Carboplatin and Eribulin Mesylate in Triple Negative Breast Cancer Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Virginia Kaklamani, Northwestern University
ClinicalTrials.gov Identifier:
NCT01372579
First received: June 1, 2011
Last updated: June 3, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
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 Cancer
Drug: eribulin mesylate
Drug: carboplatin
Procedure: biopsy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Neoadjuvant Trial With Carboplatin and Eribulin Mesylate in Triple Negative Breast Cancer Patients

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • To determine the pathologic complete response rate (pCR). [ Time Frame: Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Measurement of alpha B-crystalline in tissue obtained [ Time Frame: Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy) ] [ Designated as safety issue: No ]
  • Stem cell markers (CD44+, CD24-, CD133, ALDH1 and evaluation of the NOTCH pathway) in tissue [ Time Frame: Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy) ] [ Designated as safety issue: No ]
  • Measurement of proliferation markers (Ki67) [ Time Frame: Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy) ] [ Designated as safety issue: No ]
  • Measurement of beta III tubulin in tissue [ Time Frame: Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy) ] [ Designated as safety issue: No ]
  • Measurement of Tau in tissue [ Time Frame: Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy) ] [ Designated as safety issue: No ]
  • Determination of the clinical response rate, as measured by clinical exam and imaging studies prior to initiation of therapy and prior to surgery. [ Time Frame: Imaging studies at baseline and at time of surgery (after approximately 12 weeks of neoadjuvant therapy) ] [ Designated as safety issue: No ]
  • Safety profile of this drug combination [ Time Frame: Symptom assessment prior to each cycle (approximately every 3 weeks) and until resolution 6 months after the last dose of study treatment ] [ Designated as safety issue: Yes ]
  • EGFR staining before and after treatment [ Time Frame: Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy) ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: August 2011
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: eribulin mesylate
Given IV
Other Names:
  • Halaven
  • B1939
  • E7389
  • ER-086526
  • halichrondrin B analog
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Procedure: biopsy
Correlative studies
Other Name: biopsies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01372579

Locations
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Eisai Inc.
Investigators
Principal Investigator: Virginia Kaklamani, MD Northwestern University
  More Information

No publications provided

Responsible Party: Virginia Kaklamani, Virginia Kaklamani, MD, Northwestern University
ClinicalTrials.gov Identifier: NCT01372579     History of Changes
Other Study ID Numbers: NU 10B07, NCI-2011-00600, STU00045038
Study First Received: June 1, 2011
Last Updated: June 3, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014