Carboplatin and Eribulin Mesylate in Triple Negative Breast Cancer Patients

Stage IIIA Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01372579
• Other study ID #: NU 10B07
• Secondary ID: NCI-2011-00600ST
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 2011
• Est. completion date: June 2021

Study information

• Verified date: May 2019
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: June 2021
• Est. primary completion date: June 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Breast Neoplasms, Male
• Estrogen Receptor-negative Breast Cancer
• HER2-negative Breast Cancer
• Male Breast Cancer
• Progesterone Receptor-negative Breast Cancer
• Stage IA Breast Cancer
• Stage IB Breast Cancer
• Stage II Breast Cancer
• Stage IIIA Breast Cancer
• Stage IIIB Breast Cancer
• Stage IIIC Breast Cancer
• Triple Negative Breast Neoplasms
• Triple-negative Breast Cancer

Intervention

Drug:
• eribulin mesylate
Given IV
• carboplatin
Given IV

Procedure:
• biopsy
Correlative studies

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	Measurement of proliferation markers (Ki67)		Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy)
Secondary	Measurement of beta III tubulin in tissue		Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy)
Secondary	Measurement of Tau in tissue		Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy)
Secondary	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)
Secondary	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
Secondary	EGFR staining before and after treatment		Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy)