Therapy With Abraxane and 5-Fluorouracil, Epirubicin, Cyclophosphamide (FEC) for Patients With Breast Cancer - Full Text View

Sponsors and Collaborators:	National Surgical Adjuvant Breast and Bowel Project (NSABP) Abraxis BioScience Inc.
Information provided by:	National Surgical Adjuvant Breast and Bowel Project (NSABP)
ClinicalTrials.gov Identifier:	NCT00110695

Purpose

The purpose of this study is to learn how breast cancer tumors respond to a drug called Abraxane followed by a combination of 3 chemotherapy drugs commonly used for breast cancer.

Condition	Intervention	Phase
Breast Neoplasms	Drug: Nanoparticle albumin bound paclitaxel followed by FEC	Phase II

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Cyclophosphamide Paclitaxel Fluorouracil Epirubicin hydrochloride Epirubicin Trastuzumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase 2 Study of Neoadjuvant Chemotherapy With Sequential Weekly Nanoparticle Albumin Bound Paclitaxel (Abraxane) Followed by 5-Fluorouracil, Epirubicin, Cyclophosphamide (FEC) in Locally Advanced Breast Cancer

Further study details as provided by National Surgical Adjuvant Breast and Bowel Project (NSABP):

Primary Outcome Measures:

pathologic complete response rate in the breast for patients with locally advanced breast cancer (LABC) who receive Abraxane [ Time Frame: pCR examined in breast tissue taken at surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

pathologic complete response rate in the breast and axillary nodes (pCR breast and nodes) in all patients [ Time Frame: pCR examined in breast and lymph node tissue taken at surgery ] [ Designated as safety issue: No ]
complete clinical response rate (cCR) of the sequential regimen in patients who present with palpable measurable disease [ Time Frame: physical exam between the two chemotherapy regimens and at completion of the entire treatment regimen ] [ Designated as safety issue: No ]
complete clinical and imaging response rate (ciCR) of the sequential regimen in all patients [ Time Frame: physical exam and breast imaging at 3-4 weeks after the last chemotherapy treatment ] [ Designated as safety issue: No ]
complete clinical response rate (cCR)of Abraxane in patients who present with palpable measurable disease [ Time Frame: physical exam at completion of the Abraxane portion of the treatment regimen ] [ Designated as safety issue: No ]
toxicity of the sequential chemotherapy regimen [ Time Frame: during treatment and for 3 to 4 weeks after the last chemotherapy cycle ] [ Designated as safety issue: Yes ]
toxicity of the sequential chemotherapy regimen when administered concurrently with trastuzumab [ Time Frame: during treatment and for 3 to 4 weeks after the last chemotherapy cycle ] [ Designated as safety issue: Yes ]
2-year progression-free survival [ Time Frame: from the first dose of study therapy to first date of disease progression or for a maximum of 24 months from study entry ] [ Designated as safety issue: No ]
2-year overall survival (OS) [ Time Frame: from the first dose of study therapy to date of death or for a maximum of 24 months from study entry ] [ Designated as safety issue: No ]
exploration of molecular and genetic correlates of response [ Time Frame: after specimen procurement and continuing after completion of clinical phase of study ] [ Designated as safety issue: No ]

Enrollment:	66
Study Start Date:	April 2005
Study Completion Date:	July 2008
Primary Completion Date:	December 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental	Drug: Nanoparticle albumin bound paclitaxel followed by FEC Nanoparticle albumin bound paclitaxel 100 mg/m2 IV for 30 minutes once weekly for 12 weeks followed by FEC (5-FU 500mg/m2 IV push; epirubicin 100 mg/m2 IV over 15 min. [or if given with trastuzumab 75 mg/m2 IV over 15 min.]; cyclophosphamide 500 mg/m2 IV over 30 min.) on Day 1 every 21 days

Detailed Description:

This is a Phase 2, non-randomized study of neoadjuvant treatment with nanoparticle albumin bound paclitaxel (Abraxane) every week for 12 weeks followed by 5-FU, epirubicin, and cyclophosphamide (FEC) every 3 weeks for 4 cycles in women with locally advanced breast cancer. Patients with HER-2 overexpressing breast cancer may receive trastuzumab concurrently with the chemotherapy at the discretion of the investigator. The primary aim of this study is to determine the pathologic complete response rate (pCR) of this sequential regimen.

Patients who achieve clinical complete response (cCR), clinical partial response (cPR), or have resectable stable disease (SD) will undergo surgery. Surgery will consist of modified radical mastectomy or excision of the primary tumor site with clear surgical margins accompanied by axillary staging. Tumor samples taken prior to initiation of treatment will be analyzed for molecular and genetic changes which will be correlated with tumor response.

