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Clinical Trials (PDQ®)

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

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIIBiomarker/Laboratory analysis, TreatmentClosed18 and overNCINCI-2009-00341
CDR0000559039, ACOSOG-Z1041, Z1041, U10CA012027, NCT00513292

Trial Description

Summary

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.

Further Study Information

PRIMARY OBJECTIVES:

I. The primary objective of this study is to compare the pathologic complete response rate (pCR) within the breast of a sequential regimen of concurrent weekly paclitaxel and trastuzumab, followed by continued weekly trastuzumab administered concurrently with FEC-75 (Arm 2), to the pCR rate of a sequential regimen of FEC-75 alone followed by concurrent weekly paclitaxel and trastuzumab (Arm 1).

SECONDARY OBJECTIVES:

I. To estimate the cardiotoxicity of a sequential regimen of concurrent weekly paclitaxel and trastuzumab, followed by continued weekly trastuzumab administered concurrently with FEC-75, followed postoperatively by q 3 week trastuzumab for a total duration of trastuzumab therapy through 52 weeks from the first dose (Arm 2), and compare the cardiotoxicity to that of a sequential regimen of FEC-75 alone followed by concurrent weekly paclitaxel and trastuzumab, followed by q 3 week trastuzumab for a total duration of trastuzumab therapy through 52 weeks from the first dose (Arm 1).

II. To compare the combined pCR rate in the breast and ipsilateral axilla obtained with the two regimens evaluated in this study.

III. To compare the clinical response rates (cRR) of the two regimens evaluated in this study.

IV. To compare the non-cardiac toxicity of the two regimens evaluated in this study.

V. To compare breast conservation rates achieved with the two regimens evaluated in this study.

VI. To evaluate disease-free survival and overall survival at 5 years post-randomization.

VII. To correlate pCR rate with potential molecular markers of response.

OUTLINE: Patients are stratified by clinical tumor size (breast tumor size < 2 cm and nodal metastases < 2 cm vs breast tumor size < 2 cm and nodal metastases ≥ 2 cm vs breast tumor size 2-4 cm [any nodal status] vs breast tumor size ≥ 4 cm [any nodal status]), age (< 50 vs ≥ 50) and hormone receptor status (estrogen receptor [ER]- and progesterone receptor [PgR]-negative vs ER- and/or PgR-positive). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive FEC comprising fluoroucacil intravenously (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.

ARM II: Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after 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.

After completion of study therapy, patients are followed every 3 months for 1 year and then every 6 months for 4 years.

Eligibility 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

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Aman BuzdarPrincipal Investigator

Trial Sites

U.S.A.
Kansas
  Wichita
 Wesley Medical Center
 Shaker R. Dakhil Ph: 316-262-4467
Nevada
  Las Vegas
 Sunrise Hospital and Medical Center
 John Allan Ellerton Ph: 702-731-8274
New Jersey
  Livingston
 St. Barnabas Medical Center Cancer Center
 Richard Alan Michaelson Ph: 973-322-2470
  Paterson
 St. Joseph's Hospital and Medical Center
 Michael Maroules Ph: 973-754-2909
North Carolina
  Goldsboro
 Wayne Memorial Hospital, Incorporated
 James N. Atkins Ph: 919-580-0000
Ohio
  Canton
 Aultman Cancer Center at Aultman Hospital
 Kisa E Weeman Ph: 330-363-6891
Tennessee
  Nashville
 MBCCOP - Meharry Medical College - Nashville
 Steven N. Wolff Ph: 615-327-5724
  Email: jmurray@mmc.edu
Virginia
  Danville
 Danville Regional Medical Center
 Timothy W. Brotherton Ph: 434-793-0044
  Newport News
 Surgical Oncology Associates
 Richard A Hoefer Ph: 757-827-2202

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00513292
ClinicalTrials.gov processed this data on September 25, 2014

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

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