Combination Chemotherapy and Paclitaxel Plus Trastuzumab in Treating Women With Palpable Breast Cancer That Can Be Removed by Surgery
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ClinicalTrials.gov Identifier: NCT00513292 |
Recruitment Status :
Completed
First Posted : August 8, 2007
Results First Posted : September 29, 2015
Last Update Posted : January 23, 2019
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Condition or disease | Intervention/treatment | Phase |
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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 (Clinical Trial) |
Actual Enrollment : | 280 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (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 |
Study Start Date : | July 2007 |
Actual Primary Completion Date : | June 2012 |
Actual Study Completion Date : | February 21, 2013 |

Arm | Intervention/treatment |
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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.
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Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Epirubicin Hydrochloride Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Paclitaxel Given IV
Other Names:
Procedure: Therapeutic Conventional Surgery Undergo surgery Biological: Trastuzumab Given IV
Other Names:
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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.
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Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Epirubicin Hydrochloride Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Paclitaxel Given IV
Other Names:
Procedure: Therapeutic Conventional Surgery Undergo surgery Biological: Trastuzumab Given IV
Other Names:
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- 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 ]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.
- 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 ]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 ]The summary of asymptomatic decrease in LVEF.
- Asymptomatic Decreases From Baseline in LVEF at Week 24 [ Time Frame: Baseline, at 24 week ]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 ]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 ]Difference from pretreatment LVEF (%) at 24 weeks [median change from baseline Inter Quartile Range (IQR)].
- Breast Conservation [ Time Frame: From time surgery to up to 5 years ]Surgery was categorized as breast conserving surgery ("Partial Mastectomy") or non-conserving surgery ("Total Mastectomy" or "Modified Radical Mastectomy). Reported below is the percentage of patients receiving "Partial Mastectomy". This was calculated by dividing the number of patients receiving "Partial Mastectomy" by the total number of patients undergoing surgery multiplied by 100 (to obtain the percentage).
- Disease-free Survival (DFS) [ Time Frame: From time to registration to time of event, assessed up to 5 years ]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.
- Overall Survival (OS) [ Time Frame: From time to registration to death, assessed up to 5 years ]OS of Arm I and Arm II patients will be estimated using the Kaplan-Meier method.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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
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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
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Ductal carcinoma in situ (DCIS) or synchronous DCIS of the contralateral breast regardless of prior therapy allowed
- Synchronous invasive breast cancer not allowed
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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
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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
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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
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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
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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
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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
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No prior surgical axillary staging procedure
- Prior non-excisional biopsy of an axillary node allowed
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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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00513292

Principal Investigator: | Aman Buzdar | American College of Surgeons |
Responsible Party: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00513292 |
Other Study ID Numbers: |
NCI-2009-00341 NCI-2009-00341 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CDR0000559039 ACOSOG-Z1041 Z1041 ( Other Identifier: American College of Surgeons Oncology Group ) ACOSOG-Z1041 ( Other Identifier: CTEP ) U10CA012027 ( U.S. NIH Grant/Contract ) |
First Posted: | August 8, 2007 Key Record Dates |
Results First Posted: | September 29, 2015 |
Last Update Posted: | January 23, 2019 |
Last Verified: | January 2019 |
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Paclitaxel Cyclophosphamide Trastuzumab Albumin-Bound Paclitaxel Epirubicin Antineoplastic Agents, Immunological 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 |