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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

Tracking Information
First Submitted Date  ICMJE January 31, 2012
First Posted Date  ICMJE February 7, 2012
Results First Submitted Date  ICMJE March 18, 2016
Results First Posted Date  ICMJE August 26, 2016
Last Update Posted Date November 4, 2016
Study Start Date  ICMJE June 2012
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 15, 2016)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 6, 2012)
The pCR rate of 6 cycles of neoadjuvant patients treated with ErC and TC [ Time Frame: 18 weeks ]
Change History Complete list of historical versions of study NCT01527487 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2016)
  • 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
  • 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;
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 6, 2012)
  • The toxicity profiles of ErC and TC [ Time Frame: 18 weeks ]
    This will be done through Adverse Event assessments on Day 1 and 8 of each cycle.
  • The clinical response rate of ErC as neoadjuvant therapy [ Time Frame: 18 weeks ]
  • The 2 year DFS of patients treated with ErC and TC [ Time Frame: 24 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Trial of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Locally Advanced HER2-Negative Breast Cancer
Official Title  ICMJE A Randomized Phase II Study of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Locally Advanced HER2-Negative Breast Cancer
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HER2 Negative Breast Cancer
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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
    • Drug: Cyclophosphamide
  • 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
    • Drug: Docetaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 6, 2012)
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 2016
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01527487
Other Study ID Numbers  ICMJE SCRI BRE 197
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party SCRI Development Innovations, LLC
Study Sponsor  ICMJE SCRI Development Innovations, LLC
Collaborators  ICMJE Eisai Inc.
Investigators  ICMJE
Study Chair: Denise A Yardley, MD SCRI Development Innovations, LLC
PRS Account SCRI Development Innovations, LLC
Verification Date October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP