A Pilot Study of Eribulin in Breast Cancer (BC) Patients With Brain Metastases Previously Treated With Anthracyclines and Taxanes

This is a pilot study, the principal investigator plans to enroll 14 patients. If 2 or more responses are documented, the principal investigator will consider to start a new phase II study. If there is less than 2 responses in the 14 patients, it is unlikely that Eribulin will produce 15% or more response rate in patients with active brain metastases, thus indicating no need to study further. Based on Poisson distribution, there is 38% probability of observing 1 or 0 response even if the underlying response is 15%. There is no null hypothesis, hence no p-value of significance.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Eribulin Mesylate

• Study Type: Interventional
• Enrollment (Anticipated): 14
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Elaine Tabanguil; Phone Number: +6568802216; Email: Elaine_E_TABANGUIL@ttsh.com.sg
• Study Contact Backup: Name: Xiaoying Xu; Email: Xiaoying_XU@ttsh.com.sg

Study Locations

• Singapore
  • Singapore, Singapore, 308433
    • Recruiting
    • Tan Tock Seng Hospital
    • Contact: Elaine Tabanguil; Phone Number: +6568802216; Email: Elaine_E_TABANGUIL@ttsh.com.sg
• Taiwan
  • Taoyuan city, Taiwan, 333
    • Recruiting
    • Chang-Gung Memorial Hospital
    • Contact: Wen-Chi Shen; Phone Number: 2517 +88633281200; Email: c220273@cgmh.org.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Female patients with histologically or cytologically confirmed carcinoma of the breast.
2. Patients with locally advanced or metastatic disease who have received an anthracycline (e.g. doxorubicin, epirubicin) and a taxane (e.g. paclitaxel, docetaxel), either in combination or in separate regimens. It can be used in neo-adjuvant, adjuvant or metastatic setting.
3. Patients must have measurable brain metastases (minimum size of 10mm in long axis) which is asymptomatic and does not required any treatment or had failed to respond or progress after either radiation treatment or stereotactic radiosurgery.
4. Patients who are deemed to have asymptomatic brain metastases should not be on systemic corticosteroid at enrolment. Patients who have brain metastases that have failed previous radiation therapy or stereotactic radiosurgery are allowed to be on systemic corticosteroid at enrolment. Baseline dose of corticosteroid should be documented.
5. Patients with known HER2 positive tumors may additionally have been treated with trastuzumab and/or pertuzumab or trastuzumab emtasine in centers where this treatment is available.
6. Patients with known estrogen and/or progesterone receptor-expressing tumors may have additionally been treated with hormonal therapy
7. Resolution of all previous chemotherapy or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy ≤Grade 2 and alopecia
8. Age above 21 years
9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
10. Life expectancy of more than 3 months
11. Adequate renal function as evidenced by serum creatinine < 1.5 mg/dL or calculated creatinine clearance > 50 mL/minute (min) per the Cockcroft and Gault formula
12. Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) above 1.5 x 109/L, hemoglobin above 10.0 g/dL, and platelet count above 100 x 109/L.
13. Adequate liver function as evidenced by bilirubin less than 1.5 times the upper limits of normal (ULN) and alkaline phosphatase, alanine transaminase (ALT), and aspartate transaminase (AST) less than 3 x ULN (in the case of liver metastases less than 5 x ULN), or in case of bone metastases, liver specific alkaline phosphatase less than 3 x ULN
14. Patient's willing and able to comply with the study protocol for the duration of the study
15. Written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice. However, hormonal therapy must be discontinued one week before administration of study

Exclusion Criteria:

1. Patients who have received chemotherapy, radiation, or biological therapy within two weeks, or hormonal therapy within one week before study treatment start, or any investigational drug within four weeks before study treatment start.
2. Women who are pregnant or breast-feeding; women of childbearing potential with either a positive pregnancy test at screening or no pregnancy test; women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception (considered to be two methods of contraception, one of which must be a barrier method, e.g. condom, diaphragm or cervical cap). Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
3. Severe/uncontrolled intercurrent illness/infection.
4. Significant cardiovascular impairment (history of congestive heart failure > NYHA grade II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia)
5. Patients with known positive HIV status
6. Patients who have had a prior malignancy, other than carcinoma in situ of the cervix, or non-melanoma skin cancer, unless the prior malignancy was diagnosed and definitively treated above 5 years previously with no subsequent evidence of recurrence
7. Patients with neuropathy > Grade 2 at screening.
8. Patients with QTC > 500 msec at screening.
9. Concurrent hormonal therapy for metastatic breast cancer is not allowed. However, Her2 positive metastatic breast cancer patients who progressed on prior anti-Her2 directed therapy may have concurrent eribulin and trastuzumab, but not trastuzumab emtasine.
10. Patient with leptomeningeal only disease, without other measurable brain metastasis, is excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eribulin; Patients enrolled into the study will receive Eribulin 1.4mg/m2 on days 1 and 8 of a 21-day treatment cycle till disease progression or non-tolerable toxicity.	Drug: Eribulin Mesylate; 1.4mg/m2/dose on days 1 and 8 of a 21-day treatment cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Tumor Response Rate in Brain as measured using RANO-BM criteria	To evaluate the tumor response rate in the the brain every 6 weeks for the first 4 cycles of Eribulin, then every 9 weeks for the subsequent cycles.	Every 6 weeks for the first 4 cycles, then every 9 weeks for the subsequent cycles

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extracranial objective tumor response rate as measured using RECIST 1.1 criteria	To evaluate the extracranial objective tumor response by doing CT Scan/MRI every 6 weeks for the first 4 cycles of Eribulin, then every 9 weeks for the subsequent cycles.	Every 6 weeks for the first 4 cycles, then every 9 weeks for the subsequent cycles
Duration of Response in Brain	To assess the duration of response by doing an MRI Brain every 6 weeks for the first 4 cycles of Eribulin, then every 9 weeks for the subsequent cycles. .	Every 6 weeks for the first 4 cycles, then every 9 weeks for the subsequent cycles
Assessment of toxicities such as neuropathy, hematological and hepatological toxicities	To assess the toxicities of patients receiving Eribulin. The assessment will include the physical examinations, weight and vital signs monitoring, 12 lead ECGs, 2D Echo, collection of Adverse Events (AE) as well as Laboratory assessments including hematology and chemistry. Toxicity will be assessed based on the medical review of adverse events, reports and laboratory tests throughout the study.	3 years

Collaborators and Investigators

• Sponsor: Tan Tock Seng Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2017
• Primary Completion (Anticipated): April 30, 2020
• Study Completion (Anticipated): April 30, 2020

Study Registration Dates

• First Submitted: December 19, 2017
• First Submitted That Met QC Criteria: January 25, 2018
• First Posted (Actual): January 29, 2018

Study Record Updates

• Last Update Posted (Actual): February 27, 2018
• Last Update Submitted That Met QC Criteria: February 26, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Breast Neoplasms; Brain Neoplasms
• Other Study ID Numbers: JS16104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No