Clinical trial NCT01388647: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: HER-2 Positive Breast Cancer
Keywords: Neoadjuvant Treatment
HER-2 Positive Breast Cancer
Lead sponsor: Vector Oncology
Sponsor class: OTHER
Collaborators: name: Eisai Inc.
First posted: 2011-07-07
Enrollment: 12
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Pathologic Response
timeFrame: Assessed at time of definitive surgery, approximately 21-26 weeks from study treatment start
Secondary outcomes:
measure: Clinical Response
timeFrame: Assessed prior to definitive surgery, approximately 18 weeks from study treatment start.
Other outcomes:
measure: Maximum Tolerated Dose (MTD) of Eribulin in Combination With Carboplatin and Trastuzuamb
timeFrame: Approximately 22 days from study treatment start, per subject
measure: Dose Limiting Toxicity (DLT)
timeFrame: Approximately 22 days from study treatment start, per subject
Locations:
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Athens
country: United States
facility: Northeast Georgia Cancer Care
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers
state: Georgia
city: Memphis
country: United States
facility: The West Clinic
state: Tennessee
Study officials:
affiliation: Vector Oncology and The West Clinic
name: Lee Schwartzberg, MD, FACP
role: STUDY_CHAIR
References: