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

HER2 Negative Breast Cancer Clinical Trial

Official title:

A Randomized Phase II Study of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Locally Advanced HER2-Negative Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01527487
• Other study ID #: SCRI BRE 197
• Status: Active, not recruiting
• Phase: Phase 2
• First received: January 31, 2012
• Last updated: January 5, 2016
• Start date: June 2012
• Est. completion date: March 2016

Study information

• Verified date: January 2016
• Source: SCRI Development Innovations, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 77
• Est. completion date: March 2016
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically confirmed invasive adenocarcinoma of the breast.

2. 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.

3. Patients entering the trial after undergoing an axillary node dissection will be eligible if they meet other entry criteria.

4. Estrogen receptor (ER) and progesterone receptor (PR) status in the primary tumor known or pending at the time of study registration.

5. 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.

6. Bilateral, synchronous breast cancer is allowed if both primary tumors are HER2-negative and at least one meets the specified qualifying tumor or nodal inclusion criteria.

7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-2.

8. 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.

9. No evidence of metastatic disease, as documented by complete staging workup =8 weeks prior to initiation of study treatment.

10. No prior treatment for this breast cancer with the exception of criterion #3.

11. 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)

12. Adequate hematologic function defined as:

• Absolute neutrophil count (ANC) =1500/µL

• Hemoglobin (Hgb) =10 g/dL

• Platelets =100,000/uL

13. Adequate liver function defined as:

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5 x the upper limit of normal (ULN)

• Total bilirubin = the institutional ULN

14. Adequate renal function defined as:

• Serum creatinine =1.5 mg/dL x ULN OR calculated creatinine clearance =50 mL/min by the Cockcroft-Gault method:

GRF =(140-age) x (weight/kg) x (0.85 if female) (72 x serum creatinine mg/dL)

15. Other laboratory testing:

• Serum magnesium = the institutional lower limit of normal (LLN)

• Serum potassium =the institutional LLN

16. Female and =18 years of age.

17. Negative serum pregnancy test within <7 days prior to initial trial treatment.

18. Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures that are approved by their study physician while receiving study treatment and continuing for 3 weeks after the last dose of study drug treatment, who are not breastfeeding, and who have a negative serum pregnancy test prior to start of dosing.

19. Willingness and ability to comply with trial and follow-up procedures.

20. Ability to understand the nature of this trial and give written informed consent.

Exclusion Criteria:

1. Clinical T4 lesions, including inflammatory breast cancer. Clinical N3 involvement (e.g., ipsilateral, infraclavicular, supraclavicular, and internal mammary nodes).

2. Peripheral neuropathy (motor or sensory) > grade 1 according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).

3. Patient has received radiotherapy for treatment of previous cancer that included =30% of major bone marrow containing areas (e.g., pelvis, lumbar, spine).

4. Known or suspected allergy or hypersensitivity to any of the study drugs (i.e., eribulin, cyclophosphamide, docetaxel) or known hypersensitivity to polysorbate 80.

5. Patients with acute or chronic liver or renal disease or pancreatitis.

6. Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B (HBV) or Hepatitis C (HCV).

7. 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).

8. 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).

• Valvular disease with significant compromise in cardiac function

9. Chronic use of drugs that cause QTc prolongation. Patients must discontinue use of these drugs 7 days prior to the start of study treatment.

10. Presence of other active cancers, or history of treatment for invasive cancer =5 years. Patients with stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e. non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.

11. Patients may not receive any other investigational or anti-cancer treatments while participating in this trial.

12. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

13. Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• HER2 Negative Breast Cancer

Intervention

Drug:
• Eribulin
1.4 mg/m2 IV (Days 1 & 8), given short (=15 minute) IV infusion, per institutional standard
• Cyclophosphamide
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.
• Docetaxel
Patients assigned to Treatment Arm 2 will receive docetaxel 75 mg/m2 IV on Day 1 of each treatment cycle every 3 weeks.

Locations

Country	Name	City	State
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	Oncology Hematology Care, Inc	Cincinnati	Ohio
United States	South Carolina Oncology Associates	Columbia	South Carolina
United States	The Center for Cancer and Blood Disorders	Fort Worth	Texas
United States	Florida Cancer Specialists South	Ft. Myers	Florida
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Grand Rapids Oncology Program	Grand Rapids	Michigan
United States	Memorial Cancer Institute	Hollywood	Florida
United States	Research Medical Center	Kansas City	Missouri
United States	Tennessee Oncology	Nashville	Tennessee
United States	Nebraska Methodist Cancer Center	Omaha	Nebraska
United States	Woodlands Medical Specialists	Pensacola	Florida
United States	Mercy Hospital	Portland	Maine
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Florida Cancer Specialists North	St. Petersburg	Florida

Sponsors (2)

Lead Sponsor	Collaborator
SCRI Development Innovations, LLC	Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The pCR rate of 6 cycles of neoadjuvant patients treated with ErC and TC		18 weeks	No
Secondary	The number of adverse events as a measure of safety and tolerability.	Toxicity profiles of Erc and TC assessed on Day 1 and 8 of each 21-day cycle.	18 weeks	Yes
Secondary	The clinical response rate of ErC as neoadjuvant therapy	Defined as the number of patients with a best clinical complete or partial response (CR or PR) divided by the number of patients qualified for tumor response analysis.	18 weeks	No
Secondary	Disease-Free Survival (DFS) at 2 years	Defined as the time between surgery and date of first documented disease recurrence or death from any cause.	24 months	No