Breast Cancer
Conditions
Keywords
Breast Cancer
Brief summary
The purpose of the study is to evaluate dose limiting toxicity (DLT), investigate the tolerability and safety of eribulin mesylate with trastuzumab combination therapy, and estimate the recommended dose.
Interventions
DRUGE7389
Eribulin mesylate (iv) will be administered on Day 1 and Day 8 of each cycle (3 weeks as 1 cycle). Trastuzumab (iv) will be administered as weekly use or tri-weekly use. Trastuzumab will be administered immediately after eribulin mesylate administration when used concomitantly.
Sponsors
Eisai Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Females aged greater than or equal to 20 years and less than 75 years at the time of informed consent. * Histologically or cytologically confirmed with breast cancer * Score 3+ by immunohistochemistry (IHC) or HER2 positive by Fluorescence in Situ Hybridization (FISH) method * Subjects who meet any of the following criteria: * Evidence of recurrence during adjuvant chemotherapy with trastuzumab and taxane * Evidence of recurrence within 6 months after adjuvant chemotherapy with trastuzumab and taxane * Experienced prior chemotherapy including trastuzumab and taxane for advanced or recurrent breast cancer * Adequate organ function * Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS) is 0 or 1 * Subjects who have submitted written informed consent for study entry
Exclusion criteria
* Subjects with known brain metastasis accompanied by clinical symptoms or requiring active treatment * Subjects with severe active infection requiring active treatment * Subjects with large pleural effusions, ascites, or pericardial effusions requiring drainage. * Hypersensitivity to trastuzumab, halicondrin B or halicondrin B chemical derivatives * Known positive for human immunodeficiency virus (HIV) test or positive for hepatitis B surface (HBs antigen) or hepatitis C (HCV) by serum test. * Subjects who are pregnant (positive B-hCG test) or breastfeeding * Subjects judged to be ineligible for this study by the principal investigator or sub-investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicity (DLT) | Up to 3 weeks | For DLT evaluation, severity (grade) was classified according to common terminology criteria for adverse events version 4.0 (CTCAE v4.0). DLTs were defined as grade 4 neutropenia persisting for more than 7 days; grade 3 or above febrile neutropenia; grade 4 thrombocytopenia or grade 3 thrombocytopenia requiring blood transfusion; non-hematologic toxicity (excluding toxicity related to neutrophils, leukocytes, lymphocytes, platelets, CD4 lymphocytes, anemia, and bone marrow density) greater than or equal to grade 3 (Exceptions: Dose reduction was not required even when the following conditions were met: grade 3 nausea, vomiting, or diarrhea controllable with anti-emetic or anti-diarrheal medication and abnormal laboratory parameter not requiring treatment); and day 8 administration was delayed or skipped as a result of the subject did not meet the dosing riteria within cycle. |
| Number of Participants With Adverse Events | From signing of informed consent up to 30 days after participant's last treatment dose or up to approximately 2 years | The number of subjects who developed 'treatment-emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| E7389 With Weekly Trastuzumab Eribulin mesylate (E7389) was administered intravenously on Day 1 and Day 8 of each 3 week cycle. Trastuzumab was administered intravenously weekly, with an initial dose of 4 mg/kg followed by 2 mg/kg for the remaining doses. | 6 |
| E7389 With Tri-weekly Trastuzumab Eribulin mesylate (E7389) was administered intravenously on Day 1 and Day 8 of each 3 week cycle. Trastuzumab was administered intravenously tri-weekly, with an initial dose of 8 mg/kg followed by 6 mg/kg for the remaining doses. | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | E7389 With Weekly Trastuzumab | E7389 With Tri-weekly Trastuzumab | Total |
|---|---|---|---|
| Age, Continuous | 64.7 Years STANDARD_DEVIATION 5.05 | 49.2 Years STANDARD_DEVIATION 10.32 | 56.9 Years STANDARD_DEVIATION 11.2 |
| Race/Ethnicity, Customized Japanese | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants With Adverse Events
The number of subjects who developed 'treatment-emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Time frame: From signing of informed consent up to 30 days after participant's last treatment dose or up to approximately 2 years
Population: The safety analysis set included all participants who received at least one dose of study drug and had at least one post dose safety evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E7389 With Weekly Trastuzumab | Number of Participants With Adverse Events | 6 Participants |
| E7389 With Tri-weekly Trastuzumab | Number of Participants With Adverse Events | 6 Participants |
Primary
Number of Participants With Dose Limiting Toxicity (DLT)
For DLT evaluation, severity (grade) was classified according to common terminology criteria for adverse events version 4.0 (CTCAE v4.0). DLTs were defined as grade 4 neutropenia persisting for more than 7 days; grade 3 or above febrile neutropenia; grade 4 thrombocytopenia or grade 3 thrombocytopenia requiring blood transfusion; non-hematologic toxicity (excluding toxicity related to neutrophils, leukocytes, lymphocytes, platelets, CD4 lymphocytes, anemia, and bone marrow density) greater than or equal to grade 3 (Exceptions: Dose reduction was not required even when the following conditions were met: grade 3 nausea, vomiting, or diarrhea controllable with anti-emetic or anti-diarrheal medication and abnormal laboratory parameter not requiring treatment); and day 8 administration was delayed or skipped as a result of the subject did not meet the dosing riteria within cycle.
Time frame: Up to 3 weeks
Population: The DLT analysis set included those participants who received at least one dose of study drug and had a DLT assessment in cycle 1 (3 weeks) without deviations from the eribulin mesylate/trastuzumab dosing regimens and other major protocol prescripts. Participants with a DLT, regardless of this criterion, were also included in the DLT analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E7389 With Weekly Trastuzumab | Number of Participants With Dose Limiting Toxicity (DLT) | 0 Participants |
| E7389 With Tri-weekly Trastuzumab | Number of Participants With Dose Limiting Toxicity (DLT) | 0 Participants |