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

Breast Neoplasms Clinical Trial

— 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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00375752
• Other study ID #: CZOL446GDE19
• Secondary ID: 2004-004007-37
• Status: Terminated
• Phase: Phase 4
• First received: September 11, 2006
• Last updated: June 6, 2017
• Start date: June 1, 2006
• Est. completion date: December 16, 2010

Study information

• Verified date: June 2017
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 168
• Est. completion date: December 16, 2010
• Est. primary completion date: December 16, 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• Letrozole
2.5 mg.tablet.
• 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)

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Amberg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Boeblingen
Germany	Novartis Investigative Site	Celle
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
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Fürth
Germany	Novartis Investigative Site	Halle
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hameln
Germany	Novartis Investigative Site	Hanau
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heilbronn
Germany	Novartis Investigative Site	Kempten
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Neunkirchen
Germany	Novartis Investigative Site	Rheinfelden/Baden
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Ulm

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	6 Months
Secondary	Number of Patients With Breast Conserving Surgery at 6 Months		Every 6 months
Secondary	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.	Baseline, Month 6
Secondary	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)	baseline and 6 mos

External Links

•   Find Trial Results for CZOL446GDE19 at Novartis Clinical Trials