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

NCT01008150 | Completed Phase 2 Results

• 1 other identifier: NSABP FB-7
• Study Type: interventional
• Target: 141
• Locations: 5 countries
• Sites: 42

Brief Summary

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.

Conditions

Breast Cancer

Keywords

breast cancer; neoadjuvant; neratinib; paclitaxel; trastuzumab; doxorubicin; cyclophosphamide

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response in Breast and Axillary Lymph Nodes.

  Number of participants with no histologic evidence of invasive tumor cells in the surgical breast specimen, axillary nodes after neoadjuvant chemotherapy

  At time of surgery, approximately 7 months

Secondary Outcomes (5)

• Pathologic Complete Response in Breast.

  At time of surgery, approximately 7 months

• Clinical Complete Response, as Measured by Physical Exam

  At the completion of AC prior to surgery, approximately 7 months

• Recurrence-free Interval (RFI)

  2 years

• Overall Survival

  24 months

• Adverse Events Experienced by Participants as a Measure of Toxicity

  Assessed through 2 years from randomization

Study Arms (4)

Arm 1: paclitaxel + trastuzumab then A C

ACTIVE COMPARATOR

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)

Drug: Paclitaxel; Drug: Trastuzumab; Drug: Doxorubicin; Drug: Cyclophosphamide

Arm 2: paclitaxel + neratinib then A C

EXPERIMENTAL

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)

Drug: Paclitaxel; Drug: Neratinib; Drug: Doxorubicin; Drug: Cyclophosphamide

Arm 3: paclitaxel + trastuzumab + neratinib then A C

EXPERIMENTAL

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)

Drug: Paclitaxel; Drug: Trastuzumab; Drug: Neratinib; Drug: Doxorubicin; Drug: Cyclophosphamide

Arm 3 NR: paclitaxel+trastuzumab+neratinib

EXPERIMENTAL

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)

Drug: Paclitaxel; Drug: Trastuzumab; Drug: Neratinib; Drug: Doxorubicin; Drug: Cyclophosphamide

Interventions

Paclitaxel DRUG

Also known as: Taxol

Arm 1: paclitaxel + trastuzumab then A C; Arm 2: paclitaxel + neratinib then A C; Arm 3 NR: paclitaxel+trastuzumab+neratinib; Arm 3: paclitaxel + trastuzumab + neratinib then A C

Trastuzumab DRUG

Also known as: Herceptin

Arm 1: paclitaxel + trastuzumab then A C; Arm 3 NR: paclitaxel+trastuzumab+neratinib; Arm 3: paclitaxel + trastuzumab + neratinib then A C

Neratinib DRUG

Arm 2: paclitaxel + neratinib then A C; Arm 3 NR: paclitaxel+trastuzumab+neratinib; Arm 3: paclitaxel + trastuzumab + neratinib then A C

Doxorubicin DRUG

Also known as: Adriamycin, A

Arm 1: paclitaxel + trastuzumab then A C; Arm 2: paclitaxel + neratinib then A C; Arm 3 NR: paclitaxel+trastuzumab+neratinib; Arm 3: paclitaxel + trastuzumab + neratinib then A C

Cyclophosphamide DRUG

Also known as: C

Arm 1: paclitaxel + trastuzumab then A C; Arm 2: paclitaxel + neratinib then A C; Arm 3 NR: paclitaxel+trastuzumab+neratinib; Arm 3: paclitaxel + trastuzumab + neratinib then A C

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.
• 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.
• The Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1.
• Patients must have the ability to swallow oral medication.
• 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.)
• Breast cancer must be determined to be HER2-positive prior to randomization. Assays using FISH or CISH require gene amplification. Assays using IHC require a strongly positive (3+) staining score.
• 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; or 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 greater than 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 2.5 x ULN for the lab; and aspartate aminotransferase (AST) and 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.
• The left ventricular ejection fraction (LVEF) assessment by 2-D echocardiogram or multiple gated acquisition(MUGA) scan performed within 90 days prior to randomization must be greater than or equal to 50% regardless of the facility's LLN.

You may not qualify if:

• 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 SN biopsy for patients with clinically negative axillary nodes.)
• Definitive clinical or radiologic evidence of metastatic disease. (Note: Chest imaging \[mandatory for all patients\] and other imaging \[if required\] must have been performed within 90 days 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 LCIS are eligible.)
• Contralateral invasive breast cancer at any time. (Patients with contralateral DCIS or lobular carcinoma in situ (LCIS) 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, trastuzumab, or neratinib 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.
• 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.

