Trial of Eribulin Followed by Doxorubicin & Cyclophosphamide for Her2-negative, Locally Advanced Breast Cancer

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01498588
• Other study ID #: IRB00050068
• Secondary ID: WCI1937-10
• Status: Terminated
• Phase: Phase 2
• First received: October 13, 2011
• Last updated: September 28, 2016
• Start date: November 2011
• Est. completion date: June 2015

Study information

• Verified date: September 2016
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Data and Safety Monitoring BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Breast Tumors
• Cancer of the Breast
• Neoplasms
• Neoplasms, Breast
• Tumors, Breast

Intervention

Drug:
• Eribulin
Patients will receive 4 cycles of neoadjuvant eribulin followed by 4 cycles of dose-dense doxorubicin and cyclophosphamide (AC).
• Doxorubicin
Neoadjuvant eribulin followed by dose-dense doxorubicin and cyclophosphamide
• Cyclophosphamide
Neoadjuvant eribulin followed by dose-dense doxorubicin and cyclophosphamide
• Pegfilgrastim
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.

Locations

Country	Name	City	State
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Winship Cancer Institute	Atlanta	Georgia
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic Complete Response Rate at the Time of Surgery	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	No
Secondary	Toxicity of Chemotherapy Regimen (Number of Participants With Any Adverse Events)	Toxicity of chemotherapy at each physician visit using Common Toxicity Criteria for Adverse Effects (CTCAE) criteria.	Through 20 weeks of chemotherapy	Yes