Combination Chemotherapy and Paclitaxel Plus Trastuzumab in Treating Women With Palpable Breast Cancer That Can Be Removed by Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00513292
First received: August 6, 2007
Last updated: June 20, 2016
Last verified: June 2016
  Purpose
This randomized phase III trial is studying giving fluorouracil together with epirubicin and cyclophosphamide followed by paclitaxel and trastuzumab to see how well it works compared with giving paclitaxel together with trastuzumab followed by fluorouracil, epirubicin, cyclophosphamide, and trastuzumab in treating women with palpable breast cancer that can be removed by surgery. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether it is more effective to give combination chemotherapy before or after treatment with paclitaxel plus trastuzumab.

Condition Intervention Phase
HER2/Neu Positive
Stage IA Breast Cancer
Stage IB Breast Cancer
Stage II Breast Cancer
Stage IIIA Breast Cancer
Drug: Cyclophosphamide
Drug: Epirubicin Hydrochloride
Other: Laboratory Biomarker Analysis
Drug: Paclitaxel
Procedure: Therapeutic Conventional Surgery
Biological: Trastuzumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase III Trial Comparing a Neoadjuvant Regimen of FEC-75 Followed by Paclitaxel Plus Trastuzumab With a Neoadjuvant Regimen of Paclitaxel Plus Trastuzumab Followed by FEC-75 Plus Trastuzumab in Patients With HER-2 Positive Operable Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • pCR Within the Breast, Defined as no Evidence of Invasive Tumor Remaining in the Breast at Surgery Following Completion of Chemotherapy [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Pathological complete response (pCR) rates will be based on institutional pathology reports. In the final analysis for publication, rates will be based on blinded central review of these institutional pathology reports. The Chi-squared test will be conducted at the two-sided 0.05 level. A 95% confidence interval will be computed for the difference in pCR rates.


Secondary Outcome Measures:
  • Combined pCR Rate in the Breast and Axillary Lymph Nodes Defined as no Evidence of Invasive Tumor Remaining in Either the Breast or Axillary Nodes at Surgery Following Completion of Chemotherapy [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    pCR Rate in the Breast and Axillary Lymph Nodes Defined as no Evidence of Invasive Tumor Remaining in Either the Breast or Axillary Nodes at Surgery Following Completion of Chemotherapy (among those with Metastasis to movable ipsilateral axillary lymph node(s) (cN1-3) disease).

  • Asymptomatic Decreases From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 12 [ Time Frame: Baseline, at 12 week ] [ Designated as safety issue: No ]
    The summary of asymptomatic decrease in LVEF.

  • Asymptomatic Decreases From Baseline in LVEF at Week 24 [ Time Frame: Baseline, at 24 week ] [ Designated as safety issue: No ]
    The summary of asymptomatic changed in LVEF.

  • LVEFs From Regularly Scheduled Multi Gated Acquisition Scan (MUGA)/Echo Scans as Reported at 12 Week [ Time Frame: At 12 week ] [ Designated as safety issue: No ]
    All patients who had a MUGA or ECHO performed at week 12 are included in the summary of asymptomatic changed in LVEF at week 12. Difference from pretreatment LVEF (%) at 12 weeks [median change from baseline Inter Quartile Range (IQR)].

  • Change in LVEFs (From Regularly Scheduled Multi Gated Acquisition Scan (MUGA)/Echo Scans) From Baseline and at 24 Week [ Time Frame: Baseline, at 24 week ] [ Designated as safety issue: No ]
    Difference from pretreatment LVEF (%) at 24 weeks [median change from baseline Inter Quartile Range (IQR)].

  • Breast Conservation Rates [ Time Frame: From time surgery to up to 5 years ] [ Designated as safety issue: No ]
    Method of definitive surgery, categorized as breast conserving surgery ("lumpectomy") or total mastectomy. Breast conservation rates will be compared using the Mantel-Haenszel test, stratified by tumor size (2.0 -4.0 cm, > 4.0 cm), age (< 50, >= 50) and hormone receptor status (ER- and PgR-negative, ER- and/or PgR positive). The Chi-squared will be conducted at the two-sided .05 level. A 95% confidence interval will be computed for the difference in breast conservation rates.

