Neoadjuvant Trial of Eribulin Followed by Dose Dense Doxorubicin and Cyclophosphamide for Her2-negative, Locally Advanced Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Emory University
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Amelia Zelnak, Emory University
ClinicalTrials.gov Identifier:
NCT01498588
First received: October 13, 2011
Last updated: May 21, 2014
Last verified: May 2014
  Purpose

Previous studies have shown that chemotherapy has the same effect on treating breast cancer whether you receive it before or after surgery. Receiving chemotherapy before surgery, rather than after surgery, may allow the patient to have less extensive surgery. The purpose of this study is to identify new treatment regimens with better response rates and to find out if the combination of eribulin followed by doxorubicin and cyclophosphamide can shrink the size of the patient's breast tumor and allow you to preserve your breast. Additionally, by receiving chemotherapy before surgery, the investigators will be able to determine if your cancer is responsive to chemotherapy.


Condition Intervention Phase
Breast Neoplasms
Breast Cancer
Breast Tumors
Cancer of the Breast
Neoplasms, Breast
Tumors, Breast
Drug: Eribulin
Drug: Doxorubicin
Drug: Cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Neoadjuvant Trial of Eribulin Followed by Dose Dense Doxorubicin and Cyclophosphamide for Her2-negative, Locally Advanced Breast Cancer

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Pathologic complete response rate at the time of surgery [ Time Frame: average of 24 weeks ] [ Designated as safety issue: No ]
    patients will receive treatment for 20 weeks with primary outcome measured at the time of surgery. Surgery is typically 4-6 weeks after completion of chemotherapy, so patients will be on study for 24 weeks on average.


Secondary Outcome Measures:
  • Toxicity of chemotherapy regimen [ Time Frame: 20 weeks of chemotherapy ] [ Designated as safety issue: Yes ]
    Toxicity of chemotherapy at each physiscian visit using CTCAE criteria.


Estimated Enrollment: 47
Study Start Date: November 2011
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eribulin+Doxorubicin+Cyclobhosbhamide
Neoadjuvant Eribulin followed by dose-dense Doxorubicin and Cyclophosphamide
Drug: Eribulin
Patients will receive 4 cycles of neoadjuvant eribulin followed by 4 cycles of dose-dense doxorubicin and cyclophosphamide (AC).
Drug: Doxorubicin
Neoadjuvant Eribulin followed by dose-dense Doxorubicin andCyclophosphamide
Drug: Cyclophosphamide
Neoadjuvant Eribulin followed by dose-dense Doxorubicin and Cyclophosphamide

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed invasive breast carcinoma
  • Locally advanced breast cancer (Stage IIIA to IIIC)
  • Invasive breast cancer must be Her2-negative. If breast cancer is Her2 2+ by IHC, then FISH must be negative for Her2 gene amplification.
  • No evidence of disease outside the breast or chest wall, except ipsilateral axillary lymph nodes on staging scans (CT chest/abdomen/pelvis and bone scan or PET scan)
  • Patients must have measurable disease as defined by palpable lesion with both diameters >1cm measurable with caliper and/or a positive mammogram or ultrasound with at least one dimension >1cm. Bilateral mammogram and clip placement is required for study entry. Baseline measurements of the indicator lesions must be recorded on the Patient Registration Form. To be valid for baseline, the measurements must have been made within the 14 days if palpable. If not palpable, a mammogram or MRI must be done within 14 days. If palpable, a mammogram or MRI must be done within 2 months prior to study entry. If clinically indicated, xrays and scans must be done within 28 days of study entry.
  • ECOG performance status 0 to 1 within 14 days of study entry
  • Normal (greater than 50%) left ventricular ejection fraction (LVEF) by MUGA scan or echocardiography
  • Signed informed consent
  • Adequate organ function within 2 weeks of study entry:

    • Absolute neutrophil count >1500/mm3, Hgb >9.0 g/dl and platelet count >100,000/mm3
    • Total bilirubin < upper limit of normal
    • Creatinine < 1.5 mg/dL or calculated CrCL >50mL/min using the Cockroft Gault equation
    • SGOT(AST) or SGPT(ALT) and Alkaline Phosphatase must be within the range allowing for eligibility, as in the table below:

AST or ALT:

ALK PHOS: ≤ULN >1x but >1.5x >1.5x but ≤5x >5x ULN

≤ ULN Eligible Eligible Eligible Ineligible >1x but ≤2.5x Eligible Eligible Ineligible Ineligible >2.5x but ≤5x Eligible Ineligible Ineligible Ineligible >5x ULN Ineligible Ineligible Ineligible Ineligible

  • Patients must be over 18 years old.
  • INR < 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate.
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
  • Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation.

Exclusion Criteria:

  • Prior chemotherapy, hormonal therapy, biologic therapy, investigational agent, targeted therapy or radiation therapy for current breast cancer. Patients with history of breast cancer greater than 5 years from initial diagnosis are eligible for the study. Patients may not have received anthracycline-based chemotherapy in the past. Patients with history of DCIS are eligible if there were treated with surgery alone.
  • Medical, psychological or surgical condition which the investigator feels might compromise study participation.
  • History of previous or current malignancy at other sites with the exception of adequately treated carcinoma in-situ of the cervix or basal or squamous cell carcinoma of the skin. Patients with a history of other malignancies, who remain disease free for greater than five years are eligible.
  • Evidence of sensory and/or peripheral neuropathy > grade 1.
  • Serious, uncontrolled, concurrent infection(s).
  • Major surgery within 4 weeks of the start of study treatment, without complete recovery.
  • Pregnant or lactating women are not eligible. Women of childbearing potential must have a negative serum or urine pregnancy test completed within 7 days of study treatment. Women or men of childbearing potential not using a reliable and appropriate contraceptive method are not eligible. (Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential).
  • Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
  • Active clinically serious infection > CTCAE Grade 2.
  • Thromboembolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
  • Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug.
  • Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug.
  • Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
  • Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
  • Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01498588

Contacts
Contact: Amelia Zelnak, MD 1-888-946-7447 amela.zelnak@emory.edu

Locations
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Amelia zelnak, MD    404-778-1900    amelia.zelnak@emory.edu   
Sponsors and Collaborators
Emory University
Eisai Inc.
Investigators
Principal Investigator: Amelia Zelnak, MD Emory University Winship Cancer Institute
  More Information

No publications provided

Responsible Party: Amelia Zelnak, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT01498588     History of Changes
Other Study ID Numbers: IRB00050068, WCI1937-10
Study First Received: October 13, 2011
Last Updated: May 21, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
Breast Neoplasms
Breast Cancer
Breast Tumors
Cancer of the Breast
Neoplasms, Breast
Tumors, Breast

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Cyclophosphamide
Doxorubicin
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
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on July 09, 2014