- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01498588
Trial of Eribulin Followed by Doxorubicin & Cyclophosphamide for Her2-negative, Locally Advanced Breast Cancer
Phase II Neoadjuvant Trial of Eribulin Followed by Dose Dense Doxorubicin and Cyclophosphamide for Her2-negative, Locally Advanced Breast Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a phase 2, single-arm, open label study. Patients with Her2-negative, locally advanced breast cancer will be enrolled on the study prior to receiving neoadjuvant chemotherapy. Patients will receive 4 cycles of neoadjuvant eribulin followed by 4 cycles of dose-dense doxorubicin and cyclophosphamide (AC).
All patients will have a baseline biopsy prior to study entry to determine eligibility. Patients will undergo repeat breast imaging and optional biopsy after completing 4 cycles of eribulin. Patients will then receive 4 cycles of dose-dense AC. Patients will undergo repeat breast imaging followed by surgical resection within 30 days of completing last cycle of chemotherapy. Patients who are not surgical candidates after completion of chemotherapy will be asked to undergo optional repeat biopsy prior to receiving additional treatment at the discretion of the investigator. Patients will continue to be followed per standard practice guideline after surgery
Clinical response will be determined by clinical breast examination prior to each cycle of chemotherapy and by breast imaging performed at baseline, after completion of eribulin, and prior to surgery. Pathologic complete response (pCR) will be determined at the time of surgical resection. Correlative biomarker studies will be performed on tumor samples at the completion of the clinical trial.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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Georgia
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Atlanta, Georgia, United States, 30303
- Grady Memorial Hospital
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Atlanta, Georgia, United States, 30308
- Emory University Hospital Midtown
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Atlanta, Georgia, United States, 30322
- Emory University Winship Cancer Institute
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Wisconsin
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Madison, Wisconsin, United States, 53792
- University of Wisconsin Carbone Cancer Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 immunohistochemistry (IHC), then fluorescence in situ hybridization (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 positron emission tomography [PET] scan).
- Patients must have measurable disease as defined by palpable lesion with both diameters ≥ 1 cm measurable with caliper and/or a positive mammogram or ultrasound with at least one dimension ≥ 1 cm. 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.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 within 14 days of study entry.
- Normal (greater than 50%) left ventricular ejection fraction (LVEF) by multigated acquisition (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 creatinine clearance rate (CrCL) ≥ 50 mL/min using the Cockroft Gault equation.
- Serum glutamate oxaloacetate transaminase (SGOT)/(AST) or serum glutamate pyruvate transaminase (SGPT)/(ALT) and alkaline phosphatase (alk phos) must be within the range allowing for eligibility.
- Patients must be over 18 years old.
- International normalized ratio (INR) < 1.5 or a prothrombin time (PT)/partial thromboplastin time (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.
- Patient must have signed informed consent prior to registration on this study.
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 ductal carcinoma in situ (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 New York Heart Association (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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Eribulin+Doxorubicin+Cyclophosphamide
Neoadjuvant eribulin followed by dose-dense doxorubicin and cyclophosphamide Eribulin Day 1 and Day 8 of a 21 day cycle x 4 cycles: Day 1: Eribulin 1.4mg/m² IV Day 8: Eribulin 1.4mg/m² IV Dose-dense doxorubicin and cyclophosphamide every 14 days x 4 cycles: Day 1: Doxorubicin 60mg/m² IV Day 1: Cyclophosphamide 600mg/m² IV Day 2: Pegfilgrastim support 6mg sc at least 24 hours after chemotherapy at the discretion of the investigator. |
Patients will receive 4 cycles of neoadjuvant eribulin followed by 4 cycles of dose-dense doxorubicin and cyclophosphamide (AC).
Other Names:
Neoadjuvant eribulin followed by dose-dense doxorubicin and cyclophosphamide
Other Names:
Neoadjuvant eribulin followed by dose-dense doxorubicin and cyclophosphamide
Other Names:
Growth factor support (pegfilgrastim) can be given at the discretion of the investigator.
Administration of pegfilgrastim is required 24 to 48 hours following administration of dose-dense doxorubicin and cyclophosphamide.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pathologic Complete Response Rate at the Time of Surgery
Time Frame: Average of 24 weeks
|
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.
Response was measured by pathologist's standard of care assessment of extent of residual disease.
If the patient had no evidence of invasive or in situ residual disease present in the breast and lymph node (i.e.
ypT0N0), then this was defined as a pathologic complete response (pCR).
Reported is the number of participants showing pCR.
|
Average of 24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Toxicity of Chemotherapy Regimen (Number of Participants With Any Adverse Events)
Time Frame: Through 20 weeks of chemotherapy
|
Toxicity of chemotherapy at each physician visit using Common Toxicity Criteria for Adverse Effects (CTCAE) criteria.
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Through 20 weeks of chemotherapy
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Keerthi Gogineni, MD, MSHP, Emory University Winship Cancer Institute
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms by Site
- Breast Diseases
- Neoplasms
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antibiotics, Antineoplastic
- Cyclophosphamide
- Doxorubicin
Other Study ID Numbers
- IRB00050068
- WCI1937-10 (OTHER: Other)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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