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

Overview[ - collapse ][ - ]

Purpose 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.
ConditionBreast Cancer
HER2-negative Breast Cancer
InterventionDrug: Paclitaxel
Drug: Eribulin
Drug: Doxorubicin
Drug: Cyclophosphamide
PhasePhase 2
SponsorNational Surgical Adjuvant Breast and Bowel Project (NSABP)
Responsible PartyNational Surgical Adjuvant Breast and Bowel Project (NSABP)
ClinicalTrials.gov IdentifierNCT01705691
First ReceivedOctober 8, 2012
Last UpdatedAugust 29, 2013
Last verifiedAugust 2013

Tracking Information[ + expand ][ + ]

First Received DateOctober 8, 2012
Last Updated DateAugust 29, 2013
Start DateSeptember 2012
Estimated Primary Completion DateFebruary 2015
Current Primary Outcome MeasuresPathologic complete response rate (ypCR) following neoadjuvant therapy in breast and axillary lymph nodes [Time Frame: At the time of surgery approximately 24 to 28 weeks.] [Designated as safety issue: No]No histologic evidence of cancer.
Current Secondary Outcome Measures
  • ypCR nodes [Time Frame: At the time of surgery approximately 24 to 28 weeks.] [Designated as safety issue: No]
  • Clinical overall response (cOR)(complete and partial) assessed by physical exam and MRI at the completion of WP or eribulin (before AC) [Time Frame: 12 weeks after initiation of study therapy] [Designated as safety issue: No]
  • Clinical Complete Response (ycCR) following neoadjuvant therapy assessed by physical exam at the completion of neoadjuvant chemotherapy [Time Frame: At approximately 24 to 28 weeks from initiation of study therapy] [Designated as safety issue: No]
  • Recurrence Free Interval (RFI): The time to occurrence of inoperable progressive disease and local, regional, and distant recurrence. [Time Frame: Assessed through 24 months from randomization] [Designated as safety issue: No]
  • 2-year Overall Survival (OS): Death from any cause from time of randomization through 2 years after randomization. [Time Frame: Assessed through 24 months from randomization] [Designated as safety issue: No]
  • Adverse events experienced by participants as a measure of toxicity. [Time Frame: Assessed through 24 months from randomization] [Designated as safety issue: Yes]

Descriptive Information[ + expand ][ + ]

Brief TitleComparison of Neoadjuvant Chemotherapy With Weekly Paclitaxel or Eribulin Followed by A/C in Women With Locally Advanced HER2-Negative Breast Cancer
Official TitleA 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
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.
Detailed Description
Patients will be randomized to one of two neoadjuvant therapy regimens. Patients in Arm 1
will receive WP 80 mg/m2 for 12 doses followed by standard AC every 21 days for 4 cycles.
Patients in Arm 2 will receive 4 cycles of eribulin 1.4 mg/m2 on days 1 and 8 of a 21-day
cycle followed by standard AC every 21 days for 4 cycles. As soon as possible following
recovery from chemotherapy, the patient will have either lumpectomy or mastectomy and
axillary staging.

In both arms, clinical response will be assessed by physical exam on day 1 of each study
therapy cycle. MRI of the breast is required within 4 weeks prior to randomization and
following completion of eribulin or WP (before starting AC). Following recovery from
surgery, patients will receive radiation therapy and hormonal therapy as clinically
indicated. Other postoperative therapies are prohibited.

Patients will be randomized to the control arm (Arm 1) and to the investigational arm (Arm
2) in a 1:2 ratio. The sample size will be up to 50 patients with about 30 patients in Arm
2 and about half that number in Arm 1. Accrual is expected to occur over 15 months.
Study TypeInterventional
Study PhasePhase 2
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • Breast Cancer
  • HER2-negative Breast Cancer
InterventionDrug: Paclitaxel
80 mg/m2 IV over 60 minutes weekly for 12 weeks
Drug: Eribulin
1.4 mg/m2 IV over 2 to 5 minutes on Days 1 and 8 every 21 days for 4 cycles
Other Names:
eribulin mesylateDrug: Doxorubicin
60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles
Drug: Cyclophosphamide
600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles
Study Arm (s)
  • Active Comparator: Arm 1: Paclitaxel then AC
    Paclitaxel 80 mg/m2 IV weekly for 12 doses followed by doxorubicin and cyclophosphamide IV every 21 days for 4 cycles
  • Experimental: Arm 2: Eribulin then AC
    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

Recruitment Information[ + expand ][ + ]

Recruitment StatusActive, not recruiting
Estimated Enrollment50
Estimated Completion DateFebruary 2015
Estimated Primary Completion DateJune 2014
Eligibility Criteria
Inclusion Criteria:

- 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.

