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Carboplatin and Eribulin Mesylate in Triple Negative Breast Cancer Patients

Primary Purpose

Estrogen Receptor-negative Breast Cancer, HER2-negative Breast Cancer, Male Breast Cancer

Status

Unknown status

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

eribulin mesylate

carboplatin

biopsy

About this trial

This is an interventional treatment trial for Estrogen Receptor-negative Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Northwestern University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (neoadjuvant chemotherapy)

Arm Description

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.

Outcomes

Primary Outcome Measures

To determine the pathologic complete response rate (pCR).

Secondary Outcome Measures

Measurement of alpha B-crystalline in tissue obtained

Stem cell markers (CD44+, CD24-, CD133, ALDH1 and evaluation of the NOTCH pathway) in tissue

Measurement of proliferation markers (Ki67)

Measurement of beta III tubulin in tissue

Measurement of Tau in tissue

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

Safety profile of this drug combination

EGFR staining before and after treatment

Full Information

NCT ID

NCT01372579

First Posted

June 1, 2011

Last Updated

June 6, 2019

Sponsor

Northwestern University

Collaborators

Eisai Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01372579

Brief Title

Carboplatin and Eribulin Mesylate in Triple Negative Breast Cancer Patients

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2019

Overall Recruitment Status

Unknown status

Study Start Date

August 2011 (undefined)

Primary Completion Date

June 2020 (Anticipated)

Study Completion Date

June 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Northwestern University

Collaborators

Eisai Inc.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment (neoadjuvant chemotherapy)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

eribulin mesylate

Other Intervention Name(s)

Halaven, B1939, E7389, ER-086526, halichrondrin B analog

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

carboplatin

Other Intervention Name(s)

Carboplat, CBDCA, JM-8, Paraplat, Paraplatin

Intervention Description

Given IV

Intervention Type

Procedure

Intervention Name(s)

biopsy

Other Intervention Name(s)

biopsies

Intervention Description

Correlative studies

Primary Outcome Measure Information:

Title

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)

Secondary Outcome Measure Information:

Title

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)

Title

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)

Title

Measurement of proliferation markers (Ki67)

Time Frame

Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy)

Title

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)

Title

Measurement of Tau in tissue

Time Frame

Biopsy at baseline and tissue removed at time of surgery (after approximately 12 weeks of neoadjuvant therapy)

Title

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)

Title

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

Title

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)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Virginia Kaklamani, MD

Organizational Affiliation

Northwestern University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

26006067

Citation

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.

Results Reference

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Carboplatin and Eribulin Mesylate in Triple Negative Breast Cancer Patients

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