Brief Summary
This is a multicenter phase 2 study designed to evaluate the safety and efficacy of eribulin mesylate in combination with trastuzumab as first line treatment in female subjects with locally recurrent or metastatic human epidermal growth factor receptor (HER2) positive breast cancer.
Brief Title
Eribulin With Trastuzumab as First-line Therapy for Locally Recurrent or Metastatic HER2 Positive Breast Cancer
Categories
Completion Date
Completion Date Type
Actual
Conditions
Breast Cancer
Eligibility Criteria
Key Inclusion criteria:
* Age 18 years or older
* Histologically or cytologically proven adenocarcinoma of the breast
* Subjects who have locally recurrent or metastatic disease with at least one measurable lesion
* HER2 positive as determined by score of 3 on immunohistochemistry (IHC) staining or gene amplification by fluorescence in situ hybridization (FISH).
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0, 1 or 2
* At least 12 months since prior neoadjuvant or adjuvant chemotherapy
* At least 2 weeks since prior radiotherapy, endocrine therapy, trastuzumab, or lapatinib, with complete recovery from the effects of these interventions
* Adequate renal function
* Adequate bone marrow function
* Adequate liver function
* Adequate cardiac function
Key Exclusion criteria:
* Prior chemotherapy, biologic therapy, or investigational therapy for locally recurrent or metastatic HER2 breast cancer.
* Subjects who have had a prior malignancy other than carcinoma in situ of the cervix, or nonmelanoma skin cancer
* Prior exposure to greater than 360 mg/m2 doxorubicin or liposomal doxorubicin, greater than 120 mg/m2 mitoxantrone, greater than 90 mg/m2 idarubicin, or greater than 720 mg/m2 epirubicin
* Inflammatory breast cancer
* Prior history of hypertensive crisis or hypertensive encephalopathy
* Clinically significant cardiovascular impairment
* Subjects with known central nervous system (CNS) disease are not eligible, except for those subjects with treated brain metastasis.
* Subjects with metastatic disease limited to bone are ineligible unless there is at least one lytic lesion with identifiable soft tissue components that can be evaluated by computed tomography (CT) or magnetic resonance imaging (MRI)
* Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring the use of oxygen
* History of bleeding diasthesis
* Currently pregnant or breast-feeding.
* Subjects with preexisting Grade 3 or 4 neuropathy. Any peripheral neuropathy must recover to Grade less than or equal to 2 before enrollment
* Age 18 years or older
* Histologically or cytologically proven adenocarcinoma of the breast
* Subjects who have locally recurrent or metastatic disease with at least one measurable lesion
* HER2 positive as determined by score of 3 on immunohistochemistry (IHC) staining or gene amplification by fluorescence in situ hybridization (FISH).
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0, 1 or 2
* At least 12 months since prior neoadjuvant or adjuvant chemotherapy
* At least 2 weeks since prior radiotherapy, endocrine therapy, trastuzumab, or lapatinib, with complete recovery from the effects of these interventions
* Adequate renal function
* Adequate bone marrow function
* Adequate liver function
* Adequate cardiac function
Key Exclusion criteria:
* Prior chemotherapy, biologic therapy, or investigational therapy for locally recurrent or metastatic HER2 breast cancer.
* Subjects who have had a prior malignancy other than carcinoma in situ of the cervix, or nonmelanoma skin cancer
* Prior exposure to greater than 360 mg/m2 doxorubicin or liposomal doxorubicin, greater than 120 mg/m2 mitoxantrone, greater than 90 mg/m2 idarubicin, or greater than 720 mg/m2 epirubicin
* Inflammatory breast cancer
* Prior history of hypertensive crisis or hypertensive encephalopathy
* Clinically significant cardiovascular impairment
* Subjects with known central nervous system (CNS) disease are not eligible, except for those subjects with treated brain metastasis.
* Subjects with metastatic disease limited to bone are ineligible unless there is at least one lytic lesion with identifiable soft tissue components that can be evaluated by computed tomography (CT) or magnetic resonance imaging (MRI)
* Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring the use of oxygen
* History of bleeding diasthesis
* Currently pregnant or breast-feeding.
* Subjects with preexisting Grade 3 or 4 neuropathy. Any peripheral neuropathy must recover to Grade less than or equal to 2 before enrollment
Inclusion Criteria
Inclusion criteria:
* Age 18 years or older
* Histologically or cytologically proven adenocarcinoma of the breast
* Subjects who have locally recurrent or metastatic disease with at least one measurable lesion
* HER2 positive as determined by score of 3 on immunohistochemistry (IHC) staining or gene amplification by fluorescence in situ hybridization (FISH).
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0, 1 or 2
* At least 12 months since prior neoadjuvant or adjuvant chemotherapy
* At least 2 weeks since prior radiotherapy, endocrine therapy, trastuzumab, or lapatinib, with complete recovery from the effects of these interventions
* Adequate renal function
* Adequate bone marrow function
* Adequate liver function
* Adequate cardiac function
* Age 18 years or older
* Histologically or cytologically proven adenocarcinoma of the breast
* Subjects who have locally recurrent or metastatic disease with at least one measurable lesion
* HER2 positive as determined by score of 3 on immunohistochemistry (IHC) staining or gene amplification by fluorescence in situ hybridization (FISH).
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0, 1 or 2
* At least 12 months since prior neoadjuvant or adjuvant chemotherapy
* At least 2 weeks since prior radiotherapy, endocrine therapy, trastuzumab, or lapatinib, with complete recovery from the effects of these interventions
* Adequate renal function
* Adequate bone marrow function
* Adequate liver function
* Adequate cardiac function
Gender
Female
Gender Based
false
Keywords
Locally recurrent
metastatic HER2Positive breast cancer
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01269346
Org Class
Industry
Org Full Name
Eisai Inc.
Org Study Id
E7389-A001-208
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 2, Multicenter, Single-Arm Study of Eribulin Mesylate With Trastuzumab as First-Line Therapy for Locally Recurrent or Metastatic Human Epidermal Growth Factor Receptor Two (HER2) Positive Breast Cancer
Primary Outcomes
Outcome Description
The Objective Response Rate (Complete Response plus Partial Response, (CR + PR)) was defined as the proportion of participants who have a best overall response of confirmed CR or PR based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the Investigator. Tumor assessment was by computed tomography (CT)/magnetic resonance imaging (MRI). To assess best response (CR, PR, stable disease (SD), progressive disease (PD), or not estimable (NE)), the Investigator selected up to five measurable target lesions (2 per organ). All other lesions were identified as nontarget lesions. Each participant's overall tumor burden at Baseline was compared with subsequent measurements of the target lesions. For participants with CR or PR, changes in tumor sizes had to be confirmed by repeat evaluations performed not fewer than four weeks after the initial response assessment.
Outcome Measure
Objective Response Rate
Outcome Time Frame
Baseline (within 28 days of first infusion of study drug); Treatment Phase (every 6 weeks during the first 6 cycles); Extension Phase (every 12 weeks) to PR or CR
Secondary Outcomes
Outcome Description
Time to first response was defined for participants whose best overall response was a CR or PR.
Outcome Time Frame
From date of first dose of study drug to the earliest date that CR or PR was objectively documented, assessed up to data cutoff (12 Sep 2013), up to approximately 2 years 9 months
Outcome Measure
Time to First Response
Outcome Description
Duration of response was defined for participants whose best overall response was CR or PR. Participants who died without reported PD were considered to have progressed on the day of their death. Participants who were alive at the end of the study without reported PD were censored on the date of their last tumor assessment.
Outcome Time Frame
Date of a confirmed CR or PR was first documented to the date of PD or death (due to any cause and in the absence of PD), whichever occurred first, or date of data cutoff (12 Sep 2013), or up to approximately 2 years 9 months
Outcome Measure
Duration of Response (DOR)
Outcome Description
PFS was defined as the time from the date of the first dose of study drug until the date of first documentation of PD or date of death from any cause, whichever occurred first. Participants who died without reported PD were considered to have progressed on the day of their death. Participants who were lost to follow-up or alive and without reported PD at the end of study were censored on the date of their last tumor assessment.
Outcome Time Frame
Date of first dose of study drug to date of PD or death (from any cause) whichever came first, or date of data cutoff (12 Sep 2013), up to approximately 2 years 9 months
Outcome Measure
Progression-Free Survival (PFS)
Outcome Description
Defined as the period from treatment start date to the date of PD or death, whichever occurred first. Participants who were alive without having PD as of the data cutoff date were censored as of their last tumor assessment. Calculated for participants who best response was SD.
Outcome Time Frame
Start of study treatment to date of PD or death, whichever occurred first, or date of data cutoff (12 Sep 2013), up to approximately 2 years 9 months
Outcome Measure
Duration of Stable Disease (SD)
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Joseph Sparano
Investigator Email
jsparano@montefiore.org
Investigator Phone
718-405-8404