  • Disease-free Survival (DFS) [ Time Frame: From time to registration to time of event, assessed up to 5 years ] [ Designated as safety issue: No ]
    DFS defined as inoperable progressive disease, gross residual disease following definitive surgery, local, regional or distant recurrence, contralateral breast cancer, other second primary cancers, and death prior to recurrence or second primary cancer. DFS of Arm I and Arm II patients will be estimated using the Kaplan-Meier method. The difference will be tested using the log-rank test, stratified by tumor size (2.0 - 4.0 cm, > 4.0 cm), age (< 50, >= 50), and hormone receptor status (ER- and PgR-negative, ER- and/or PgR-positive).

  • Overall Survival (OS) [ Time Frame: From time to registration to death, assessed up to 5 years ] [ Designated as safety issue: No ]
    OS of Arm I and Arm II patients will be estimated using the Kaplan-Meier method. The difference will be tested using the log-rank test, stratified by tumor size (2.0 - 4.0 cm, > 4.0 cm), age (< 50, >= 50), and hormone receptor status (ER- and PgR-negative, ER- and/or PgR-positive).


Enrollment: 280
Study Start Date: July 2007
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: FEC-75 then Paclitaxel/trastuzumab
Patients receive FEC comprising fluoroucacil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks.
Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Epirubicin Hydrochloride
Given IV
Other Names:
  • Ellence
  • IMI-28
  • Pharmorubicin PFS
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat
Procedure: Therapeutic Conventional Surgery
Undergo surgery
Biological: Trastuzumab
Given IV
Other Names:
  • ABP 980
  • Anti-c-ERB-2
  • Anti-c-erbB2 Monoclonal Antibody
  • Anti-ERB-2
  • Anti-erbB-2
  • Anti-erbB2 Monoclonal Antibody
  • Anti-HER2/c-erbB2 Monoclonal Antibody
  • Anti-p185-HER2
  • c-erb-2 Monoclonal Antibody
  • HER2 Monoclonal Antibody
  • Herceptin
  • Herceptin Biosimilar PF-05280014
  • Herceptin Trastuzumab Biosimilar PF-05280014
  • MoAb HER2
  • Monoclonal Antibody c-erb-2
  • Monoclonal Antibody HER2
  • PF-05280014
  • rhuMAb HER2
  • Trastuzumab Biosimilar ABP 980
  • Trastuzumab Biosimilar PF-05280014
Experimental: Paclitaxel/trastuzumab then trastuzumab/FEC-75
Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluoroucacil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I.
Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Epirubicin Hydrochloride
Given IV
Other Names:
  • Ellence
  • IMI-28
  • Pharmorubicin PFS
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat
Procedure: Therapeutic Conventional Surgery
Undergo surgery
Biological: Trastuzumab
Given IV
Other Names:
  • ABP 980
  • Anti-c-ERB-2
  • Anti-c-erbB2 Monoclonal Antibody
  • Anti-ERB-2
  • Anti-erbB-2
  • Anti-erbB2 Monoclonal Antibody
  • Anti-HER2/c-erbB2 Monoclonal Antibody
  • Anti-p185-HER2
  • c-erb-2 Monoclonal Antibody
  • HER2 Monoclonal Antibody
  • Herceptin
  • Herceptin Biosimilar PF-05280014
  • Herceptin Trastuzumab Biosimilar PF-05280014
  • MoAb HER2
  • Monoclonal Antibody c-erb-2
  • Monoclonal Antibody HER2
  • PF-05280014
  • rhuMAb HER2
  • Trastuzumab Biosimilar ABP 980
  • Trastuzumab Biosimilar PF-05280014

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of invasive adenocarcinoma by core needle biopsy

    • Fine needle aspiration allowed provided primary tumor size < 2 cm and lymph node metastases are present
    • Excisional biopsy of the primary tumor allowed provided biopsy-positive lymph nodes are present
  • Primary tumor ≥ 2 cm and/or ≥ 1 biopsy-positive lymph node
  • HER2-positive disease

