Study of Neoadjuvant Carboplatin, Eribulin and Trastuzumab for Operable HER2 Positive Breast Cancer - Full Text View

Purpose

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.

Condition	Intervention	Phase
HER-2 Positive Breast Cancer	Drug: eribulin Drug: carboplatin Drug: trastuzumab	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I/II Study of Neoadjuvant Carboplatin, Eribulin Mesylate and Trastuzumab (ECH) for Operable HER2 Positive Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Carboplatin Trastuzumab Eribulin Eribulin mesylate

U.S. FDA Resources

Further study details as provided by ACORN Research, LLC:

Primary Outcome Measures:

Efficacy as measured by pathologic complete response at surgery [ Time Frame: Assessed at time of definitive surgery, 3 to 8 weeks after completion of study treatment ] [ Designated as safety issue: No ]
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, partial pathologic response, or no response.

Secondary Outcome Measures:

Efficacy as measured by clinical response prior to surgery [ Time Frame: Assessed prior to definitive surgery, 3 weeks after completion of study treatment ] [ Designated as safety issue: No ]
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, partial response, no response, and progression.
Toxicity with a focus on peripheral neuropathy and cardiac toxicity [ Time Frame: Continuously from start of study treatment (Cycle 1 Day 1) until 48 weeks after completion of study treatment ] [ Designated as safety issue: Yes ]
Toxicity will be assessed continuously during study participation through the reporting of adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Estimated Enrollment:	56
Study Start Date:	August 2011
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 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.	Drug: 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. Other Names: eribulin mesylate HALAVEN Drug: carboplatin Carboplatin area under the curve (AUC) 6 will be administered IV over 15 to 30 minutes on Day 1 of each cycle. Drug: trastuzumab 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. Other Name: Herceptin

Arms

Assigned Interventions

Experimental: 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.

Drug: 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.

Other Names:

eribulin mesylate
HALAVEN

Drug: carboplatin

Carboplatin area under the curve (AUC) 6 will be administered IV over 15 to 30 minutes on Day 1 of each cycle.

Drug: trastuzumab

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.

Other Name: Herceptin

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01388647

Contacts

Contact: Rita LeDoux, RN, BSN, CCRP	(901) 259-8284	rledoux@acorncro.com
Contact: Kellee Rivera	(901) 259-1994	krivera@acorncro.com

Locations

United States, Florida
Holy Cross Hospital	Recruiting
Fort Lauderdale, Florida, United States, 33308
Principal Investigator: Zdenka Segota, MD
United States, Georgia
Northeast Georgia Cancer Care	Recruiting
Athens, Georgia, United States, 30607
Principal Investigator: Petros Nikolinakos, MD
Northwest Georgia Oncology Centers	Recruiting
Marietta, Georgia, United States, 30060
Principal Investigator: Robert Hermann, MD
United States, Tennessee
The West Clinic	Recruiting
Memphis, Tennessee, United States, 38120
Principal Investigator: Kurt Tauer, MD

Sponsors and Collaborators

ACORN Research, LLC

Eisai Inc.

Investigators

Study Chair:

Lee Schwartzberg, MD, FACP

ACORN Research, LLC and The West Clinic

More Information

No publications provided

Responsible Party:	ACORN Research, LLC
ClinicalTrials.gov Identifier:	NCT01388647 History of Changes
Other Study ID Numbers:	ACORN ALSSNBC1006
Study First Received:	July 5, 2011
Last Updated:	February 1, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by ACORN Research, LLC:

Neoadjuvant Treatment
HER-2 Positive Breast Cancer

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

Trastuzumab
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013