Phase I/II Study of Neoadjuvant Carboplatin, Eribulin Mesylate and Trastuzumab (ECH) for Operable HER2 Positive Breast Cancer
Overview
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Vector Oncology
- Enrollment
- 12
- Locations
- 4
- Primary Endpoint
- Pathologic Response
Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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
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
Arms & Interventions
Eribulin, carboplatin, and trastuzumab
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: eribulin (Drug)
Eribulin, carboplatin, and trastuzumab
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: carboplatin (Drug)
Eribulin, carboplatin, and trastuzumab
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: trastuzumab (Drug)
Outcomes
Primary Outcomes
Pathologic Response
Time Frame: Assessed at time of definitive surgery, approximately 21-26 weeks from study treatment start
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 Outcomes
- Clinical Response(Assessed prior to definitive surgery, approximately 18 weeks from study treatment start.)