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

NCT01527487 | Completed Phase 2 Results DMC

• 1 other identifier: SCRI BRE 197
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

HER2 Negative Breast Cancer

Keywords

breast cancer; eribulin; Halaven; taxotere

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response (pCR) Rate in Patients Treated With ErC for 6 Cycles Prior to Surgery

  One cycle = 21 days. Pathologic CR is defined as the absence of invasive tumor in the breast and lymph node tissue removed at the time of definitive surgery as judged by the local pathologist.

  18 weeks

Secondary Outcomes (3)

• The Number of Adverse Events as a Measure of Safety and Tolerability.

  43 months

• Clinical Response Rate (cRR) of ErC as Neoadjuvant Therapy

  43 months

• Disease-Free Survival (DFS) at 2 Years

  24 months

Study Arms (2)

Eribulin+Cyclophosphamide (ErC)

EXPERIMENTAL

Eribulin (Er): 1.4mg/m2 IV (Days 1 and 8) given short (≤1.5 minutes) IV infusion, per institutional standard Cyclophosphamide (C): 600 mg/m2 IV (Day 1), given by IV infusion, per institutional standard

Drug: Eribulin; Drug: Cyclophosphamide

Docetaxel+Cyclophosphamide (TC)

EXPERIMENTAL

Docetaxel (T): 75 mg/m2 IV (Day 1), given by 1-hour IV infusion Cyclophosphamide (C): 600 mg/m2 IV (Day 1), given by IV infusion, per institutional standard

Drug: Cyclophosphamide; Drug: Docetaxel

Interventions

Eribulin DRUG

1.4 mg/m2 IV (Days 1 \& 8), given short (≤15 minute) IV infusion, per institutional standard

Also known as: Halaven

Eribulin+Cyclophosphamide (ErC)

Cyclophosphamide DRUG

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.

Also known as: Cytoxan

Docetaxel+Cyclophosphamide (TC); Eribulin+Cyclophosphamide (ErC)

Docetaxel DRUG

Patients assigned to Treatment Arm 2 will receive docetaxel 75 mg/m2 IV on Day 1 of each treatment cycle every 3 weeks.

Also known as: Taxotere

Docetaxel+Cyclophosphamide (TC)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed invasive adenocarcinoma of the breast.
• 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.
• Patients entering the trial after undergoing an axillary node dissection will be eligible if they meet other entry criteria.
• Estrogen receptor (ER) and progesterone receptor (PR) status in the primary tumor known or pending at the time of study registration.
• 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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-2.
• 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.
• No evidence of metastatic disease, as documented by complete staging workup ≤8 weeks prior to initiation of study treatment.
• No prior treatment for this breast cancer with the exception of criterion #3.
• 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)
• Adequate hematologic function defined as:
• Absolute neutrophil count (ANC) ≥1500/μL
• Hemoglobin (Hgb) ≥10 g/dL

You may not qualify if:

• Clinical T4 lesions, including inflammatory breast cancer. Clinical N3 involvement (e.g., ipsilateral, infraclavicular, supraclavicular, and internal mammary nodes).
• Peripheral neuropathy (motor or sensory) \> grade 1 according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).
• Patient has received radiotherapy for treatment of previous cancer that included ≥30% of major bone marrow containing areas (e.g., pelvis, lumbar, spine).
• Known or suspected allergy or hypersensitivity to any of the study drugs (i.e., eribulin, cyclophosphamide, docetaxel) or known hypersensitivity to polysorbate 80.
• Patients with acute or chronic liver or renal disease or pancreatitis.
• Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B (HBV) or Hepatitis C (HCV).
• 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).
• 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).

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Eisai Inc.: collaborator

Study Sites (15)

Florida Cancer Specialists South

Fort Myers, Florida, 33916, United States

Location

Memorial Cancer Institute

Hollywood, Florida, 33021, United States

Location

Woodlands Medical Specialists

Pensacola, Florida, 32503, United States

Location

Florida Cancer Specialists North

St. Petersburg, Florida, 33705, United States

Location

Northeast Georgia Medical Center

Gainesville, Georgia, 30501, United States

Location

Mercy Hospital

Portland, Maine, 04102, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Grand Rapids Oncology Program

Grand Rapids, Michigan, 49503, United States

Location

Research Medical Center

Kansas City, Missouri, 64132, United States

Location

Nebraska Methodist Cancer Center

Omaha, Nebraska, 68114, United States

Location

Oncology Hematology Care, Inc

Cincinnati, Ohio, 45242, United States

Location

South Carolina Oncology Associates

Columbia, South Carolina, 29210, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

The Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

Virginia Cancer Institute

Richmond, Virginia, 23230, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

eribulin; Cyclophosphamide; Docetaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Diterpenes; Terpenes

Results Point of Contact

• Title: John D Hainsworth, MD
• Organization: Sarah Cannon Research Institute

asksarah@scresearch.net

1-877-691-7274

Study Officials

• Denise A Yardley, MD

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2012
• First Posted: February 7, 2012
• Study Start: June 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: July 1, 2016
• Last Updated: November 4, 2016
• Results First Posted: August 26, 2016

Record last verified: 2016-10

Locations

US (15)