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

A Randomized, Open-label Study of the Effect of Herceptin Plus Arimidex Compared With Arimidex Alone on Progression-free Survival in Patients With HER2-positive and Hormone-receptor Positive Metastatic Breast Cancer

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: trastuzumab (Herceptin®); Drug: anastrazole (Arimidex®)

• Study Type: Interventional
• Enrollment (Actual): 208
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia, 3128
  • Darlinghurst, Australia, 2010
  • Waratah, Australia, 2298
• Brazil
  • Porto Alegre, Brazil, 90610-000
• Bulgaria
  • Plovdiv, Bulgaria, 4000
  • Sofia, Bulgaria, 1527
  • Stara Zagora, Bulgaria, 8000
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
    • Edmonton, Alberta, Canada, T6G 1Z2
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 6V5
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
  • Ontario
    • Oshawa, Ontario, Canada, L1G 2B9
    • Toronto, Ontario, Canada, M5G 2M9
    • Toronto, Ontario, Canada, M4N 3M5
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
    • Quebec City, Quebec, Canada, G1S 4L8
• China
  • Beijing, China, 100021
  • Beijing, China, 100071
  • Shanghai, China, 200032
  • Shanghai, China, 200025
  • Wuhan, China, 430030
• France
  • Avignon, France, 84082
  • Nice, France, 06189
• Germany
  • Frankfurt, Germany, 60596
  • Kiel, Germany, 24105
  • München, Germany, 80637
  • Trier, Germany, 54290
• Hong Kong
  • Hong Kong, Hong Kong
• Hungary
  • Budapest, Hungary, H-1122
• India
  • Ahmedabad, India, 380 016
  • Bangalore, India, 560 029
  • Chennai, India, 600 020
  • Cuttack, India, 753 007
  • Ludhiana, India, 141 001
  • Mumbai, India, 400012
  • New Delhi, India, 110 029
  • New Delhi, India, 110 060
  • New Delhi, India, 110085
• Israel
  • Haifa, Israel, 34362
  • Haifa, Israel, 31096
  • Petach Tikva, Israel, 49100
  • Ramat-gan, Israel, 52621
  • Rehovot, Israel, 76100
  • Tel Aviv, Israel, 64239
• Italy
  • Genova, Italy, 16132
• Lithuania
  • Vilnius, Lithuania, 2600
• Mexico
  • Guadalajara, Mexico, 44340
  • Mexico City, Mexico, 14000
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
  • Rotterdam, Netherlands, 3075 EA
• Norway
  • Trondheim, Norway, 7006
• Poland
  • Bialystok, Poland, 15-027
  • Bydgoszcz, Poland, 85-796
  • Gliwice, Poland, 44-101
  • Krakow, Poland, 31-115
  • Lodz, Poland, 94-306
  • Szczecin, Poland, 71-730
  • Warszawa, Poland, 00-909
  • Warszawa, Poland, 02-781
• Russian Federation
  • Barnaul, Russian Federation, 656049
  • Izhevsk, Russian Federation, 426009
  • Kazan, Russian Federation, 420029
  • Krasnodar, Russian Federation, 350080
  • Moscow, Russian Federation, 107005
  • Moscow, Russian Federation, 125284
  • Moscow, Russian Federation, 115478
  • Moscow, Russian Federation, 121356
  • Moscow, Russian Federation, 117837
  • St Petersburg, Russian Federation, 197022
  • St Petersburg, Russian Federation, 197758
  • St Petersburg, Russian Federation, 189646
  • UFA, Russian Federation, 450054
• South Africa
  • Floracliffe, South Africa, 1715
  • Pretoria, South Africa
• Spain
  • Barcelona, Spain, 08036
  • Córdoba, Spain, 14004
  • Girona, Spain, 17007
  • Madrid, Spain, 28034
  • Madrid, Spain, 28041
  • Madrid, Spain, 28007
  • Mataro, Spain, 08304
  • Reus, Spain, 43204
  • Valencia, Spain, 46009
• Sweden
  • Boras, Sweden, 50182
  • Gaelve, Sweden, 80187
  • Stockholm, Sweden, 17176
  • Örebro, Sweden, 701 85
• Taiwan
  • Taipei, Taiwan, 112
  • Taoyuan, Taiwan, 333
• Turkey
  • Ankara, Turkey, 06500
  • Ankara, Turkey, 06230
  • Istanbul, Turkey, 34300
  • Istanbul, Turkey, 34390
  • Izmir, Turkey, 35100
  • Shhiye, Ankara, Turkey, 06100
• Ukraine
  • Kiev, Ukraine
  • Kiev, Ukraine, 03022
  • Lvov, Ukraine, 79031
  • Odessa, Ukraine, 65055
  • Sumy, Ukraine, 40005
  • Zaporozhye, Ukraine, 69104
• United Kingdom
  • Cardiff, United Kingdom, CF14 2TL
  • Edinburgh, United Kingdom, EH4 2XU
  • Guildford, United Kingdom, GU2 7XX
  • Ipswich, United Kingdom, IP4 5PD
  • London, United Kingdom, SE1 9RT
  • London, United Kingdom, NW3 2QG
  • Manchester, United Kingdom, M20 4BX
  • Merseyside, United Kingdom, CH63 45Y
  • Newcastle Upon Tyne, United Kingdom, NE4 6BE
  • Southampton, United Kingdom, SO16 6YD
  • Swansea, United Kingdom, SA2 8QA
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
  • Arkansas
    • Little Rock, Arkansas, United States, 72205-7199
  • California
    • Los Angeles, California, United States, 90048
    • Vallejo, California, United States, 94589
  • Florida
    • Gainsville, Florida, United States, 32605
    • Miami, Florida, United States, 33176
    • Plantation, Florida, United States, 33324
  • Illinois
    • Chicago, Illinois, United States, 60637
    • Chicago, Illinois, United States, 60612
  • Kansas
    • Kansas City, Kansas, United States, 66160
  • Maine
    • Scarborough, Maine, United States, 04074
  • Michigan
    • Detroit, Michigan, United States, 48202-2689
  • Nebraska
    • Omaha, Nebraska, United States, 68114
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-5636
    • Santa Fe, New Mexico, United States, 87505
  • New York
    • Rochester, New York, United States, 14642
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0562
    • Cleveland, Ohio, United States, 44106
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-0850

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: trastuzumab + anastrozole; 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.	Drug: trastuzumab (Herceptin®); 4mg/kg iv loading dose, followed by 2mg/kg iv weekly; Other Names: Herceptin®; Drug: anastrazole (Arimidex®); 1 mg tablet taken orally daily; Other Names: Arimidex®
Active Comparator: anastrozole; 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.	Drug: anastrazole (Arimidex®); 1 mg tablet taken orally daily; Other Names: Arimidex®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	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.	24 Months, End of Study (Up to 5 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clinical Benefit	Clinical Benefit was defined as stable disease for ≥ six months or complete response or partial response.	24 Months, End of Study (Up to 5 years)
Duration of Response at 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.	24 Months
Time to Response at 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.	24 Months
Overall Survival at 24 Months	Overall Survival is defined as the number of days from randomization to death.	24 Months
Percentage of Participants With Two-Year Survival		24 Months
Percentage of Participants With Overall Tumor Response at 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.	24 Months
Percentage of Participants With Best Tumor Response at 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.	24 Months
Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Final Visit Compared to Baseline	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.	Baseline, Final Visit (Up to 24 Months)
Duration of Response at End of Study	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.	End of Study (Up to 5 years)
Time to Response at End of Study	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.	End of Study (Up to 5 years)
Percentage of Participants With Overall Tumor Response at End of Study	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.	End of Study (Up to 5 years)
Percentage of Participants With Best Tumor Response at End of Study	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.	End of Study (Up to 5 years)
Number of Participants With Adverse Events	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.	Throughout the Study (Up to 5 years)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Collaborators: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: January 1, 2001
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: August 10, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): June 13, 2013
• Last Update Submitted That Met QC Criteria: June 7, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Trastuzumab; Anastrozole
• Other Study ID Numbers: BO16216