Brain Metastases, Metastatic Breast Cancer
Conditions
Keywords
eribulin, central nervous system, CNS, Eribulin Mesylate, Halaven
Brief summary
Subjects are asked to take part in a clinical research study that tests Eribulin, a new drug. Eribulin is an investigational (experimental) anti-cancer agent that has not been approved by the Food and Drug Administration (FDA) for use in patients with brain metastases. Eribulin is FDA approved for use in patients with metastatic breast cancer but the effect it may or may not have on brain metastases has not been studied.
Detailed description
Primary Objectives: To determine the 3-month central nervous system (CNS)-progression free survival (PFS) for patients with metastatic breast cancer with brain metastases treated with eribulin mesylate. Secondary Objective(s): 1\. Estimate CNS complete and partial response rates (CR and PR) and duration of CNS response in this patient population. 2 Evaluate toxicity in patients with breast cancer with brain metastases treated with eribulin mesylate. 3 Estimate clinical benefit rate (CBR) at 3 months in breast cancer patients with brain metastases treated with eribulin mesylate. (CBR is the sum of CR, PR and stable disease at 3 months). 4 To estimate systemic disease (extra cranial) response rate and duration of systemic response in this patient population. 5 Overall survival in this patient population. Design: This is a phase II study that will require patients to evaluate the primary objective (CNS PFS at 3 months). Study patients will have a baseline brain MRI and a second MRI at 12 weeks to evaluate disease.
Interventions
DRUGEribulin Mesylate
Most subjects will begin eribulin mesylate at 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.
DEVICEMRI
An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate
DRUGPre-Medication: Zofran
Zofran at 8mg orally. Given at the discretion of the treating physician
DRUGPre-Medication: Decadron
decadron at 8mg orally. Given at the discretion of the treating physician
Sponsors
Case Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female with histologically confirmed breast cancer. * Patients must have evidence of metastatic disease (non measurable disease is eligible). * Radiologically confirmed metastatic brain lesion by MRI. * Brain metastases from breast cancer with or without prior WBRT, STS of surgical resection. Progression must be documented in an at least one lesion untreated by SRS or in any site after surgery or WBRT. * Patients must be neurologically stable and with stable dose steroids and anticonvulsants for at least 1 week prior to obtaining the baseline MRI of the brain, and/or at least 1 week prior to beginning study treatment. * No presence of uncontrolled systemic disease or tumor related complication which, in opinion of the investigator, might restrict life expectancy to less than 3 months. * Patients may not be on any cytotoxic chemotherapy or hormonal treatment for breast cancer during protocol treatment. Trastuzumab is allowed in HER2 positive patients). * Able to comprehend and willing to sign an Informed Consent Form (ICF) * Karnofsky performance status ≥ 60 * No brain radiation therapy \> 4 weeks * No chemotherapy for \> 3 weeks before planned start of protocol treatment * Adequate bone marrow, renal, and hepatic function, per local reference laboratory ranges as follows: * Absolute neutrophil count (ANC) ≥ 1,500/mm3 * Platelet count ≥ 100,000/mm3 * Hemoglobin ≥ 9 g/dL * Calculated creatinine clearance (CrCl) ≥ 30mL/min (Cockcroft-Gault method) * Patients with normal, mild or moderate hepatic dysfunction are eligible. * Calcium \<10.1 mg/dL (corrected to serum albumin as follows: Corrected Calcium = (0.8 x (4 - patient albumin)) + serum Ca * Females of child-bearing potential must have a negative pregnancy test at screening and agree to take appropriate precautions to avoid pregnancy (double barrier method of birth control or abstinence) from screening through 3 months after the last dose of treatment * Able to undergo MRI evaluation with and without gadolinium contrast
Exclusion criteria
* Patients with the presence of an active infection, abscess or fistula * Known leptomeningeal disease or CNS midline shifts. * Any evidence of severe or uncontrolled systemic disease such as clinically significant cardiovascular, pulmonary, hepatic, renal or metabolic disease. * Severe conduction abnormality including significant QTc prolongation \>450ms. * Patients with grade 3/4 peripheral neuropathy. * Patients with pacemaker or an ICD devices. * Previous treatment with eribulin mesylate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With Central Nervous System (CNS) Progression Free Survival (PFS) | At 12 weeks | The study team will assess the percent of participants without CNS progression at 3 months. The study team will generate a Kaplan- Meier curve of CNS PFS and estimate the PFS and 95% confidence interval (CI) of the PFS. Response and progression by MR were evaluated using WHO/modified McDonald's criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Duration of CNS Response | up to 2 years from start of treatment | The study team will calculate the duration of CNS response. Response and progression by MR were evaluated using WHO/modified McDonald's criteria. |
| Number of Patients Treated With Eribulin Who Experienced Serious Adverse Events | up to 2 years from start of treatment | The study team will evaluate rates (and 95% CI) of toxicity in patients treated with eribulin. |
| Objective Response Rate (RR) | up to 2 years from start of treatment | The study team will calculate the percent of participants with complete and partial response. Response and progression by MR were evaluated using WHO/modified McDonald's criteria. |
| Systemic Disease Response Rate | up to 2 years from start of treatment | The study team will estimate systemic disease response rate (and 95% CI) and perform a Kaplan-Meier analysis for systemic response in this patient population |
| Median Overall Survival (OS) | up to 2 years from start of treatment | The study team will generate a Kaplan-Meier curve of OS. |
| Number of Patients With CBR | At 12 weeks | The study team will sum the proportion of the patients with complete response, partial response and stable disease at 12 weeks (CBR) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Eribulin Mesylate The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate
Eribulin Mesylate: Most subjects will begin eribulin mesylate at 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.
MRI: An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate
Pre-Medication: Zofran: Zofran at 8mg orally. Given at the discretion of the treating physician
Pre-Medication: Decadron: decadron at 8mg orally. Given at the discretion of the treating physician | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Eribulin Mesylate |
|---|---|
| Age, Customized years 20-29 | 0 Participants |
| Age, Customized years 30-39 | 3 Participants |
| Age, Customized years 40-49 | 0 Participants |
| Age, Customized years 50-59 | 3 Participants |
| Age, Customized years 60-69 | 1 Participants |
| Age, Customized years 70-79 | 1 Participants |
| Age, Customized years 80-89 | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 9 |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 3 / 9 |
Outcome results
Primary
Percent of Participants With Central Nervous System (CNS) Progression Free Survival (PFS)
The study team will assess the percent of participants without CNS progression at 3 months. The study team will generate a Kaplan- Meier curve of CNS PFS and estimate the PFS and 95% confidence interval (CI) of the PFS. Response and progression by MR were evaluated using WHO/modified McDonald's criteria.
Time frame: At 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eribulin Mesylate | Percent of Participants With Central Nervous System (CNS) Progression Free Survival (PFS) | 88.9 percentage of participants |
Secondary
Median Duration of CNS Response
The study team will calculate the duration of CNS response. Response and progression by MR were evaluated using WHO/modified McDonald's criteria.
Time frame: up to 2 years from start of treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eribulin Mesylate | Median Duration of CNS Response | 22.6 weeks |
Secondary
Median Overall Survival (OS)
The study team will generate a Kaplan-Meier curve of OS.
Time frame: up to 2 years from start of treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eribulin Mesylate | Median Overall Survival (OS) | 15.7 months |
Secondary
Number of Patients Treated With Eribulin Who Experienced Serious Adverse Events
The study team will evaluate rates (and 95% CI) of toxicity in patients treated with eribulin.
Time frame: up to 2 years from start of treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eribulin Mesylate | Number of Patients Treated With Eribulin Who Experienced Serious Adverse Events | 3 Participants |
Secondary
Number of Patients With CBR
The study team will sum the proportion of the patients with complete response, partial response and stable disease at 12 weeks (CBR)
Time frame: At 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eribulin Mesylate | Number of Patients With CBR | 5 Participants |
Secondary
Objective Response Rate (RR)
The study team will calculate the percent of participants with complete and partial response. Response and progression by MR were evaluated using WHO/modified McDonald's criteria.
Time frame: up to 2 years from start of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eribulin Mesylate | Objective Response Rate (RR) | 11.1 percentage of participants |
Secondary
Systemic Disease Response Rate
The study team will estimate systemic disease response rate (and 95% CI) and perform a Kaplan-Meier analysis for systemic response in this patient population
Time frame: up to 2 years from start of treatment
Population: Data not collected due to too few participants on study for a significant length of time