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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
80 mg/m2 IV over 60 minutes weekly for 12 weeks
1.4 mg/m2 IV over 2 to 5 minutes on Days 1 and 8 every 21 days for 4 cycles
60 mg/m2 IV over 15 minutes on day 1 every 21 days for 4 cycles
600 mg/m2 IV over 30 minutes on day 1 every 21 days for 4 cycles
CCOP, Colorado Cancer Research Program, Inc.
Denver, Colorado, United States
CCOP - Mount Sinai Medical Center
Miami Beach, Florida, United States
Phoebe Putney Memorial Hospital
Albany, Georgia, United States
Memorial Health University Medical Center
Savannah, Georgia, United States
Henry Ford Health System
Detroit, Michigan, United States
West Michigan Cancer Center
Kalamazoo, Michigan, United States
Providence Hospital - Southfield
Southfield, Michigan, United States
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Carolinas Medical Center/Levine Cancer Center
Charlotte, North Carolina, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
...and 10 more locations
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.
Time frame: At the time of surgery approximately 24 to 28 weeks.
ypCR Nodes
Percentage of patients with no histologic evidence of cancer in axillary lymph nodes.
Time frame: 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)
Percentage of patients with clinical complete response (no significant enhancement on MR images) or clinical partial response (at least 30% decrease in the maximal diameter of the tumor)
Time frame: 12 weeks after initiation of study therapy
Clinical Complete Response (ycCR) Following Neoadjuvant Therapy Assessed by Physical Exam at the Completion of Neoadjuvant Chemotherapy
The number of patients with clinical complete response.
Time frame: 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.
The percentage of patients free from recurrence at 24 months.
Time frame: Assessed through 24 months from randomization
2-year Overall Survival (OS): Death From Any Cause From Time of Randomization Through 2 Years After Randomization.
Percentage of patients alive at 24 months.
Time frame: Assessed through 24 months from randomization
Adverse Events Experienced by Participants as a Measure of Toxicity.
Total patients with at least 1 AE.
Time frame: Assessed through 24 months from randomization
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