Breast Cancer, Breast Neoplasms
Conditions
Keywords
Breast Cancer, Metastatic
Brief summary
This clinical study is designed as an open, single group, multi-center, phase 4 clinical study to assess the safety of eribulin which is approved for the treatment of the patients in Korea with locally advanced or metastatic breast cancer who had received two to five prior chemotherapy regimens including anthracyclines and taxanes for advanced disease. Subjects who meet the inclusion/exclusion criteria are administered of 1.4 mg/m2 of the investigational product intravenously in 2-5 min on day 1 and day 8 of every 21-day cycle. In case of the progression of disease, unacceptable toxicity, withdrawal of the consent, or judgment by investigator that the treatment needs to be stopped, the treatment of investigational product is stopped, and treatment termination assessment is performed within 30 days from the last treatment.
Interventions
DRUGEribulin mesylate
1.4 mg/m2 (as eribulin 1.23 mg/m2) day by 2-5 minutes IV on Day 1 and 8 every 21 days
Sponsors
Eisai Korea Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Female, Age greater or equal to 20 years 2. Patients with histologically or cytologically confirmed carcinoma of the breast 3. Patients with locally advance or metastatic carcinoma of the breast 4. Patients who have received two to five prior chemotherapeutic regimens including an antracycline and a taxane and 2 or more regimens for locally recurrent and/or metastatic disease 5. Patients must have proved refractory to the most recent chemotherapy on or within six (6) months of therapy 6. Patients who have assessable lesion according to RECIST v 1.1 7. Adequately maintained bone marrow function * absolute neutrophil count (ANC) greater than or equal to 1.5 x 10\^9 /L * hemoglobin greater than or equal to 10.0 g/dl (a hemoglobin less than 10.0 g/dL is acceptable if it is corrected by erythropoietin or transfusion) * Platelet count greater than or equal to 100 x 10\^9 /L 8. Adequately maintained liver function * Total bilirubin: less than or equal to 1.5 times the upper limits of normal (ULN) and * Alkaline phosphatase(ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 x ULN (in the case of liver metastases less than or equal to 5 x ULN) 9. Adequately maintained renal function * Serum creatinine less than or equal to 2.0 mg/dl or * Calculated creatinine clearance greater than or equal to 40 ml/min (Cockcroft and Gault formula) 10. Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or lower, except for * alopecia * stable sensory neuropathy less than or equal to Grade 2 11. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 12. Life expectancy of greater than or equal to 3 months 13. Patients willing and able to comply with the study protocol for the duration of the study 14. Patients who have provided written consent to participate in this study
Exclusion criteria
1. Patients who have received a chemotherapy, radiation, biologics, immunotherapy or hormonal therapy within three weeks before treatment start (but, palliative radiation can be enrolled) 2. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen 3. Patients with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least four weeks before starting treatment in this study. Any signs and/or symptoms of brain metastases must be stable for at least four weeks before starting study treatment 4. Patients with meningeal carcinomatosis 5. Significant cardiovascular impairment * Myocardial infarction within the past six months, unstable angina, history of congestive heart failure NYHA class III or IV, or serious cardiac arrhythmia * QTc prolongation (Bazett's Formula greater than 480 msec) or congenital long QT syndrome 6. Severe/uncontrolled intercurrent illness/infection required administration of antibiotic injection 7. Patients who have processed a major surgery within four weeks before participation in this clinical trial 8. Patients who have had a prior malignancy within the past five years other than breast cancer (but, treated non-melanoma skin cancer and carcinoma in situ of the cervix will not be excluded) 9. Patients with known positive HIV status 10. Patients who have received genetic therapy or other investigational drug within 4 weeks before treatment start or expected to receive prohibited medication 11. Patients with prior allergies to Halichondrin B, its derivatives, active ingredient, or other diluting agent 12. Patients who have received this investigational product before registration for this study 13. Patients who are pregnant, who may possibly be pregnant, or are lactating 14. Patients who do not agree to practice contraception for the study periods 15. Patients who have participated in other clinical trial within 4 weeks before screening 16. Patients otherwise judged by investigator or sub investigator to be unsuitable for inclusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Treatment-emergent Serious Adverse Event (SAE) | mean of 3.76 months | An AE is defined as any harmful, untoward sign (including abnormal laboratory value, etc.), symptom, or disease in a participant administered investigational product that does not necessarily have a causal relationship with treatment. An SAE is defined as an AE that is life threatening or results in death, results in hospitalization (initial or prolonged), results in a disability (significant, persistent, or permanent change, impairment, damage or disruption in the participant's body function/structure, physical activities, or quality of life), results in a congenital anomaly, or requires intervention to prevent permanent impairment or damage. TEAEs are defined as those events that started on or after the date and time of administration of the first dose of study drug and those events that were present prior to the administration of the first dose of study drug and increased in severity during the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | mean of 3.76 months | DCR is defined as the number of participants with complete response (CR), partial response (PR), and stable disease (SD). The Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to assess the tumor response. Tumor response was evaluated by investigators. CR is defined as the disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to \<10 millimeters (mm) in the short axis. PR is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (SLD increased by at least 20% from the smallest value on study \[including baseline, if that is the smallest\]. The SLD must also demonstrate an absolute increase of at least 5 mm. \[Two lesions increasing from 2 mm to 3 mm, for example, does not qualify\]). |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Eribulin Mesylate 1.4 mg/m^2 Participants received 1.4 milligrams per meters squared (mg/m\^2) eribulin mesylate intravenously over the course of 2 to 5 minutes on Day 1 and Day 8 of each 21-day cycle. | 101 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Aggravation of Steral Pain | 1 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Poor Tolerance | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | Eribulin Mesylate 1.4 mg/m^2 |
|---|---|
| Age, Continuous | 50.36 Years STANDARD_DEVIATION 10.71 |
| Sex: Female, Male Female | 101 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 101 / 101 |
| serious Total, serious adverse events | 20 / 101 |
Outcome results
Primary
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Treatment-emergent Serious Adverse Event (SAE)
An AE is defined as any harmful, untoward sign (including abnormal laboratory value, etc.), symptom, or disease in a participant administered investigational product that does not necessarily have a causal relationship with treatment. An SAE is defined as an AE that is life threatening or results in death, results in hospitalization (initial or prolonged), results in a disability (significant, persistent, or permanent change, impairment, damage or disruption in the participant's body function/structure, physical activities, or quality of life), results in a congenital anomaly, or requires intervention to prevent permanent impairment or damage. TEAEs are defined as those events that started on or after the date and time of administration of the first dose of study drug and those events that were present prior to the administration of the first dose of study drug and increased in severity during the study.
Time frame: mean of 3.76 months
Population: Safety Set: all participants who are administered investigational product at least once for the analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eribulin Mesylate 1.4 mg/m^2 | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Treatment-emergent Serious Adverse Event (SAE) | TEAE | 101 Participants |
| Eribulin Mesylate 1.4 mg/m^2 | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Treatment-emergent Serious Adverse Event (SAE) | Treatment-emergent SAE | 20 Participants |
Secondary
Disease Control Rate (DCR)
DCR is defined as the number of participants with complete response (CR), partial response (PR), and stable disease (SD). The Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to assess the tumor response. Tumor response was evaluated by investigators. CR is defined as the disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to \<10 millimeters (mm) in the short axis. PR is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (SLD increased by at least 20% from the smallest value on study \[including baseline, if that is the smallest\]. The SLD must also demonstrate an absolute increase of at least 5 mm. \[Two lesions increasing from 2 mm to 3 mm, for example, does not qualify\]).
Time frame: mean of 3.76 months
Population: Full Analysis Set: participants who were administered investigational product at least once after enrollment and had at least one primary efficacy data value since Baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eribulin Mesylate 1.4 mg/m^2 | Disease Control Rate (DCR) | CR | 1 Participants |
| Eribulin Mesylate 1.4 mg/m^2 | Disease Control Rate (DCR) | PR | 15 Participants |
| Eribulin Mesylate 1.4 mg/m^2 | Disease Control Rate (DCR) | SD | 33 Participants |