Trial of Eribulin in Patients Who Do Not Achieve Pathologic Complete Response (pCR) Following Neoadjuvant Chemotherapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01401959
Recruitment Status : Active, not recruiting
First Posted : July 26, 2011
Last Update Posted : November 13, 2017
Eisai Inc.
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Brief Summary:
The investigators propose to evaluate eribulin as adjuvant therapy in breast cancer patients who do not achieve pCR following standard neoadjuvant chemotherapy. Three cohorts of patients will be evaluated separately based on tumor type: triple-negative, hormone-receptor-positive/HER2-negative, and HER2-positive.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: eribulin mesylate Drug: Trastuzumab Phase 2

Detailed Description:
This is a non-randomized, open-label trial to evaluate 6 cycles of eribulin in female patients with invasive breast cancer who do not achieve pathologic complete response (pCR) after treatment with a standard neoadjuvant chemotherapy regimen and surgery. Patients will be randomized into three cohorts according to tumor-type: triple-negative (Cohort A), hormone-receptor-positive/HER2-negative (Cohort B), and HER2-positive (Cohort C) tumors. Patients will receive eribulin for 6 cycles (1 cycle = 21 days). Patients with HER2-positive tumors will also receive trastuzumab; and patients in Cohort B will receive locoregional radiotherapy and/or adjuvant hormonal therapy per institutional guidelines. Up to 148 patients are planned for enrollment.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 128 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Eribulin in Patients Who Do Not Achieve Pathologic Complete Response (pCR) Following Neoadjuvant Chemotherapy
Actual Study Start Date : September 23, 2011
Actual Primary Completion Date : April 3, 2017
Estimated Study Completion Date : July 1, 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Triple-negative breast cancer
eribulin mesylate
Drug: eribulin mesylate
1.4 mg/m2 IV Days 1 and 8, every 21 days
Other Name: Halaven
Experimental: HER2-positive breast cancer

eribulin mesylate


Drug: eribulin mesylate
1.4 mg/m2 IV Days 1 and 8, every 21 days
Other Name: Halaven
Drug: Trastuzumab
6 mg/kg IV Day 1 every 21 days
Other Name: Herceptin
Experimental: ER/PR Positive/HER2-negative breast cancer
eribulin mesylate
Drug: eribulin mesylate
1.4 mg/m2 IV Days 1 and 8, every 21 days
Other Name: Halaven

Primary Outcome Measures :
  1. Two-Year Disease-Free Survival (DFS) [ Time Frame: 2 years after completion of treatment ]
    Proportion of patients who are alive without evidence of disease recurrence 24 months after completing protocol treatment.

Secondary Outcome Measures :
  1. Number of patients who complete all protocol-specified therapy without undue toxicity leading to early discontinuation or evidence of disease recurrence. [ Time Frame: 2 years ]
    Feasibility of administering 6 cycles of eribulin following standard neoadjuvant chemotherapy and primary surgical therapy will be determined by the study's principal investigator.

  2. Number of adverse events and serious adverse events as a measure of safety. [ Time Frame: up to 2 years ]
    Patients who receive any amount of trial medication will be included in the assessment of safety. Adverse events and serious adverse events will be assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V4.0.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Female patients >=18 years-of-age.
  2. Histologically confirmed breast cancer prior to surgery with the following staging criteria: T1-T3, N0-N2, and M0 (T1N0M0 patients are excluded).
  3. Previous treatment with a minimum of 4 cycles of neoadjuvant anthracycline and/or taxane containing chemotherapy (+trastuzumab in HER2-positive patients).
  4. Patients must be ≥ 21 days and ≤ 84 days from breast surgery and fully recovered. Patients may have had mastectomy or breast conservation surgery with axillary node dissection.
  5. Pathologic CR (pCR) not achieved following neoadjuvant treatment (i.e., residual invasive breast cancer (>5 mm) in the breast or presence of nodal disease at surgery [ypT0, N1-N3a, M0 or ypT1b-T4, N0-N3a, M0].
  6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
  7. Recovery from any toxic effects of prior therapy to <=Grade 1 per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03) except fatigue or alopecia.
  8. Peripheral neuropathy Grade <=2 per NCI CTCAE v4.03 at trial entry.
  9. Normal left ventricular ejection fraction (LVEF), within the institutional limits of normal, as measured by echocardiography (ECHO) or multi-gated (MUGA) scan in patients to receive trastuzumab with eribulin (Cohort C).
  10. Adequate hematologic, hepatic, and renal function
  11. Complete staging work-up to confirm localized disease should include computed tomography (CT) scans of the chest and abdomen/pelvis (abdomen/pelvis preferred; abdomen accepted), a CT scan of the head or MRI of the brain (if symptomatic), and either a positron emission tomography (PET) scan or a bone scan. (Note: a PET/CT is acceptable for baseline imaging in lieu of CT examinations or bone scan). Negative scans performed prior to the initiation of neoadjuvant therapy, or at any subsequent time, are acceptable and do not need to be repeated.
  12. Female patients who are not of child-bearing potential and female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum pregnancy test performed within 7 days prior to start of trial treatment.
  13. Willingness and ability to comply with trial and follow-up procedures.
  14. Ability to understand the investigative nature of this trial and give written informed consent.
  15. Agree to delay in reconstruction in terms of implants placed in setting of expanders until chemotherapy is completed and the patient has recovered. Expansion of expanders may continue during trial treatment.

