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

NCT01388647 | Terminated Phase 1 Results

• 1 other identifier: ALSSNBC1006
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 4

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.

Conditions

HER-2 Positive Breast Cancer

Keywords

Neoadjuvant Treatment; HER-2 Positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic Response

  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).

  Assessed at time of definitive surgery, approximately 21-26 weeks from study treatment start

Secondary Outcomes (1)

• Clinical Response

  Assessed prior to definitive surgery, approximately 18 weeks from study treatment start.

Other Outcomes (2)

• Maximum Tolerated Dose (MTD) of Eribulin in Combination With Carboplatin and Trastuzuamb

  Approximately 22 days from study treatment start, per subject

• Dose Limiting Toxicity (DLT)

  Approximately 22 days from study treatment start, per subject

Study Arms (1)

Eribulin, carboplatin, and trastuzumab

EXPERIMENTAL

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; Drug: carboplatin; Drug: trastuzumab

Interventions

eribulin DRUG

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.

Also known as: eribulin mesylate, HALAVEN

Eribulin, carboplatin, and trastuzumab

carboplatin DRUG

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

Eribulin, carboplatin, and trastuzumab

trastuzumab DRUG

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.

Also known as: Herceptin

Eribulin, carboplatin, and trastuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vector Oncology: lead
• Eisai Inc.: collaborator

Study Sites (4)

Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

Northeast Georgia Cancer Care

Athens, Georgia, 30607, United States

Location

Northwest Georgia Oncology Centers

Marietta, Georgia, 30060, United States

Location

The West Clinic

Memphis, Tennessee, 38120, United States

Location

MeSH Terms

Interventions

eribulin; Carboplatin; Trastuzumab

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Although MTD of eribulin with carboplatin \& trastuzuamb as neoadjuvant therapy was determined by protocol definitions, study closed early due to increased hematologic toxicity \& possible reduced efficacy. Phase II of this trial was not initiated.

Results Point of Contact

• Title: Vice President of Scientific Affairs
• Organization: Vector Oncology

mwalker@vectoroncology.com

901-435-5550

Study Officials

• Lee Schwartzberg, MD, FACP

  Vector Oncology and The West Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2011
• First Posted: July 7, 2011
• Study Start: August 1, 2011
• Primary Completion: June 1, 2014
• Study Completion: September 1, 2014
• Last Updated: August 28, 2015
• Results First Posted: August 28, 2015

Record last verified: 2014-12

Locations

US (4)