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

Phase 4

Completed

• Conditions: Breast Cancer
• Interventions: Drug: Docetaxel; Drug: Paclitaxel; Drug: Trastuzumab

• Registration Number: NCT01301729
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-02-09
• Study First Submitted QC: 2011-02-21
• Study First Posted: 2011-02-23
• Study Start: 2011-03
• Primary Completion: 2014-07
• Study Completion: 2014-07
• Results First Submitted: 2016-08-17
• Status Verified: 2016-11
• Results First Submitted QC: 2016-11-02
• Last Update Submitted: 2016-11-02
• Results First Posted: 2016-12-29
• Last Update Posted: 2016-12-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 32

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Trastuzumab	Paclitaxel	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.
Trastuzumab	Trastuzumab	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.
Trastuzumab	Docetaxel	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.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	From the date of informed consent to the date of death or progressive disease (up to 28 months)	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.

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate	up to 28 months	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.
Duration of Response	From the time of PR or CR until the date of PD or death (up to 28 months)	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.
Overall Survival	Time from enrollment to the date of death (up to 28 months)	Overall survival was defined as the time from the date of enrollment to the date of death due to any cause.
Percentage of Participants With an Adverse Event (AE)	Up to 28 days after last infusion of the study drug (28 months)	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.
Determination of Biomarkers Indicative for Response (Serum and Tumour Tissue Analyses)	up to 28 months
Clinical Benefit Rate	up to 28 months	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.
Time to Progression	From the date of enrollment until the date of progressive disease (up to 28 months)	Time to progression was defined as the time from the date of enrollment until the date of progressive disease.