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

This study is currently recruiting participants.
Verified December 2013 by SCRI Development Innovations, LLC
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT01527487
First received: January 31, 2012
Last updated: December 2, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Locally Advanced HER2-Negative Breast Cancer
Drug: Eribulin Mesylate
Drug: Cyclophosphamide
Drug: Docetaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • The pCR rate of 6 cycles of neoadjuvant patients treated with ErC and TC [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The toxicity profiles of ErC and TC [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • The 2 year Disease-Free Survival (DFS) of patients treated with ErC and TC [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 76
Study Start Date: June 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: Eribulin/ Cyclophosphamide (ErC) Drug: Eribulin Mesylate
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: Arm 2: Docetaxel/Cyclophosphamide (TC) 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

  Eligibility

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

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01527487

Contacts
Contact: ASK SARAH 1-877-691-7274 asksarah@scresearch.net

Locations
United States, Florida
Florida Cancer Specialists South Recruiting
Ft. Myers, Florida, United States, 33916
Principal Investigator: Gail Wright         
Memorial Cancer Institute Recruiting
Hollywood, Florida, United States, 33021
Principal Investigator: Aruna Mani         
Woodlands Medical Specialists Recruiting
Pensacola, Florida, United States, 32503
Principal Investigator: Rami Owera, MD         
Florida Cancer Specialists North Recruiting
St. Petersburg, Florida, United States, 33705
Principal Investigator: Lowell Hart, MD         
United States, Georgia
Northeast Georgia Medical Center Recruiting
Gainesville, Georgia, United States, 30501
Contact: Patti Rotunda    770-219-8826    patti.rotunda@nghs.com   
Principal Investigator: Andre Kallab, MD         
United States, Maine
Mercy Hospital Recruiting
Portland, Maine, United States, 04102
Principal Investigator: Roger Inhorn, MD         
United States, Maryland
Center for Cancer and Blood Disorders Recruiting
Bethesda, Maryland, United States, 20817
Contact: Natalie Bongiorno    301-571-2016    nbongiorno@ccbdmd.com   
Principal Investigator: Victor Priego, MD         
United States, Michigan
Grand Rapids Oncology Program Recruiting
Grand Rapids, Michigan, United States, 49503
Contact: Connie Szczepanek    616-391-1230    connie.szczepanek@grcop.org   
Principal Investigator: Gilbert Padula, MD         
United States, Missouri
Research Medical Center Recruiting
Kansas City, Missouri, United States, 64132
Contact: Jennifer Feeback    816-276-4227    jennifer.feeback@hcamidwest.com   
Principal Investigator: Stephanie Graff, MD         
United States, Nebraska
Nebraska Methodist Cancer Center Recruiting
Omaha, Nebraska, United States, 68114
Contact: Kim Bland    402-354-5144    kim.bland@nmhs.org   
Principal Investigator: Robert Langdon, MD         
United States, Ohio
Oncology Hematology Care, Inc Recruiting
Cincinnati, Ohio, United States, 45242
Principal Investigator: Patrick Ward, MD         
United States, South Carolina
South Carolina Oncology Associates Recruiting
Columbia, South Carolina, United States, 29210
Principal Investigator: William Butler, MD         
United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Principal Investigator: Denise Yardley, MD         
United States, Texas
The Center for Cancer and Blood Disorders Recruiting
Fort Worth, Texas, United States, 76104
Contact: Joyce Wallace    817-759-7022    jwallace@txcc.com   
Principal Investigator: Robin Young, MD         
United States, Virginia
Virginia Cancer Institute Recruiting
Richmond, Virginia, United States, 23230
Contact: George Orr    804-288-7159    gorr@vacancer.com   
Principal Investigator: James Khatcheressian, MD         
Sponsors and Collaborators
SCRI Development Innovations, LLC
Eisai Inc.
Investigators
Study Chair: Denise A Yardley, MD SCRI Development Innovations, LLC
  More Information

No publications provided

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT01527487     History of Changes
Other Study ID Numbers: SCRI BRE 197
Study First Received: January 31, 2012
Last Updated: December 2, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Docetaxel
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on April 16, 2014