Comparison of Neoadjuvant Chemotherapy With Weekly Paclitaxel or Eribulin Followed by A/C in Women With Locally Advanced HER2-Negative Breast Cancer

NCT01705691 | Completed Phase 2 Results

• 1 other identifier: NSABP FB-9
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 20

Brief Summary

NSABP FB-9 is a Phase II, multi-center, randomized study of eribulin or weekly paclitaxel followed by doxorubicin and cyclophosphamide (AC) as neoadjuvant therapy for women with HER2-negative, operable and locally advanced breast cancer (stage IIb and III). Patients in the control arm will receive neoadjuvant weekly paclitaxel (WP) followed by AC. The primary aim of the study is to determine the pathologic complete response (ypCR) in breast and axillary lymph nodes following completion of neoadjuvant therapy. The secondary aims include determination of the ypCR in axillary nodes, clinical complete response (ycCR) rate after eribulin or paclitaxel and after completion of neoadjuvant chemotherapy, two-year recurrence-free interval, two-year overall survival, and toxicity of the neoadjuvant regimens.

Conditions

Breast Cancer; HER2-negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response Rate (ypCR) Following Neoadjuvant Therapy in Breast and Axillary Lymph Nodes

  Percentage of patients with no histologic evidence of cancer in breast and axillary lymph nodes.

  At the time of surgery approximately 24 to 28 weeks.

Secondary Outcomes (6)

• ypCR Nodes

  At the time of surgery approximately 24 to 28 weeks.

• Clinical Overall Response (cOR)(Complete and Partial) Assessed by MRI at the Completion of WP or Eribulin (Before AC)

  12 weeks after initiation of study therapy

• Clinical Complete Response (ycCR) Following Neoadjuvant Therapy Assessed by Physical Exam at the Completion of Neoadjuvant Chemotherapy

  At approximately 24 to 28 weeks from initiation of study therapy

• Recurrence Free Interval (RFI): The Time to Occurrence of Inoperable Progressive Disease and Local, Regional, and Distant Recurrence.

  Assessed through 24 months from randomization

• 2-year Overall Survival (OS): Death From Any Cause From Time of Randomization Through 2 Years After Randomization.

  Assessed through 24 months from randomization

Study Arms (2)

Arm 1: Paclitaxel then AC

ACTIVE COMPARATOR

Paclitaxel 80 mg/m2 IV weekly for 12 doses followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles

Drug: Paclitaxel; Drug: Doxorubicin; Drug: Cyclophosphamide

Arm 2: Eribulin then AC

EXPERIMENTAL

Eribulin 1.4 mg/m2 IV on days 1 and 8 of a 21-day cycle for 4 cycles, followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles

Drug: Eribulin; Drug: Doxorubicin; Drug: Cyclophosphamide

Interventions

Paclitaxel DRUG

80 mg/m2 IV over 60 minutes weekly for 12 weeks

Arm 1: Paclitaxel then AC

Eribulin DRUG

1.4 mg/m2 IV over 2 to 5 minutes on Days 1 and 8 every 21 days for 4 cycles

Also known as: eribulin mesylate

Arm 2: Eribulin then AC

Doxorubicin DRUG

60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles

Arm 1: Paclitaxel then AC; Arm 2: Eribulin then AC

Cyclophosphamide DRUG

600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles

Arm 1: Paclitaxel then AC; Arm 2: Eribulin then AC

Eligibility Criteria

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

You may qualify if:

• Patients should have a life expectancy of at least 10 years, excluding their diagnosis of breast cancer. (Comorbid conditions should be taken into consideration, but not the diagnosis of breast cancer.)
• Patients of reproductive potential must agree to use an effective non-hormonal method of contraception during therapy and for at least 6 months after the last dose of study therapy.
• The patient must have consented to participate and must have signed and dated an appropriate Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines.
• Patients must be female.
• Patients must be \> 18 years old.
• The Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1.
• The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy or by limited incisional biopsy.
• Patients must have ER analysis performed on the primary tumor prior to randomization. If ER analysis is negative, then Progesterone Receptor (PgR) analysis must also be performed. (Patients are eligible with either hormone receptor-positive or hormone receptor-negative tumors.)
• Clinical staging, based on the assessment by physical exam, must be American Joint Committee on Cancer (AJCC) stage IIB, IIIA, IIIB, or IIIC: cT2 and cN1, cT3 and cN0 or cN1, Any cT and cN2 or cN3, cT4
• The patient must have a mass in the breast or axilla measuring greater than or equal to 2.0 cm by physical exam, unless the patient has inflammatory breast cancer, in which case measurable disease by physical exam is not required.
• At the time of randomization, blood counts performed within 4 weeks prior to randomization must meet the following criteria: Absolute Neutrophil Count (ANC) must be greater than or equal to 1200/mm3; Platelet count must be greater than or equal to 100,000/mm3; Hemoglobin must be greater than or equal to 10 g/dL.
• The following criteria for evidence of adequate hepatic function performed within 4 weeks prior to randomization must be met: total bilirubin must be less than or equal to Upper Limit of Normal (ULN) for the lab unless the patient has a bilirubin elevation \> ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin; and alkaline phosphatase must be less than or equal to 1.5 x ULN for the lab; and Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) must be less than or equal to 1.5 x ULN for the lab.
• Serum creatinine performed within 4 weeks prior to randomization must be less than or equal to 1.5 x ULN for the lab.
• Serum potassium and serum magnesium performed within 4 weeks prior to randomization must be Within Normal Limits (WNL).
• The Left Ventricular Ejection Fraction (LVEF) assessment by 2-D echocardiogram or Multigated acquisition (MUGA) scan performed within 90 days prior to randomization must be greater than or equal to 50% regardless of the facility's Lower Limit of Normal (LLN).

You may not qualify if:

• Tumor that has been determined to be HER2-positive by immunohistochemistry (3+) or by in situ hybridization (positive for gene amplification), or has been determined to be HER2-equivocal and the investigator plans to administer trastuzumab or other targeted therapy.
• Fine Needle Aspiration (FNA) alone to diagnose the primary breast cancer.
• Excisional biopsy or lumpectomy performed prior to randomization.
• Surgical axillary staging procedure prior to randomization. (Procedures that are permitted prior to study entry include: 1) FNA or core biopsy of an axillary node for any patient, and 2) although not recommended, a pre-neoadjuvant therapy Sentinal Node (SN) biopsy for patients with clinically negative axillary nodes.)
• Definitive clinical or radiologic evidence of metastatic disease. (Note: Chest imaging is mandatory for all patients within 90 days prior to randomization. Other imaging \[if required\] must have been performed within 4 weeks prior to randomization.)
• History of ipsilateral invasive breast cancer regardless of treatment or ipsilateral Ductal Carcinoma in Situ (DCIS) treated with Radiation Therapy (RT). (Patients with a history of Lobular Carcinoma in Situ (LCIS), contralateral DCIS \[regardless of RT\], or contralateral invasive breast cancer are eligible.)
• History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to randomization.
• Known metastatic disease from any malignancy (solid tumor or hematologic).
• Previous therapy with anthracyclines, taxanes, cyclophosphamide, or eribulin for any malignancy.
• Treatment including RT, chemotherapy, and/or targeted therapy, administered for the currently diagnosed breast cancer prior to randomization.
• Continued endocrine therapy such as raloxifene or tamoxifen (or other SERM) or an aromatase inhibitor. (Patients are eligible if these medications are discontinued prior to randomization.)
• Any continued sex hormonal therapy, e.g., birth control pills and ovarian hormone replacement therapy. Patients are eligible if these medications are discontinued prior to randomization.
• Requirement for chronic use of any drugs known to prolong the QT interval, including Na+ and K+ channel blockers. (Patients are eligible if these medications and/or substances can be discontinued prior to the first dose of eribulin and will not need to be resumed until after the last dose of eribulin.)
• Active hepatitis B or hepatitis C with abnormal liver function tests.
• Intrinsic lung disease resulting in dyspnea.

Sponsors & Collaborators

• NSABP Foundation Inc: lead
• Eisai Inc.: collaborator

Study Sites (20)

CCOP, Colorado Cancer Research Program, Inc.

Denver, Colorado, 80222, United States

Location

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

Phoebe Putney Memorial Hospital

Albany, Georgia, 31703, United States

Location

Memorial Health University Medical Center

Savannah, Georgia, 31404, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007, United States

Location

Providence Hospital - Southfield

Southfield, Michigan, 48075-9975, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Carolinas Medical Center/Levine Cancer Center

Charlotte, North Carolina, 28203, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Albert Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

Allegheny General Hospital/Allegheny-Singer Research Institute

Pittsburgh, Pennsylvania, 15212, United States

Location

NSABP Foundation, Inc.

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232-1305, United States

Location

Roper Hospital

Charleston, South Carolina, 29401, United States

Location

Cancer Centers of the Carolinas

Greenville, South Carolina, 29615, United States

Location

Joe Arrington Cancer Research & Treatment Center

Lubbock, Texas, 79410, United States

Location

Mary Babb Randolph Cancer Center at West Virginia University Hospitals

Morgantown, West Virginia, 26506, United States

Location

Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2W-1T8, Canada

Location

Montreal General Hospital

Montreal, Quebec, H3G 1A4, Canada

Location

Related Publications (1)

• Abraham J, Robidoux A, Tan AR, Limentani S, Sturtz K, Shalaby I, Alcorn H, Buyse ME, Wolmark N, Jacobs SA. Phase II randomized clinical trial evaluating neoadjuvant chemotherapy regimens with weekly paclitaxel or eribulin followed by doxorubicin and cyclophosphamide in women with locally advanced HER2-negative breast cancer: NSABP Foundation Study FB-9. Breast Cancer Res Treat. 2015 Jul;152(2):399-405. doi: 10.1007/s10549-015-3466-4. Epub 2015 Jul 1.

  PMID: 26126970 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; eribulin; Doxorubicin; Cyclophosphamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Diana Gosik
• Organization: NSABP Foundation, Inc.

diana.gosik@nsabp.org

412-339-5333

Study Officials

• Norman Wolmark, MD

  NSABP Foundation Inc

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: October 8, 2012
• First Posted: October 12, 2012
• Study Start: September 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: October 1, 2015
• Last Updated: October 6, 2021
• Results First Posted: September 18, 2018

Record last verified: 2021-10

Locations

CA (2); US (18)