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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:
ClinicalTrials.gov Identifier:
NCT01388647
First Posted: July 7, 2011
Last Update Posted: August 28, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Vector Oncology
July 5, 2011
July 7, 2011
May 28, 2015
August 28, 2015
August 28, 2015
August 2011
June 2014   (Final data collection date for primary outcome measure)
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).
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 ]
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.
Complete list of historical versions of study NCT01388647 on ClinicalTrials.gov Archive Site
Clinical Response [ Time Frame: Assessed prior to definitive surgery, approximately 18 weeks from study treatment start. ]
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.
  • Efficacy as measured by clinical response prior to surgery [ Time Frame: Assessed prior to definitive surgery, 3 weeks after completion of study treatment ]
    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 ]
    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
  • Maximum Tolerated Dose (MTD) of Eribulin in Combination With Carboplatin and Trastuzuamb [ Time Frame: Approximately 22 days from study treatment start, per subject ]
    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 ]
    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.
Not Provided
 
Study of Neoadjuvant Carboplatin, Eribulin and Trastuzumab for Operable HER2 Positive Breast Cancer
Phase I/II Study of Neoadjuvant Carboplatin, Eribulin Mesylate and Trastuzumab (ECH) for Operable HER2 Positive Breast Cancer

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.

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

Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
HER-2 Positive Breast Cancer
  • 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
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.
Interventions:
  • Drug: eribulin
  • Drug: carboplatin
  • Drug: trastuzumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
12
September 2014
June 2014   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: Female
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01388647
ALSSNBC1006
No
Not Provided
Not Provided
Vector Oncology
Vector Oncology
Eisai Inc.
Study Chair: Lee Schwartzberg, MD, FACP Vector Oncology and The West Clinic
Vector Oncology
December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP