

Novartis Investigative Site

München, 81545, Germany

Location

Novartis Investigative Site

München, 81675, Germany

Location

Novartis Investigative Site

Neunkirchen, 66538, Germany

Location

Novartis Investigative Site

Rheinfelden, 79618, Germany

Location

Novartis Investigative Site

Ulm, 89070, Germany

Location

Novartis Investigative Site

Ulm, 89703, Germany

Location

Related Publications (1)

• 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.

  PMID: 38979716 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Study terminated after 178 patients screened and 168 randomized, due to insufficient recruitment rate (no safety issues decided the reason to terminate study). LPLV for study was on 13-DEC-2010. LPLV of the 5-year follow-up period was on 03-FEB-2016.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

• Novartis Pharmaceuticals

  Novartis Pharmeceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Open-label, multicenter, randomized
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2006
• First Posted: September 13, 2006
• Study Start: June 1, 2006
• Primary Completion: December 16, 2010
• Study Completion: December 16, 2010
• Last Updated: June 26, 2017
• Results First Posted: April 25, 2012

Record last verified: 2017-06

Locations

DE (27)