Exclusion Criteria:

  1. Presence of other active cancers, or history of treatment for invasive cancer <3 years prior to trial entry (except thyroid, cervical cancer). Patients with Stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
  2. Radiotherapy prior to the start of study treatment.
  3. History or clinical evidence of central nervous system metastases or other metastatic disease.
  4. Non-healed surgical wound.
  5. Known or suspected allergy/hypersensitivity to eribulin.
  6. Cardiac disease, including: congestive heart failure Class II-IV per New York Heart Association classification;cardiac ventricular arrhythmias requiring anti-arrhythmic therapy; unstable angina (anginal symptoms at rest) or new-onset angina (i.e., began within the last 3 months), or myocardial infarction within the past 6 months.
  7. Chronic use of drugs that cause QTc prolongation.Patients must discontinue use of these drugs 7 days prior to the start of study treatment.
  8. Women who are pregnant or lactating. All females of child-bearing potential must have negative serum or urine pregnancy tests within 48 hours prior to trial treatment.
  9. Patients with known diagnosis of human immunodeficiency virus (HIV), hepatitis C virus, or acute or chronic hepatitis B infection.
  10. Prolongation of heart rate-corrected QT interval (QTc) >480 msecs (using Bazett's formula).
  11. Minor surgical procedures (with the exception of the placement of port-a-cath or other central venous access) performed less than 7 days prior to beginning protocol treatment.
  12. History of cerebrovascular accident including transient ischemic attack (TIA), or untreated deep venous thrombosis (DVT)/ pulmonary embolism (PE) within the past 6 months. Note: Patients with recent DVT/PE receiving treatment with a stable dose of therapeutic anti-coagulating agents are eligible.
  13. Patients may not receive any other investigational or anti-cancer treatments while participating in this trial.
  14. History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with the trial participation or investigational product(s) administration or may interfere with the interpretation of the results.
  15. Inability or unwillingness to comply with trial and/or follow-up procedures outlined in the protocol.

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01401959

United States, Florida
Florida Cancer Specialists North
Fort Myers, Florida, United States, 33916
Florida Cancer Specialists South
Fort Myers, Florida, United States, 33916
Watson Clinic Center for Cancer Care and Research
Lakeland, Florida, United States, 33805
Florida Hospital Cancer Insitute
Orlando, Florida, United States, 32804
United States, Georgia
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
United States, Indiana
Providence Medical Group
Terre Haute, Indiana, United States, 47802
United States, Kentucky
Baptist Hospital East
Louisville, Kentucky, United States, 40207
United States, Maine
Mercy Hospital
Portland, Maine, United States, 04101
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
National Capital Clinical Research Consortium
Bethesda, Maryland, United States, 20817
United States, Michigan
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, United States, 49503
United States, Nebraska
Nebraska Methodist Cancer Center
Omaha, Nebraska, United States, 68114
United States, New Jersey
Atlantic Health System
Morristown, New Jersey, United States, 07960
Hematology Oncology Associates of Northern NJ
Morristown, New Jersey, United States, 07960
United States, Ohio
Oncology Hematology Care, Inc.
Cincinnati, Ohio, United States, 45242
United States, South Carolina
South Carolina Oncology Associates
Columbia, South Carolina, United States, 29210
United States, Tennessee
Chattanooga Oncology Hematology Associates
Chattanooga, Tennessee, United States, 37404
Family Cancer Center
Collierville, Tennessee, United States, 38017
Tennessee Oncology
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Health Physician Group
Arlington, Texas, United States, 76011
The Center for Cancer and Blood Disorders
Fort Worth, Texas, United States, 76104
Sponsors and Collaborators
SCRI Development Innovations, LLC
Eisai Inc.
Study Chair: Denise A Yardley, M.D. SCRI Development Innovations, LLC

Responsible Party: SCRI Development Innovations, LLC Identifier: NCT01401959     History of Changes
Other Study ID Numbers: SCRI BRE 186
First Posted: July 26, 2011    Key Record Dates
Last Update Posted: November 13, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by SCRI Development Innovations, LLC:
Metastatic Breast Cancer
Residual Disease

Additional relevant MeSH terms:
Antineoplastic Agents