A Study of Herceptin (Trastuzumab) in Combination With a Taxane in Participants With HER2-Positive Breast Cancer Who Relapsed After (Neo)Adjuvant Herceptin Treatment

Study Overview
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Brief Summary
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This single arm, open-label study will evaluate the efficacy and safety of Herceptin (trastuzumab) in combination with a taxane as first line therapy in participants with HER2-positive breast cancer who relapsed after neoadjuvant or adjuvant Herceptin treatment. Participants will receive Herceptin (loading dose of 4 mg/kg intravenously [iv], 2 mg/kg iv weekly thereafter) with 6 3-week cycles of either docetaxel (100 mg/m2 iv every 3 weeks) or paclitaxel (90 mg/m2 every week). Herceptin treatment will be continued until disease progression or unacceptable toxicity occurs.

Official Title
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A Multicenter, Single Arm, Open-Label PhIV Study to Investigate the Effect of First-Line Herceptin (Trastuzumab) in Combination With a Taxane in Patients With Metastatic Breast Cancer Who Relapsed After Receiving (Neo)Adjuvant Herceptin for HER2-Positive Early Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Paclitaxel
* Drug: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female participants , >/= 18 years of age Locally recurrent/metastatic breast cancer (relapse in supra- or infraclavicular lymph nodes is regarded as metastatic disease) HER2-positive primary disease Participants must have received Herceptin in the adjuvant and/or neoadjuvant setting Relapsed breast cancer >/= 6 months after discontinuing last drugs of Herceptin and/or chemotherapy in the adjuvant and/or neoadjuvant setting for HER2-positive breast cancer Measurable disease according to RECIST 1.0 Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Maximum cumulative dose of doxorubicin </= 360 mg/m2 or of epirubicin </= 720 mg/m2 or no prior anthracyclines At least 3 weeks after prior surgery or radiotherapy Exclusion Criteria: Pregnant or breastfeeding women Previous chemotherapy for metastatic breast cancer (prior endocrine therapy till progressive disease is allowed) Pleural effusions, ascites or bone lesions as only manifestation of disease Brain metastases Invasive malignancy other than metastatic breast cancer Inadequate bone marrow, hepatic or renal function Prior treatment with anti-HER therapies other than (neo)adjuvant Herceptin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trastuzumab<br>Participants with metastatic breast cancer received a loading dose of 4 milligrams per kilograms (mg/kg) of trastuzumab intravenously (IV) followed by 2 mg/kg of trastuzumab IV once a week along with docetaxel 100 milligrams per meter square (mg/m^2), every 3 weeks or paclitaxel 90 mg/m^2 once a week until progression of disease, occurrence of intolerable toxicity, the participant discontinues the study or dies. | Drug: Docetaxel<br>* 100 mg/m2 iv every 3 weeks, 6 cycles (18 weeks)<br>Drug: Paclitaxel<br>* 90 mg/kg iv (+/-10%) every 3 weeks for 6 3-week cycles (18 weeks)<br>Drug: Trastuzumab<br>* 4 mg/kg iv loading dose on Day 1, 2 mg/kg iv on Day 8 and weekly thereafter<br>* Other names: Herceptin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.0 and was defined as the time from the date when the participant signed the informed consent form (ICF) until death or progressive disease (PD). PD was defined as 20% increase in the sum of the longest diameter of target lesions. PFS and associated confidence intervals were calculated using the Kaplan-Meier method. | From the date of informed consent to the date of death or progressive disease (up to 28 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Overall response rate was assessed using RECIST 1.0 and defined as the percentage of participants that achieved a complete response (CR) or a partial response (PR). CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. | up to 28 months | 
| Duration of Response | Duration of response was defined as the time from when a PR or CR was first documented until the date of documented PD or death. CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. PD was defined as 20% increase in the sum of the longest diameter of target lesions. | From the time of PR or CR until the date of PD or death (up to 28 months) | 
| Overall Survival | Overall survival was defined as the time from the date of enrollment to the date of death due to any cause. | Time from enrollment to the date of death (up to 28 months) | 
| Percentage of Participants With an Adverse Event (AE) | An AE was defined as any adverse medical event that occurred after the participant used the investigational medicinal product (IMP) or other intervention behaviors specified by the protocol in the clinical trial regardless of relationship to the study treatment. | Up to 28 days after last infusion of the study drug (28 months) | 
| Determination of Biomarkers Indicative for Response (Serum and Tumour Tissue Analyses) |  | up to 28 months | 
| Clinical Benefit Rate | Clinical benefit rate was assessed according to RECIST 1.0 and defined as the percentage of participants who experienced a CR, PR, or stable disease (SD) for at least 6 months. CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. SD was defined as small changes that do not meet above criteria. | up to 28 months | 
| Time to Progression | Time to progression was defined as the time from the date of enrollment until the date of progressive disease. | From the date of enrollment until the date of progressive disease (up to 28 months) |