A Study to Evaluate the Efficacy and Safety of Herceptin® (Trastuzumab) in Combination With Arimidex® (Anastrozole) an Aromatase Inhibitor Compared to Arimidex® Alone in Patients With Metastatic Breast Cancer

Phase 3

Completed

• Conditions: Breast Cancer
• Interventions: Drug: trastuzumab (Herceptin®); Drug: anastrazole (Arimidex®)

• Registration Number: NCT00022672
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This 2 arm study assessed the safety and efficacy of adding intravenous trastuzumab (Herceptin®) to daily oral anastrozole (Arimidex®) tablets as first- and second-line treatment in postmenopausal patients with human epidermal growth factor receptor-2 (HER2) overexpressing metastatic breast cancer (ER+ve and/or PR+ve). Patients were randomized to receive either anastrazole 1 mg per os (po) daily, or anastrazole 1 mg po daily + a loading dose of Herceptin® 4 mg/kg intravenous (iv) followed by weekly doses of Herceptin® 2 mg/kg iv. The anticipated time on study treatment was until disease progression, and the target sample size was 100-500 individuals.

Detailed Description

Not available

Study Timeline

• Study Start: 2001-01
• Study First Submitted: 2001-08-10
• Study First Submitted QC: 2003-01-26
• Study First Posted: 2003-01-27
• Primary Completion: 2009-10
• Study Completion: 2009-10
• Results First Submitted: 2013-04-02
• Status Verified: 2013-06
• Results First Submitted QC: 2013-06-07
• Last Update Submitted: 2013-06-07
• Results First Posted: 2013-06-13
• Last Update Posted: 2013-06-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 208

Inclusion Criteria

• postmenopausal women;
• metastatic breast cancer suitable for endocrine therapy;
• positive hormone receptor status;
• Human epidermal growth factor receptor 2 (HER2) overexpression.

Exclusion Criteria

• patients on hormone replacement therapy;
• previous chemotherapy for metastatic disease;
• uncontrolled cardiac disease and history of cardiac failure.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
trastuzumab + anastrozole	trastuzumab (Herceptin®)	Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.
trastuzumab + anastrozole	anastrazole (Arimidex®)	Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.
anastrozole	anastrazole (Arimidex®)	1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	24 Months, End of Study (Up to 5 years)	PFS was assessed by the investigator based on World Health Organization (WHO) criteria using radiographic tumor evaluations. Disease progression was defined as the appearance of any new lesion not previously identified or an estimated increase of 25% or more in existent bidimensionally or unidimensionally measurable lesions or progression of an existing non-measurable lesion. For bidimensionally measurable malignant lesions with an area of at least 2.0 centimeters squared (cm\^2) an increase of 1.0 cm\^2 was required and for unidimensionally measurable lesions of 1.0 cm or less an increase of 0.5 cm was required. PFS was defined as the number of days between date of randomization and date of documented disease progression or date of death. Kaplan Meier estimates of PFS are presented.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Clinical Benefit	24 Months, End of Study (Up to 5 years)	Clinical Benefit was defined as stable disease for ≥ six months or complete response or partial response.
Duration of Response at 24 Months	24 Months	Duration of response was defined as the number of days from the day complete response or partial response was first noted to the day of progression of disease, death or last follow-up.
Time to Response at 24 Months	24 Months	Time to response was defined as the number of days from the day of randomization to the day complete response or partial response was first noted.
Overall Survival at 24 Months	24 Months	Overall Survival is defined as the number of days from randomization to death.
Percentage of Participants With Two-Year Survival	24 Months
Percentage of Participants With Overall Tumor Response at 24 Months	24 Months	Tumor Response levels were determined by the investigator and an Independent Response Evaluation Committee and Reconciled. Overall Response was defined as either complete response or partial response.
Percentage of Participants With Best Tumor Response at 24 Months	24 Months	Tumor Response levels were determined by the investigator and an Independent Response Evaluation Committee and Reconciled. Best Response was defined as the best response a patient achieves in the study.
Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Final Visit Compared to Baseline	Baseline, Final Visit (Up to 24 Months)	Participants rated their performance status using the ECOG Questionnaire on the following scale: 0=Fully active, perform all pre-disease activities without restriction; 1=Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature; 2=Ambulatory, capable of self-care, unable to carry out any work activities, up and about more than \>50% of waking hours; 3=Capable of limited self-care, confined to bed or chair \>50% of waking hours; 4=Completely disabled, not capable of any self-care, totally confined to bed or chair; 5=Dead.; The percentage of participants in the following categories: Improved: Score decrease from baseline. Unchanged: Score the same as baseline. Worse: Score increase from baseline.
Duration of Response at End of Study	End of Study (Up to 5 years)	Duration of response was defined as the number of days from the day complete response or partial response was first noted to the day of progression of disease, death or last follow-up.
Time to Response at End of Study	End of Study (Up to 5 years)	Time to response was defined as the number of days from the day of randomization to the day complete response or partial response was first noted.
Percentage of Participants With Overall Tumor Response at End of Study	End of Study (Up to 5 years)	Tumor Response levels were determined by the investigator and an Independent Response Evaluation Committee and Reconciled. Overall Response was defined as either complete response or partial response.
Percentage of Participants With Best Tumor Response at End of Study	End of Study (Up to 5 years)	Tumor Response levels were determined by the investigator and an Independent Response Evaluation Committee and Reconciled. Best Response was defined as the best response a patient achieves in the study.
Number of Participants With Adverse Events	Throughout the Study (Up to 5 years)	Number of participants with adverse events as a measure for safety as assessed by the collection of adverse events, laboratory tests for Hematology and Serum Chemistry, clinical assessments and cardiac monitoring.