Sponsors & Collaborators

• NSABP Foundation Inc: lead
• Puma Biotechnology, Inc.: collaborator

Study Sites (42)

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Kaiser Permanente-San Diego

San Diego, California, 92120, United States

Location

CCOP - Colorado Cancer Research Program, Inc.

Denver, Colorado, 80224, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Baptist Cancer Institute - Jacksonville

Jacksonville, Florida, 32207, United States

Location

St. Luke's Mountain States Tumor Institute - Boise

Boise, Idaho, 83712, United States

Location

Kootenai Cancer Center

Post Falls, Idaho, 83854, United States

Location

Edward Cancer Center

Naperville, Illinois, 60540, United States

Location

Edward Cancer Center Plainfield

Plainfield, Illinois, 60585, United States

Location

Yorkville Family Practice

Yorkville, Illinois, 60560, United States

Location

St. Vincent Hospital and Health Care Center

Indianapolis, Indiana, 46260, United States

Location

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

Location

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, 55416, United States

Location

University of Missouri-Ellis Fischel

Columbia, Missouri, 65203, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

University Hospital and Medical Center - SUNY Stony Brook

Stony Brook, New York, 11794, United States

Location

CCOP Carolinas HealthCare System

Charlotte, North Carolina, 28232-2861, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Case Western Reserve University/University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

CCOP - Dayton

Dayton, Ohio, 45409, United States

Location

CCOP - Dayton

Kettering, Ohio, 45429, United States

Location

Allegheny Cancer Center at Allegheny General Hospital

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

York Hospital

York, Pennsylvania, 17403, United States

Location

Roper Hosp & Med Asso (Care Alliance Health)

Charleston, South Carolina, 29401, United States

Location

Spartanburg Regional Healthcare System

Spartanburg, South Carolina, 29303, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

West Virginia University Hospitals Inc.

Morgantown, West Virginia, 26506, United States

Location

University of Montreal Hospital Group

Montreal, Quebec, H2W 1T8, Canada

Location

Montreal General Hospital

Montreal, Quebec, H3G 1A4, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Azienda Ospedaliera Fatebenefratelli Milano

Milan, 20121, Italy

Location

MBCCOP - San Juan

San Juan, 00927-5800, Puerto Rico

Location

Galicia Hospital Universitario A Coruña

A Coruña, Galicia, 15006, Spain

Location

Madrid Quiron Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Cataluna Hospital del Mar

Barcelona, 08003, Spain

Location

Cataluna Hospital Quiron de Barcelona

Barcelona, 08023, Spain

Location

Extremadura Hospital San Pedro Alcantara

Cáceres, 10003, Spain

Location

Cataluna Hospital Amau de Vilanova de Lleida

Lleida, 25198, Spain

Location

Valencia Institut Valencia de Oncologia

Valencia, 46009, Spain

Location

Related Publications (2)

• Jacobs SA, Robidoux A, Abraham J, Perez-Garcia JM, La Verde N, Orcutt JM, Cazzaniga ME, Piette F, Antolin S, Aguirre E, Cortes J, Llombart-Cussac A, Di Cosimo S, Kim RS, Feng H, Lipchik C, Lucas PC, Srinivasan A, Wang Y, Song N, Gavin PG, Balousek AD, Paik S, Allegra CJ, Wolmark N, Pogue-Geile KL. NSABP FB-7: a phase II randomized neoadjuvant trial with paclitaxel + trastuzumab and/or neratinib followed by chemotherapy and postoperative trastuzumab in HER2+ breast cancer. Breast Cancer Res. 2019 Dec 3;21(1):133. doi: 10.1186/s13058-019-1196-y.

  PMID: 31796073 DERIVED

• Jankowitz RC, Abraham J, Tan AR, Limentani SA, Tierno MB, Adamson LM, Buyse M, Wolmark N, Jacobs SA. Safety and efficacy of neratinib in combination with weekly paclitaxel and trastuzumab in women with metastatic HER2-positive breast cancer: an NSABP Foundation Research Program phase I study. Cancer Chemother Pharmacol. 2013 Dec;72(6):1205-12. doi: 10.1007/s00280-013-2262-2.

  PMID: 24077916 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; Trastuzumab; neratinib; 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; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; 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: Director, Department of Regulatory Affairs
• Organization: NSABP Foundation, Inc

judy.langer@nsabp.org

412-339-5300

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: November 3, 2009
• First Posted: November 5, 2009
• Study Start: October 1, 2010
• Primary Completion: September 1, 2015
• Study Completion: November 25, 2016
• Last Updated: October 25, 2021
• Results First Posted: December 6, 2018

Record last verified: 2021-10

Locations

IT (1); US (30); CA (3); PR (1); ES (7)