Phase II Randomized Trial Evaluating Neoadjuvant Therapy With Neratinib and/or Trastuzumab Followed by Postoperative Trastuzumab in Women With Locally Advanced HER2-positive Breast Cancer

Recruiting in Palo Alto (17 mi)

+41 other locations

Overseen byNorman Wolmark, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: NSABP Foundation Inc

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

FB-7 is a Phase II, multi-center randomized study of neratinib in combination with weekly paclitaxel with or without trastuzumab followed by doxorubicin and cyclophosphamide (AC) as neoadjuvant therapy for women with HER2-positive locally advanced breast cancer. Patients in the control arm will receive neoadjuvant trastuzumab in combination with weekly paclitaxel followed by AC. The primary aim of the study is to determine the pathologic complete response (pCR) rate in breast and axillary nodes following the neoadjuvant therapy regimens. The secondary aims include determination of the pCR rate in breast only, clinical complete response (cCR) rate, two-year recurrence-free interval, two-year overall survival, toxicity of the neoadjuvant regimens, and exploration of molecular and genetic correlates of response.

Research Team

Norman Wolmark, MD

Principal Investigator

NSABP Foundation Inc

Eligibility Criteria

Inclusion Criteria

Patients should have a life expectancy of at least 10 years, excluding their diagnosis of breast cancer.

Submission of a block from the diagnostic biopsy sample and from the surgical sample, if gross residual disease greater than or equal to 1.0 cm was removed at the time of surgery, is required for all patients

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.

See 7 more

Treatment Details

Interventions

Cyclophosphamide (Alkylating agents)
Doxorubicin (Anthracycline)
Neratinib (Tyrosine Kinase Inhibitor)
Paclitaxel (Taxane)
Trastuzumab (Monoclonal Antibodies)

Participant Groups

4Treatment groups

Experimental Treatment

Active Control

Group I: Arm 3: paclitaxel + trastuzumab + neratinib then A CExperimental Treatment5 Interventions

4 cycles of paclitaxel 80 mg/m2 on days 1, 8, and 15 of a 28 day cycle. Trastuzumab concurrently with paclitaxel, weekly for a total of 16 doses (4 mg/kg loading dose, then 2 mg/kg weekly). Neratinib 200 mg orally once daily beginning on Day 1 of paclitaxel and continuing through Day 28 of the final cycle of paclitaxel. Following paclitaxel/trastuzumab/neratinib therapy, standard AC every 21 days for 4 cycles. Following surgery, trastuzumab (8 mg/kg loading dose, then 6 mg/kg) every 3 weeks to complete 1 year of targeted therapy (either preoperative trastuzumab therapy or neratinib therapy)

Group II: Arm 3 NR: paclitaxel+trastuzumab+neratinibExperimental Treatment5 Interventions

Non-randomized: 4 cycles of paclitaxel 80 mg/m2 on days 1, 8, and 15 of a 28 day cycle. Trastuzumab concurrently with paclitaxel, weekly for a total of 16 doses (4 mg/kg loading dose, then 2 mg/kg weekly). Neratinib 200 mg orally once daily beginning on Day 1 of paclitaxel and continuing through Day 28 of the final cycle of paclitaxel. Following paclitaxel/trastuzumab/neratinib therapy, standard AC every 21 days for 4 cycles. Following surgery, trastuzumab (8 mg/kg loading dose, then 6 mg/kg) every 3 weeks to complete 1 year of targeted therapy (either preoperative trastuzumab therapy or neratinib therapy)

Group III: Arm 2: paclitaxel + neratinib then A CExperimental Treatment4 Interventions

4 cycles of paclitaxel 80 mg/m2 on Days 1, 8, and 15 of a 28-day cycle. Neratinib 240 mg orally once daily beginning on Day 1 of paclitaxel and continuing through Day 28 of the final cycle of paclitaxel. Following paclitaxel/neratinib therapy, standard AC every 21 days for 4 cycles. Following surgery, trastuzumab (8 mg/kg loading dose, then 6 mg/kg) every 3 weeks to complete 1 year of targeted therapy (either preoperative trastuzumab therapy or neratinib therapy)

Group IV: Arm 1: paclitaxel + trastuzumab then A CActive Control4 Interventions

4 cycles of paclitaxel 80 mg/m2 on Days 1, 8, and 15 of a 28-day cycle. Trastuzumab concurrently with paclitaxel weekly for a total of 16 doses (4 mg/kg loading dose, then 2 mg/kg weekly). Following paclitaxel/trastuzumab, standard AC every 21 days for 4 cycles. Following surgery, trastuzumab (8 mg/kg loading dose, then 6 mg/kg) every 3 weeks to complete 1 year of targeted therapy (either preoperative trastuzumab therapy or neratinib therapy)

Cyclophosphamide is already approved in Canada, Japan for the following indications: