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

NCT01498588 | Terminated Phase 2 Results DMC

• 2 other identifiers: IRB00050068WCI1937-10
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Breast Neoplasms; Breast Cancer; Breast Tumors; Cancer of the Breast; Neoplasms, Breast; Tumors, Breast

Keywords

Breast Neoplasms; Breast Cancer; Breast Tumors; Cancer of the Breast; Neoplasms, Breast; Tumors, Breast

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Toxicity of Chemotherapy Regimen (Number of Participants With Any Adverse Events)

  Through 20 weeks of chemotherapy

Study Arms (1)

Eribulin+Doxorubicin+Cyclophosphamide

EXPERIMENTAL

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.

Drug: Eribulin; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Pegfilgrastim

Interventions

Eribulin DRUG

Patients will receive 4 cycles of neoadjuvant eribulin followed by 4 cycles of dose-dense doxorubicin and cyclophosphamide (AC).

Also known as: Halaven

Eribulin+Doxorubicin+Cyclophosphamide

Doxorubicin DRUG

Neoadjuvant eribulin followed by dose-dense doxorubicin and cyclophosphamide

Also known as: Adriamycin

Eribulin+Doxorubicin+Cyclophosphamide

Cyclophosphamide DRUG

Neoadjuvant eribulin followed by dose-dense doxorubicin and cyclophosphamide

Also known as: Cytoxan

Eribulin+Doxorubicin+Cyclophosphamide

Pegfilgrastim DRUG

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.

Also known as: Neulasta

Eribulin+Doxorubicin+Cyclophosphamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Emory University: lead
• Eisai Inc.: collaborator

Study Sites (4)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

eribulin; Doxorubicin; Cyclophosphamide; pegfilgrastim

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

Study accrual was low at 7 patients.

Results Point of Contact

• Title: Keerthi Gogineni, MD, MSHP
• Organization: Emory University

keerthi.gogineni@emory.edu

404-778-1801

Study Officials

• Keerthi Gogineni, MD, MSHP

  Emory University Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 13, 2011
• First Posted: December 23, 2011
• Study Start: November 1, 2011
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: October 3, 2016
• Results First Posted: October 3, 2016

Record last verified: 2016-09

Locations

US (4)