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Trial of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Locally Advanced HER2-Negative Breast Cancer

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: NCT01527487
Recruitment Status : Completed
First Posted : February 7, 2012
Results First Posted : August 26, 2016
Last Update Posted : November 4, 2016
Eisai Inc.
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Brief Summary:
The investigators propose a randomized phase II study evaluating the pCR and toxicity profiles of combination eribulin/cyclophosphamide (ErC) and docetaxel /cyclophosphamide (TC) as neoadjuvant therapy for locally advanced HER2-negative breast cancer.

Condition or disease Intervention/treatment Phase
HER2 Negative Breast Cancer Drug: Eribulin Drug: Cyclophosphamide Drug: Docetaxel Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Locally Advanced HER2-Negative Breast Cancer
Study Start Date : June 2012
Actual Primary Completion Date : September 2014
Actual Study Completion Date : July 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Eribulin+Cyclophosphamide (ErC)

Eribulin (Er): 1.4mg/m2 IV (Days 1 and 8) given short (≤1.5 minutes) IV infusion, per institutional standard

Cyclophosphamide (C): 600 mg/m2 IV (Day 1), given by IV infusion, per institutional standard

Drug: Eribulin
1.4 mg/m2 IV (Days 1 & 8), given short (≤15 minute) IV infusion, per institutional standard
Other Name: Halaven

Drug: Cyclophosphamide
Cyclophosphamide will be given as an IV infusion (600 mg/m2) on Day 1 of each treatment cycle over approximately 30 minutes, or per institutional standard.
Other Name: Cytoxan

Experimental: Docetaxel+Cyclophosphamide (TC)

Docetaxel (T): 75 mg/m2 IV (Day 1), given by 1-hour IV infusion

Cyclophosphamide (C): 600 mg/m2 IV (Day 1), given by IV infusion, per institutional standard

Drug: Cyclophosphamide
Cyclophosphamide will be given as an IV infusion (600 mg/m2) on Day 1 of each treatment cycle over approximately 30 minutes, or per institutional standard.
Other Name: Cytoxan

Drug: Docetaxel
Patients assigned to Treatment Arm 2 will receive docetaxel 75 mg/m2 IV on Day 1 of each treatment cycle every 3 weeks.
Other Name: Taxotere

Primary Outcome Measures :
  1. Pathologic Complete Response (pCR) Rate in Patients Treated With ErC for 6 Cycles Prior to Surgery [ Time Frame: 18 weeks ]
    One cycle = 21 days. Pathologic CR is defined as the absence of invasive tumor in the breast and lymph node tissue removed at the time of definitive surgery as judged by the local pathologist.

Secondary Outcome Measures :
  1. The Number of Adverse Events as a Measure of Safety and Tolerability. [ Time Frame: 43 months ]
    Treatment-Related Adverse Events occurring in >= 15% of treated patients

  2. Clinical Response Rate (cRR) of ErC as Neoadjuvant Therapy [ Time Frame: 43 months ]
    Defined as the number of patients with a best response of clinical complete or partial response (cCR or cPR) divided by the number of patients qualified for tumor response analysis per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) v1.1 for target lesions and assessed by MRI or CT. Complete Response (CR) defined as disappearance of all target lesions; Partial Response (PR) defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD;

  3. Disease-Free Survival (DFS) at 2 Years [ Time Frame: 24 months ]
    Defined as the percent probability that participants had not experienced disease recurrence or died from any cause at 2 years post-surgery, analyzed by Kaplan-Meier methodology.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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

Inclusion Criteria:

  1. Histologically confirmed invasive adenocarcinoma of the breast.
  2. Primary palpable disease confined to the breast and axilla on physical examination (clinical Stage II or III disease). For patients without clinically suspicious axillary adenopathy, the primary must be >2 cm in diameter by physical examination or imaging studies (clinical T2-3, N0-2, M0). For patients with clinically suspicious axillary adenopathy, the primary breast tumor can be any size (clinical T1-3, N1-2, M0). Patients who have had axillary node dissection and have pN3a (i.e. ≥10 involved axillary nodes) are also eligible.
  3. Patients entering the trial after undergoing an axillary node dissection will be eligible if they meet other entry criteria.
  4. Estrogen receptor (ER) and progesterone receptor (PR) status in the primary tumor known or pending at the time of study registration.
  5. Resolution of all acute effects of surgical procedures to ≤ grade 1. For patients who had or will have, a sentinel node and/or axillary node dissection, completion at least 1 week prior to the initiation of study treatment with a well-healed wound is required.
  6. Bilateral, synchronous breast cancer is allowed if both primary tumors are HER2-negative and at least one meets the specified qualifying tumor or nodal inclusion criteria.
  7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-2.
  8. Patients entering this study must be willing to provide release of tumor tissue collected at baseline during a diagnostic procedure if available, and at the time of future surgical procedure(s) for correlative testing. If tissue is not available, the patient will still be eligible for enrollment to the study.
  9. No evidence of metastatic disease, as documented by complete staging workup ≤8 weeks prior to initiation of study treatment.
  10. No prior treatment for this breast cancer with the exception of criterion #3.
  11. HER2-negative tumor status defined as:

    • Immunohistochemical (IHC) 0-1+ or
    • IHC 2+ or IHC 3+ confirmed as FISH (Fluorescence in situ hybridization) or SISH (Silver in situ hybridization) negative (defined by ratio <2.2)
  12. Adequate hematologic function defined as:

    • Absolute neutrophil count (ANC) ≥1500/μL
    • Hemoglobin (Hgb) ≥10 g/dL
    • Platelets ≥100,000/uL
  13. Adequate liver function defined as:

    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x the upper limit of normal (ULN)
    • Total bilirubin ≤ the institutional ULN
  14. Adequate renal function defined as:

    • Serum creatinine ≤1.5 mg/dL x ULN OR calculated creatinine clearance ≥50 mL/min by the Cockcroft-Gault method:

    GRF =(140-age) x (weight/kg) x (0.85 if female) (72 x serum creatinine mg/dL)

  15. Other laboratory testing:

    • Serum magnesium ≥ the institutional lower limit of normal (LLN)
    • Serum potassium ≥the institutional LLN
  16. Female and ≥18 years of age.
  17. Negative serum pregnancy test within <7 days prior to initial trial treatment.
  18. Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures that are approved by their study physician while receiving study treatment and continuing for 3 weeks after the last dose of study drug treatment, who are not breastfeeding, and who have a negative serum pregnancy test prior to start of dosing.
  19. Willingness and ability to comply with trial and follow-up procedures.
  20. Ability to understand the nature of this trial and give written informed consent.

Exclusion Criteria:

  1. Clinical T4 lesions, including inflammatory breast cancer. Clinical N3 involvement (e.g., ipsilateral, infraclavicular, supraclavicular, and internal mammary nodes).
  2. Peripheral neuropathy (motor or sensory) > grade 1 according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).
  3. Patient has received radiotherapy for treatment of previous cancer that included ≥30% of major bone marrow containing areas (e.g., pelvis, lumbar, spine).
  4. Known or suspected allergy or hypersensitivity to any of the study drugs (i.e., eribulin, cyclophosphamide, docetaxel) or known hypersensitivity to polysorbate 80.
  5. Patients with acute or chronic liver or renal disease or pancreatitis.
  6. Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B (HBV) or Hepatitis C (HCV).
  7. Concurrent treatment with an ovarian hormonal replacement therapy or with hormonal agents such as raloxifene, tamoxifen or other selective estrogen receptor modulator (SERM). Patients must have discontinued use of such agents prior to beginning study treatment. However, use of GNRH agonists for the purpose of fertility preservation or suppression of heavy menses is permitted (see Section 5.4.1).
  8. Patient has any of the following cardiac diseases currently or within the last 6 months:

    • Left Ventricular Ejection Fraction (LVEF) <45% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
    • Heart rate-corrected QT interval (QTc) > 480 ms on screening electrocardiogram (ECG) (using Bazett's formula)
    • Unstable angina pectoris
    • Congestive heart failure (New York Heart Association [NYHA] ≥ Grade 2
    • Acute myocardial infarction
    • Conduction abnormality not controlled with pacemaker or medication
    • Significant ventricular or supraventricular arrhythmias (Patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).
    • Valvular disease with significant compromise in cardiac function
  9. Chronic use of drugs that cause QTc prolongation. Patients must discontinue use of these drugs 7 days prior to the start of study treatment.
  10. Presence of other active cancers, or history of treatment for invasive cancer ≤5 years. 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.
  11. Patients may not receive any other investigational or anti-cancer treatments while participating in this trial.
  12. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
  13. Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.

Information from the National Library of Medicine

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): NCT01527487

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United States, Florida
Florida Cancer Specialists South
Ft. Myers, Florida, United States, 33916
Memorial Cancer Institute
Hollywood, Florida, United States, 33021
Woodlands Medical Specialists
Pensacola, Florida, United States, 32503
Florida Cancer Specialists North
St. Petersburg, Florida, United States, 33705
United States, Georgia
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
United States, Maine
Mercy Hospital
Portland, Maine, United States, 04102
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, Michigan
Grand Rapids Oncology Program
Grand Rapids, Michigan, United States, 49503
United States, Missouri
Research Medical Center
Kansas City, Missouri, United States, 64132
United States, Nebraska
Nebraska Methodist Cancer Center
Omaha, Nebraska, United States, 68114
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
Tennessee Oncology
Nashville, Tennessee, United States, 37203
United States, Texas
The Center for Cancer and Blood Disorders
Fort Worth, Texas, United States, 76104
United States, Virginia
Virginia Cancer Institute
Richmond, Virginia, United States, 23230
Sponsors and Collaborators
SCRI Development Innovations, LLC
Eisai Inc.
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Study Chair: Denise A Yardley, MD SCRI Development Innovations, LLC

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Responsible Party: SCRI Development Innovations, LLC Identifier: NCT01527487    
Other Study ID Numbers: SCRI BRE 197
First Posted: February 7, 2012    Key Record Dates
Results First Posted: August 26, 2016
Last Update Posted: November 4, 2016
Last Verified: October 2016
Keywords provided by SCRI Development Innovations, LLC:
breast cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators