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

HER-2 Positive Breast Cancer Clinical Trial

Official title:

Phase I/II Study of Neoadjuvant Carboplatin, Eribulin Mesylate and Trastuzumab (ECH) for Operable HER2 Positive Breast Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01388647
• Other study ID #: ALSSNBC1006
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: July 5, 2011
• Last updated: July 30, 2015
• Start date: August 2011
• Est. completion date: September 2014

Study information

• Verified date: December 2014
• Source: Vector Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: September 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• HER-2 Positive Breast Cancer

Intervention

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

Locations

Country	Name	City	State
United States	Northeast Georgia Cancer Care	Athens	Georgia
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Northwest Georgia Oncology Centers	Marietta	Georgia
United States	The West Clinic	Memphis	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vector Oncology	Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Maximum Tolerated Dose (MTD) of Eribulin in Combination With Carboplatin and Trastuzuamb	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.	Approximately 22 days from study treatment start, per subject	Yes
Other	Dose Limiting Toxicity (DLT)	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.	Approximately 22 days from study treatment start, per subject	Yes
Primary	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	No
Secondary	Clinical Response	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.	Assessed prior to definitive surgery, approximately 18 weeks from study treatment start.	No