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

• ClinicalTrials.gov Identifier: NCT00375752
• Recruitment Status: Terminated
• First Posted: September 13, 2006
• Results First Posted: April 25, 2012
• Last Update Posted: June 26, 2017
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

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

Condition or disease	Intervention/treatment	Phase
Breast Neoplasms	Drug: Letrozole; Drug: Zolendronic Acid	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 168 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Open-label, multicenter, randomized
• 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)
• Actual Study Start Date: June 1, 2006
• Actual Primary Completion Date: December 16, 2010
• Actual Study Completion Date: December 16, 2010

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Letrozole; Letrozole 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvent treatment	Drug: Letrozole; 2.5 mg.tablet.
Experimental: Zolendronic Acid + Letrozole; 2.5 mg/day oral letrozole for approximately 6.5 months neoadjuvant treatment plus zoledronic acid 4 mg i.v. q4w	Drug: Letrozole; 2.5 mg.tablet.; 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)

Outcome Measures

Primary Outcome Measures :

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 [ Time Frame: 6 months ]
   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 :

1. Best RECIST Response Based on Central Review at 6 Mos [ Time Frame: 6 Months ]
   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.
2. Number of Patients With Breast Conserving Surgery at 6 Months [ Time Frame: Every 6 months ]
3. Change From Baseline in Tumor Size (Longest Diameter) at Month 6 [ Time Frame: Baseline, Month 6 ]
   Tumor size (sum of longest diameter)was analyzed based on the diameters values provided with the central review.
4. Mean Changes From Baseline in FACT-B Total Score at 6 Months (ITT, Data as Observed) [ Time Frame: baseline and 6 mos ]

   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)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes 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

Locations

Germany

Novartis Investigative Site

Amberg, Germany, 92224

Novartis Investigative Site

Berlin, Germany, 10365

Novartis Investigative Site

Boeblingen, Germany, 71032

Novartis Investigative Site

Celle, Germany, 29223

Novartis Investigative Site

Ebersberg, Germany, 85560

Novartis Investigative Site

Erlangen, Germany, 91052

Novartis Investigative Site

Essen, Germany, 45147

Novartis Investigative Site

Essen, Germany, 45276

Novartis Investigative Site

Esslingen, Germany, 73730

Novartis Investigative Site

Freiburg, Germany, 79106

Novartis Investigative Site

Fürth, Germany, 90766

Novartis Investigative Site

Halle, Germany, 06110

Novartis Investigative Site

Hamburg, Germany, 22457

Novartis Investigative Site

Hameln, Germany, 31785

Novartis Investigative Site

Hanau, Germany, 63450

Novartis Investigative Site

Hannover, Germany, 30625

Novartis Investigative Site

Heilbronn, Germany, 74064

Novartis Investigative Site

Kempten, Germany, 87439

Novartis Investigative Site

Koeln, Germany, 50924

Novartis Investigative Site

Leipzig, Germany, 04277

Novartis Investigative Site

Muenchen, Germany, 81377

Novartis Investigative Site

Muenchen, Germany, 81545

Novartis Investigative Site

Muenchen, Germany, 81675

Novartis Investigative Site

Neunkirchen, Germany, 66538

Novartis Investigative Site

Rheinfelden/Baden, Germany, 79618

Novartis Investigative Site

Ulm, Germany, 89070

Novartis Investigative Site

Ulm, Germany, 89703

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals
• Study Director: Novartis Pharmaceuticals; Novartis Pharmeceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00375752
• Other Study ID Numbers: CZOL446GDE19; 2004-004007-37 ( EudraCT Number )
• First Posted: September 13, 2006
• Results First Posted: April 25, 2012
• Last Update Posted: June 26, 2017
• Last Verified: June 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

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

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Letrozole; Antineoplastic Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs