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Study of Neoadjuvant Carboplatin, Eribulin and Trastuzumab for Operable HER2 Positive Breast Cancer

Primary Purpose

HER-2 Positive Breast Cancer

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
eribulin
carboplatin
trastuzumab
Sponsored by
Vector Oncology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HER-2 Positive Breast Cancer focused on measuring Neoadjuvant Treatment, HER-2 Positive Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Written informed consent
  • Females; 18 years of age or greater
  • Histologically proven invasive breast cancer
  • American Joint Committee on Cancer (AJCC) clinical stage IIA - IIIB
  • Tumor size greater than 10 millimeters
  • HER2 positive
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Estrogen receptor (ER) positive or negative
  • Ejection fraction greater than or equal to lower limit of normal for the institution by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA)
  • Less than or equal to Grade 1 neuropathy according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
  • Planned lumpectomy or mastectomy
  • Eligible for radiation therapy
  • No prior treatment for invasive breast cancer
  • Adequate organ system function per protocol as determined within 7 days prior to first dose of study treatment
  • Women of childbearing potential must have a negative pregnancy test within 7 days prior to the first dose of study treatment and must agree to use adequate contraception methods during study treatment and for a minimum of 6 months following trastuzumab discontinuation
  • Female subjects who are lactating should discontinue nursing prior to the first dose of study treatment and should refrain from nursing throughout the treatment period

Exclusion Criteria:

  • Fine needle cytology only without other histologic evidence of invasive breast cancer
  • Inflammatory breast cancer
  • AJCC clinical stage T1a-b breast cancer (primary tumor less than or equal to 10 millimeters)
  • Evidence of metastatic disease
  • HER2 negative
  • Ejection fraction less than lower limit of normal for the institution by ECHO or MUGA
  • Corrected QT interval greater than 480 milliseconds
  • Pre-existing cardiac dysfunction
  • Prior history of invasive cancer within the past 3 years
  • Synchronous bilateral breast cancer
  • Pre-existing CTCAE v4.0 Grade 2 or greater neuropathy
  • Hypersensitivity to halichondrin B or halichondrin B chemical derivative
  • History of severe allergic reactions to cisplatin or other platinum containing compounds, or mannitol
  • Mild, moderate, or severe hepatic impairment
  • Moderate or severe renal impairment
  • Hypokalemia or hypomagnesemia if it cannot be corrected prior to the first dose of study treatment
  • Organ allografts requiring immunosuppression
  • Known positive human immunodeficiency virus (HIV) status
  • Prior major surgery within 28 days prior to the first dose of study treatment and/or presence of any non-healing wound, fracture, or ulcer
  • Minor surgery or radiation therapy within 14 days prior to the first dose of study treatment
  • Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures

Sites / Locations

  • Holy Cross Hospital
  • Northeast Georgia Cancer Care
  • Northwest Georgia Oncology Centers
  • The West Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Eribulin, carboplatin, and trastuzumab

Arm Description

During Phase I, the eribulin dose will be assigned upon study enrollment. The maximum tolerated dose (MTD) determined in Phase I will be the dose used for Phase II. Eribulin will be administered intravenously (IV) over 2 to 5 minutes on Days 1 and 8 of each cycle. Carboplatin area under the curve (AUC) 6 will be administered IV over 15 to 30 minutes on Day 1 of each cycle. Trastuzumab will be administered as an IV infusion on Day 1 of each cycle. A loading dose of 8 mg/kg of trastuzumab will be administered over 90 minutes on Cycle 1 Day 1. Then, a maintenance dose of 6 mg/kg of trastuzumab will be administered over 30 to 90 minutes on Day 1 of Cycles 2 - 6.

Outcomes

Primary Outcome Measures

Pathologic Response
Definitive surgery will be performed 3 to 8 weeks after completion of study treatment. The pathology report will be scored for pathologic response: complete pathologic response (no invasive cancer in breast or lymph nodes; residual DCIS or LCIS is acceptable), partial pathologic response (residual invasive cancer in breast and/or lymph nodes), or no response (pathologic staging is equal to or worse than pretreatment clinical staging).

Secondary Outcome Measures

Clinical Response
Clinical assessment of response will be performed 3 weeks after completion of study treatment. The treating physician will assess clinical response using physical examination and radiologic evaluation. Clinical response options are complete response (no invasive tumor in breast and lymph nodes), partial response (> 50% reduction in longest diameter of pretreatment tumor), no response (< 50% response to 10% growth of tumor as determined by longest diameter of pretreatment tumor size), and progression.

Full Information

First Posted
July 5, 2011
Last Updated
July 30, 2015
Sponsor
Vector Oncology
Collaborators
Eisai Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01388647
Brief Title
Study of Neoadjuvant Carboplatin, Eribulin and Trastuzumab for Operable HER2 Positive Breast Cancer
Official Title
Phase I/II Study of Neoadjuvant Carboplatin, Eribulin Mesylate and Trastuzumab (ECH) for Operable HER2 Positive Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
December 2014
Overall Recruitment Status
Terminated
Why Stopped
Closed early due to increased hematologic toxicity and possible reduced efficacy
Study Start Date
August 2011 (undefined)
Primary Completion Date
June 2014 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vector Oncology
Collaborators
Eisai Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study will evaluate the safety and efficacy of eribulin in combination with carboplatin and trastuzumab in the neoadjuvant setting in subjects who are human epidermal growth factor receptor (HER)2 positive and are clinically stage IIA to IIIB. The study regimen will be administered every 3 weeks for a total of 6 cycles followed by definitive surgery.
Detailed Description
During Phase I, the eribulin dose will be assigned upon study enrollment. The maximum tolerated dose (MTD) determined in Phase I will be the dose used for Phase II. Eribulin will be administered intravenously (IV) over 2 to 5 minutes on Days 1 and 8 of each cycle. Carboplatin area under the curve (AUC) 6 will be administered IV over 15 to 30 minutes on Day 1 of each cycle. Trastuzumab will be administered as an IV infusion on Day 1 of each cycle. A loading dose of 8 mg/kg of trastuzumab will be administered over 90 minutes on Cycle 1 Day 1. Then, a maintenance dose of 6 mg/kg of trastuzumab will be administered over 30 to 90 minutes on Day 1 of Cycles 2 - 6. eribulin: During Phase I, the eribulin dose will be assigned upon study enrollment. The maximum tolerated dose (MTD) determined in Phase I will be the dose used for Phase II. Eribulin will be administered intravenously (IV) over 2 to 5 minutes on Days 1 and 8 of each cycle. carboplatin: Carboplatin area under the curve

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HER-2 Positive Breast Cancer
Keywords
Neoadjuvant Treatment, HER-2 Positive Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Eribulin, carboplatin, and trastuzumab
Arm Type
Experimental
Arm Description
During Phase I, the eribulin dose will be assigned upon study enrollment. The maximum tolerated dose (MTD) determined in Phase I will be the dose used for Phase II. Eribulin will be administered intravenously (IV) over 2 to 5 minutes on Days 1 and 8 of each cycle. Carboplatin area under the curve (AUC) 6 will be administered IV over 15 to 30 minutes on Day 1 of each cycle. Trastuzumab will be administered as an IV infusion on Day 1 of each cycle. A loading dose of 8 mg/kg of trastuzumab will be administered over 90 minutes on Cycle 1 Day 1. Then, a maintenance dose of 6 mg/kg of trastuzumab will be administered over 30 to 90 minutes on Day 1 of Cycles 2 - 6.
Intervention Type
Drug
Intervention Name(s)
eribulin
Other Intervention Name(s)
eribulin mesylate, HALAVEN
Intervention Description
During Phase I, the eribulin dose will be assigned upon study enrollment. The maximum tolerated dose (MTD) determined in Phase I will be the dose used for Phase II. Eribulin will be administered intravenously (IV) over 2 to 5 minutes on Days 1 and 8 of each cycle.
Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Description
Carboplatin area under the curve (AUC) 6 will be administered IV over 15 to 30 minutes on Day 1 of each cycle.
Intervention Type
Drug
Intervention Name(s)
trastuzumab
Other Intervention Name(s)
Herceptin
Intervention Description
Trastuzumab will be administered as an IV infusion on Day 1 of each cycle. A loading dose of 8 mg/kg of trastuzumab will be administered over 90 minutes on Cycle 1 Day 1. Then, a maintenance dose of 6 mg/kg of trastuzumab will be administered over 30 to 90 minutes on Day 1 of Cycles 2 - 6.
Primary Outcome Measure Information:
Title
Pathologic Response
Description
Definitive surgery will be performed 3 to 8 weeks after completion of study treatment. The pathology report will be scored for pathologic response: complete pathologic response (no invasive cancer in breast or lymph nodes; residual DCIS or LCIS is acceptable), partial pathologic response (residual invasive cancer in breast and/or lymph nodes), or no response (pathologic staging is equal to or worse than pretreatment clinical staging).
Time Frame
Assessed at time of definitive surgery, approximately 21-26 weeks from study treatment start
Secondary Outcome Measure Information:
Title
Clinical Response
Description
Clinical assessment of response will be performed 3 weeks after completion of study treatment. The treating physician will assess clinical response using physical examination and radiologic evaluation. Clinical response options are complete response (no invasive tumor in breast and lymph nodes), partial response (> 50% reduction in longest diameter of pretreatment tumor), no response (< 50% response to 10% growth of tumor as determined by longest diameter of pretreatment tumor size), and progression.
Time Frame
Assessed prior to definitive surgery, approximately 18 weeks from study treatment start.
Other Pre-specified Outcome Measures:
Title
Maximum Tolerated Dose (MTD) of Eribulin in Combination With Carboplatin and Trastuzuamb
Description
The MTD is defined as the dose at which <= 1 of 6 subjects experience DLT (Dose Limiting Toxicity) and above which >= 2 of 6 subjects experience DLT.
Time Frame
Approximately 22 days from study treatment start, per subject
Title
Dose Limiting Toxicity (DLT)
Description
DLT is defined as grade 4 thrombocytopenia; grade 4 anemia; grade 4 neutropenia lasting > 5 days; or any grade 3 or 4 non-hematologic toxicity occurring during Cycle 1 which is attributable to eribulin, carboplatin, trastuzumab or the combination, or the inability to deliver all three agents at the assigned dose and scheduled time during Cycle 1.The following events are excluded from the DLT definition: grade 3 nausea and/or vomiting responsive to antiemetics; grade 3 fever or infection; grade 3 diarrhea responsive to antidiarrheal therapy.
Time Frame
Approximately 22 days from study treatment start, per subject