Patients must have a histologically confirmed diagnosis of breast cancer without documented evidence of distant metastatic disease. Patients with clinical Stage IIB (T3N0 only), IIIA, or IIIB breast cancer will be potential candidates for this trial.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Signed consent
Diagnosis made by core biopsy or incisional biopsy
Histologic confirmation of invasive breast cancer
Clinical staging as IIB (cT3N0 only), IIIA (cT3N1 or cT0-3N2), or IIIB (cT4N0-2)
ECOG performance 0 or 1
At the time of entry: *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; *serum creatinine must be less than or equal to ULN for the lab.
The following criteria for evidence of adequate hepatic function must be met: *Total bilirubin must be less than or equal to ULN for the lab unless the patient has a grade 1 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 < 2.5 x ULN for the lab; and

*AST must be less than or equal to 1.5 x ULN for the lab.
MUGA scan or echocardiogram within 3 months prior to entry if: *age greater than or equal to 60, or *history of hypertension, or *plan to receive trastuzumab. For any patient who has a MUGA scan or echocardiogram performed for any reason, the baseline LVEF must be greater than or equal to LLN for the facility performing the procedure and there must be no regional wall abnormalities

Exclusion Criteria:

Clinical stage IIB disease that is cT2N1.
Definitive evidence of metastatic disease (M1 by AJCC criteria)
Prior history of invasive breast cancer in either breast or ductal carcinoma in situ (DCIS) in the ipsilateral breast treated with radiation therapy (patients with a history of lobular carcinoma in situ [LCIS] are eligible).
Any treatment for the currently diagnosed breast cancer prior to study entry including radiation therapy, chemotherapy, and/or hormonal therapy.
Pregnancy or lactation at the time of study entry.
Prior anthracycline or taxane-containing chemotherapy for any malignancy.
Nonmalignant systemic disease (cardiovascular, renal, hepatic, diabetes, etc.) that would preclude the patient from receiving study treatment or would prevent required follow-up.
Grade 2 or greater peripheral polyneuropathy at the time of entry.
Cardiac disease that would preclude the use of anthracyclines or trastuzumab. This includes:

*myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LV function; *angina pectoris that requires the use of anti-anginal medication; *any history of documented congestive heart failure; *serious cardiac arrhythmia requiring medication; *severe conduction abnormality; *valvular disease with documented cardiac function compromise; or *uncontrolled hypertension defined as blood pressure > 160/100 mm/Hg.
Any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement therapy, etc. (These patients are eligible if this therapy is discontinued prior to randomization.) Women of reproductive potential must agree to use an effective non-hormonal method of contraception during therapy.
Therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulator (SERM), either for osteoporosis or breast cancer prevention. Patients are eligible only if these medications are discontinued prior to randomization.
Use of any investigational agent within the month before enrollment in the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00110695

Locations

United States, Pennsylvania
NSABP Operations Center
Pittsburgh, Pennsylvania, United States, 15212

Sponsors and Collaborators

National Surgical Adjuvant Breast and Bowel Project (NSABP)

Abraxis BioScience Inc.

Investigators

Principal Investigator:

Norman Wolmark, MD

NSABP Foundation, Inc.

More Information

Publications:

Robidoux A, Buyse M, Buzdar A, et al.: Neoadjuvant chemotherapy with sequential weekly nanoparticle albumin-bound paclitaxel (ABI-007, Abraxane®) followed by 5-fluorouracil, epirubicin and cyclophosphamide (FEC) in locally advanced breast cancer (LABC): a phase II trial of the NSABP Foundation research program (FRP). [Abstract] Annual San Antonio Breast Cancer Symposium 3068, 2006.

Responsible Party:	NSABP Foundation, Inc. ( Norman Wolmark, MD )
Study ID Numbers:	NSABP FB-AX-003
Study First Received:	May 12, 2005
Last Updated:	August 11, 2008
ClinicalTrials.gov Identifier:	NCT00110695
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board; Canada: Health Canada; Health Products & Food Branch; Canada: Institutional Review Boards

Keywords provided by National Surgical Adjuvant Breast and Bowel Project (NSABP):

NSABP
Abraxis
Abraxane
Locally advanced breast cancer

Fluorouracil
Epirubicin
Cyclophosphamide
FEC

Study placed in the following topic categories:

Skin Diseases
Paclitaxel
Fluorouracil
Trastuzumab

Breast Neoplasms
Cyclophosphamide
Epirubicin
Breast Diseases

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Mitosis Modulators
Physiological Effects of Drugs
Antimitotic Agents
Antibiotics, Antineoplastic
Immunosuppressive Agents

Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009