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

This study has been terminated.
(Closed early due to increased hematologic toxicity and possible reduced efficacy)
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Vector Oncology
ClinicalTrials.gov Identifier:
NCT01388647
First received: July 5, 2011
Last updated: July 30, 2015
Last verified: December 2014
  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:


Further study details as provided by Vector Oncology:

Primary Outcome Measures:
  • Pathologic Response [ Time Frame: Assessed at time of definitive surgery, approximately 21-26 weeks from study treatment start ] [ 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 (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 [ Time Frame: Assessed prior to definitive surgery, approximately 18 weeks from study treatment start. ] [ 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 (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.


Other Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Eribulin in Combination With Carboplatin and Trastuzuamb [ Time Frame: Approximately 22 days from study treatment start, per subject ] [ Designated as safety issue: Yes ]
    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.

  • Dose Limiting Toxicity (DLT) [ Time Frame: Approximately 22 days from study treatment start, per subject ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 12
Study Start Date: August 2011
Study Completion Date: September 2014
Primary Completion Date: June 2014 (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

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Florida
Holy Cross Hospital
Fort Lauderdale, Florida, United States, 33308
United States, Georgia
Northeast Georgia Cancer Care
Athens, Georgia, United States, 30607
Northwest Georgia Oncology Centers
Marietta, Georgia, United States, 30060
United States, Tennessee
The West Clinic
Memphis, Tennessee, United States, 38120
Sponsors and Collaborators
Vector Oncology
Eisai Inc.
Investigators
Study Chair: Lee Schwartzberg, MD, FACP Vector Oncology and The West Clinic
  More Information

Responsible Party: Vector Oncology
ClinicalTrials.gov Identifier: NCT01388647     History of Changes
Other Study ID Numbers: ALSSNBC1006 
Study First Received: July 5, 2011
Results First Received: May 28, 2015
Last Updated: July 30, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Vector Oncology:
Neoadjuvant Treatment
HER-2 Positive Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carboplatin
Trastuzumab
Antineoplastic Agents

ClinicalTrials.gov processed this record on December 02, 2016