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent Females; 18 years of age or greater Histologically proven invasive breast cancer American Joint Committee on Cancer (AJCC) clinical stage IIA - IIIB Tumor size greater than 10 millimeters HER2 positive Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Estrogen receptor (ER) positive or negative Ejection fraction greater than or equal to lower limit of normal for the institution by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) Less than or equal to Grade 1 neuropathy according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 Planned lumpectomy or mastectomy Eligible for radiation therapy No prior treatment for invasive breast cancer Adequate organ system function per protocol as determined within 7 days prior to first dose of study treatment Women of childbearing potential must have a negative pregnancy test within 7 days prior to the first dose of study treatment and must agree to use adequate contraception methods during study treatment and for a minimum of 6 months following trastuzumab discontinuation Female subjects who are lactating should discontinue nursing prior to the first dose of study treatment and should refrain from nursing throughout the treatment period Exclusion Criteria: Fine needle cytology only without other histologic evidence of invasive breast cancer Inflammatory breast cancer AJCC clinical stage T1a-b breast cancer (primary tumor less than or equal to 10 millimeters) Evidence of metastatic disease HER2 negative Ejection fraction less than lower limit of normal for the institution by ECHO or MUGA Corrected QT interval greater than 480 milliseconds Pre-existing cardiac dysfunction Prior history of invasive cancer within the past 3 years Synchronous bilateral breast cancer Pre-existing CTCAE v4.0 Grade 2 or greater neuropathy Hypersensitivity to halichondrin B or halichondrin B chemical derivative History of severe allergic reactions to cisplatin or other platinum containing compounds, or mannitol Mild, moderate, or severe hepatic impairment Moderate or severe renal impairment Hypokalemia or hypomagnesemia if it cannot be corrected prior to the first dose of study treatment Organ allografts requiring immunosuppression Known positive human immunodeficiency virus (HIV) status Prior major surgery within 28 days prior to the first dose of study treatment and/or presence of any non-healing wound, fracture, or ulcer Minor surgery or radiation therapy within 14 days prior to the first dose of study treatment Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lee Schwartzberg, MD, FACP
Organizational Affiliation
Vector Oncology and The West Clinic
Official's Role
Study Chair
Facility Information:
Facility Name
Holy Cross Hospital
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33308
Country
United States
Facility Name
Northeast Georgia Cancer Care
City
Athens
State/Province
Georgia
ZIP/Postal Code
30607
Country
United States
Facility Name
Northwest Georgia Oncology Centers
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
Facility Name
The West Clinic
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38120
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Study of Neoadjuvant Carboplatin, Eribulin and Trastuzumab for Operable HER2 Positive Breast Cancer

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