- Patients with alkaline phosphatase > ULN but less than or equal to 1.5 x ULN are
eligible for inclusion in the study if liver imaging (CT, MRI, PET, or PET-CT scan)
performed within 4 weeks prior to randomization does not demonstrate metastatic
disease and the requirements in the criteria below for unexplained skeletal pain are
met.

- Patients with either unexplained skeletal pain or alkaline phosphatase that is > ULN
but less than or equal to 1.5 x ULN are eligible for inclusion in the study if a bone
scan, PET-CT scan, or PET scan performed within 4 weeks prior to randomization does
not demonstrate metastatic disease. Patients with suspicious findings on bone scan
or PET scan are eligible if suspicious findings are determined to be benign by x-ray,
MRI, or biopsy.

- 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).

- ECG performed within 4 weeks before study entry must demonstrate a QTc interval that
is less than or equal to 0.47 seconds.

Exclusion Criteria:

- 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.

- Active infection; or chronic infection requiring chronic suppressive antibiotics.

- Persistent greater than or equal to grade 2 diarrhea regardless of etiology.

- Sensory or motor neuropathy greater than or equal to grade 2, as defined by the NCI
Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0.

- Conditions that would prohibit intermittent administration of corticosteroids for
paclitaxel premedication.

- Chronic daily treatment with corticosteroids with a dose of greater than or equal to
10 mg/day methylprednisolone equivalent (excluding inhaled steroids).

- Uncontrolled hypertension defined as a systolic BP > 150 mmHg or diastolic BP > 90
mmHg, with or without anti-hypertensive medications. (Patients with hypertension
that is well-controlled on medication are eligible.)

- Cardiac disease (history of and/or active disease) that would preclude the use of any
of the drugs included in the treatment regimen. This includes but is not confined
to: Active cardiac disease: symptomatic angina pectoris within the past 180 days
that required the initiation of or increase in anti-anginal medication or other
intervention; ventricular arrhythmias except for benign premature ventricular
contractions; supraventricular and nodal arrhythmias requiring a pacemaker or not
controlled with medication; conduction abnormality requiring a pacemaker; valvular
disease with documented compromise in cardiac function; and symptomatic pericarditis.
History of cardiac disease: myocardial infarction documented by elevated cardiac
enzymes or persistent regional wall abnormalities on assessment of Left Ventricular
(LV) function; history of documented Congestive Heart Failure (CHF) documented
cardiomyopathy; and congenital long QT syndrome.

- Other nonmalignant systemic disease that would preclude the patient from receiving
study treatment or would prevent required follow-up.

- Pregnancy or lactation at the time of randomization.

- Any psychiatric or addictive disorder or other condition that, in the opinion of the
investigator, would preclude her from meeting the study requirements.

- Use of any investigation agent within 4 weeks prior to randomization.
GenderFemale
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States, Canada

Administrative Information[ + expand ][ + ]

NCT Number NCT01705691
Other Study ID NumbersNSABP FB-9
Has Data Monitoring CommitteeNo
Information Provided ByNational Surgical Adjuvant Breast and Bowel Project (NSABP)
Study SponsorNational Surgical Adjuvant Breast and Bowel Project (NSABP)
CollaboratorsEisai Inc.
Investigators Principal Investigator: Norman Wolmark, MD NSABP Foundation, Inc.
Verification DateAugust 2013

Locations[ + expand ][ + ]

CCOP, Colorado Cancer Research Program, Inc.
Denver, Colorado, United States, 80222
CCOP - Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
Phoebe Putney Memorial Hospital
Albany, Georgia, United States, 31703
Memorial Health University Medical Center
Savannah, Georgia, United States, 31404
Henry Ford Health System
Detroit, Michigan, United States, 48202
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007
Providence Hospital - Southfield
Southfield, Michigan, United States, 48075-9975
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901
Carolinas Medical Center/Levine Cancer Center
Charlotte, North Carolina, United States, 28203
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
Albert Einstein Medical Center
Philadelphia, Pennsylvania, United States, 19141
NSABP Foundation, Inc.
Pittsburgh, Pennsylvania, United States, 15212
Allegheny General Hospital/Allegheny-Singer Research Institute
Pittsburgh, Pennsylvania, United States, 15212
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232-1305
Roper Hospital
Charleston, South Carolina, United States, 29401
Cancer Centers of the Carolinas
Greenville, South Carolina, United States, 29615
Joe Arrington Cancer Research & Treatment Center
Lubbock, Texas, United States, 79410
Mary Babb Randolph Cancer Center at West Virginia University Hospitals
Morgantown, West Virginia, United States, 26506
Montreal General Hospital
Montreal, Quebec, Canada, H3G 1A4
Centre Hospitalier de l'Universite de Montreal
Montreal, Quebec, Canada, H2W-1T8