    • Confirmation by fluorescent in situ hybridization (FISH) requires gene amplification
    • Confirmation by immunohistochemistry (IHC) requires a strongly positive (3+) staining intensity score
  • Ductal carcinoma in situ (DCIS) or synchronous DCIS of the contralateral breast regardless of prior therapy allowed

    • Synchronous invasive breast cancer not allowed
  • Ipsilateral DCIS treated by local excision with or without hormonal therapy allowed

    • Those treated with radiation therapy are not allowed
  • No definitive clinical or radiologic evidence of metastatic disease
  • No history of invasive breast cancer
  • Hormone receptor status known
  • Menopausal status not specified
  • ECOG performance status of 0 -1
  • Absolute neutrophil count ≥ 1,200/mm³
  • Platelet count ≥ 100,000/mm³
  • Total bilirubin normal unless the patient has a grade 1 bilirubin elevation (normal to 1.5 times upper limit of normal [ULN]) resulting from Gilbert disease or similar syndrome due to slow conjugation of bilirubin
  • Alkaline phosphatase ≤ 2.5 times ULN
  • AST ≤ 1.5 times ULN
  • Creatinine normal
  • Left ventricular ejection fraction (LVEF) ≥ 55 by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) within the past 3 months
  • Patients with either skeletal pain or alkaline phosphatase that is > ULN but ≤ 2.5 times ULN allowed if bone scans fail to demonstrate metastatic disease

    • Suspicious findings on bone scan must be confirmed as benign by x-ray, MRI, or biopsy
  • Prior non-breast malignancies allowed if disease-free for 5 years since completion of initial treatment regimen and deemed by their physician to be at low risk for recurrence

    • Patients who had the following cancers are eligible if diagnosed and treated within the past 5 years:

      • Carcinoma in situ of the cervix
      • Colon carcinoma in situ
      • Melanoma in situ
      • Basal cell and squamous cell carcinoma of the skin
  • No cardiac disease that would preclude the use of epirubicin hydrochloride or trastuzumab (Herceptin®) including any of the following:

    • Active cardiac disease
    • Angina pectoris that requires the use of antianginal medication
    • Cardiac arrhythmia requiring medication
    • Severe conduction abnormality
    • Clinically significant valvular disease
    • Cardiomegaly on chest x-ray
    • Ventricular hypertrophy on EKG
    • Patient's with poorly controlled hypertension ( i.e., diastolic greater than 100 mm/Hg)

      • Patients with hypertension that is well controlled on medication are eligible
    • History of cardiac disease
    • Myocardial infarction documented as a clinical diagnosis or by EKG or any other tests
    • Documented congestive heart failure
    • Documented cardiomyopathy
  • No sensory or motor neuropathy ≥ grade 2, as defined by the NCI's CTCAE v3.0
  • Women of reproductive potential must agree to use an effective non-hormonal method of contraception during therapy
  • Women of child bearing potential must have a negative urine or serum pregnancy test within 2 weeks of registration
  • Not pregnant or nursing
  • No psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements
  • No non-malignant systemic disease (e.g., cardiovascular, renal, hepatic) that would preclude treatment with either of the treatment regimens
  • No prior surgical axillary staging procedure

    • Prior non-excisional biopsy of an axillary node allowed
  • No prior treatment for this breast cancer

    • Hormonal therapy allowed if had been given for up to a total of 28 days anytime after diagnosis and before study entry
    • Hormonal therapy must stop at or before study entry and be re-started, if indicated, following surgery
  • No prior therapy with anthracyclines or taxanes for any malignancy
  • No other investigational agents within the past 30 days
  • No concurrent sex hormonal therapy (e.g., birth control pills, ovarian hormonal replacement therapy)
  • No concurrent therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulator (SERM), either for osteoporosis or breast cancer prevention
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00513292

  Show 115 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Aman Buzdar American College of Surgeons
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00513292     History of Changes
Other Study ID Numbers: NCI-2009-00341  NCI-2009-00341  CDR0000559039  ACOSOG-Z1041  Z1041  ACOSOG-Z1041  U10CA012027 
Study First Received: August 6, 2007
Results First Received: July 14, 2015
Last Updated: June 20, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Cyclophosphamide
Trastuzumab
Epirubicin
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 23, 2016