Carboplatin and Eribulin Mesylate in Triple Negative Breast Cancer Patients

Phase II Neoadjuvant Trial With Carboplatin and Eribulin Mesylate in Triple Negative Breast Cancer Patients

This phase II trial studies how well giving eribulin mesylate and carboplatin together before surgery works in treating patients with stage I-III triple-negative breast cancer. Drugs used in chemotherapy, such as eribulin mesylate and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Study Overview

• Status: Unknown
• Conditions: Male Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Triple-negative Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIIC Breast Cancer; Estrogen Receptor-negative Breast Cancer; Progesterone Receptor-negative Breast Cancer; HER2-negative Breast Cancer
• Intervention / Treatment: Drug: carboplatin; Drug: eribulin mesylate; Procedure: biopsy

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the pathologic complete response rate (pCR) at the time of definitive surgery.

SECONDARY OBJECTIVES:

I. Determination of the clinical response rate, as measured by clinical exam and imaging studies prior to initiation of therapy and prior to surgery.

II. Measurement of alpha B-crystalline in tissue obtained before initiation of therapy and at the time of definitive surgery.

III. Stem cell markers (cluster of differentiation [CD]44+, CD24-, CD133, aldehyde dehydrogenase 1 [ALDH1] and evaluation of the NOTCH pathway) in tissue obtained before initiation of therapy and at the time of definitive surgery.

IV. Measurement of proliferation markers (Ki67) before and after treatment in tissue obtained before imitation of therapy and at the time of definitive surgery.

V. Measurement of beta III tubulin in tissue obtained before initiation of therapy and at the time of definitive surgery.

VI. Measurement of Tau in tissue obtained before initiation of therapy and at the time of definitive surgery.

VII. Safety evaluation, including following of patients for alopecia and neuropathy.

VIII. Epidermal growth factor receptor (EGFR) staining before and after treatment in tissue obtained before initiation of therapy and at the time of definitive surgery.

OUTLINE:

Patients receive eribulin mesylate intravenously (IV) over 2-5 minutes and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologically confirmed breast cancer; diagnosis must be reviewed and confirmed by the pathology department at Northwestern Memorial Hospital prior to registration on study, and all biopsy materials need to be reviewed and available for correlative studies
• Patients must have stage I-III breast cancer
• Patients must have estrogen receptor-negative (ER-), progesterone receptor-negative (PR-), human epidermal growth factor receptor 2-negative (Her2-) (0, 1+) or fluorescent in situ hybridization (FISH) < ratio of 1.8
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) by mammogram, ultrasound or physical exam
• Prior diagnosis of cancer is allowed as long as patient is free of disease and has been off treatment for the prior malignancy for a minimal interval of one year
• Patients must have a life expectancy of > 12 weeks
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 80%)
• Leukocytes >= 3,000/ul
• Absolute neutrophil count >= 1,500/ul
• Platelets >= 100,000/ul
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/ alanine transaminase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
• Creatinine: within normal institutional limits
• OR creatinine clearance >= 60 mL/min/1.73^2 for patients with creatinine levels above institutional normal
• Women of childbearing potential must commit to the use of effective contraception while on study
• Eligibility of patients receiving medications of substances known to affect, or with the potential to affect, the activity or pharmacokinetics of eribulin will be determined following review of their use by the Principal Investigator
• All patients must have given signed, informed consent prior to registration on study

Exclusion Criteria:

• Prior chemotherapy, immunotherapy or hormonal therapy for breast cancer is NOT allowed
• Concomitant radiotherapy is NOT allowed
• Patients may NOT be receiving any other investigational agents or concurrent anticancer therapies; in addition, use of any herbal (alternative) medicines is NOT permitted
• Patients with uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations what would limit compliance with study requirements are NOT eligible to participate
• Women who are pregnant or lactating are NOT eligible to participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (neoadjuvant chemotherapy); Patients receive eribulin mesylate IV over 2-5 minutes and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Drug: carboplatin; Given IV; Other Names: Carboplat; CBDCA; JM-8; Paraplatin; Paraplat; Drug: eribulin mesylate; Given IV; Other Names: Halaven; E7389; ER-086526; B1939; halichrondrin B analog; Procedure: biopsy; Correlative studies; Other Names: biopsies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the pathologic complete response rate (pCR).	Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy)

Secondary Outcome Measures

Outcome Measure	Time Frame
Measurement of alpha B-crystalline in tissue obtained	Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy)
Stem cell markers (CD44+, CD24-, CD133, ALDH1 and evaluation of the NOTCH pathway) in tissue	Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy)
Measurement of proliferation markers (Ki67)	Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy)
Measurement of beta III tubulin in tissue	Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy)
Measurement of Tau in tissue	Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy)
Determination of the clinical response rate, as measured by clinical exam and imaging studies prior to initiation of therapy and prior to surgery.	Imaging studies at baseline and at time of surgery (after approximately 12 weeks of neoadjuvant therapy)
Safety profile of this drug combination	Symptom assessment prior to each cycle (approximately every 3 weeks) and until resolution 6 months after the last dose of study treatment
EGFR staining before and after treatment	Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy)

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: Eisai Inc.
• Investigators: Principal Investigator: Virginia Kaklamani, MD, Northwestern University

Publications and helpful links

General Publications

• Kaklamani VG, Jeruss JS, Hughes E, Siziopikou K, Timms KM, Gutin A, Abkevich V, Sangale Z, Solimeno C, Brown KL, Jones J, Hartman AR, Meservey C, Jovanovic B, Helenowski I, Khan SA, Bethke K, Hansen N, Uthe R, Giordano S, Rosen S, Hoskins K, Von Roenn J, Jain S, Parini V, Gradishar W. Phase II neoadjuvant clinical trial of carboplatin and eribulin in women with triple negative early-stage breast cancer (NCT01372579). Breast Cancer Res Treat. 2015 Jun;151(3):629-38. doi: 10.1007/s10549-015-3435-y. Epub 2015 May 26.

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Anticipated): June 1, 2020
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: June 1, 2011
• First Submitted That Met QC Criteria: June 10, 2011
• First Posted (Estimate): June 14, 2011

Study Record Updates

• Last Update Posted (Actual): June 7, 2019
• Last Update Submitted That Met QC Criteria: June 6, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Breast Neoplasms, Male; Antineoplastic Agents; Carboplatin
• Other Study ID Numbers: NU 10B07; NCI-2011-00600 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); STU00045038 (Other Identifier: Northwestern University IRB#)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No