Combination Chemotherapy and Paclitaxel Plus Trastuzumab in Treating Women With Palpable Breast Cancer That Can Be Removed by Surgery
Status: | Completed |
---|---|
Conditions: | Breast Cancer, Cancer, Cancer, Cancer, Cancer |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 1/25/2019 |
Start Date: | July 2007 |
End Date: | February 21, 2013 |
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
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.
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.
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.
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.
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
We found this trial at
115
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Saint Ann's Hospital Located in northeast Columbus, Mount Carmel St. Ann's in Westerville is a...
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Albuquerque, New Mexico 87131
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University of New Mexico Cancer Center It’s been 40 years since the New Mexico State...
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Bronson Methodist Hospital Our healthcare system serves patients and families throughout southwest Michigan and northern...
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West Michigan Cancer Center In 1994, Borgess Health Alliance and Bronson Healthcare Group opened the...
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UMDNJ-New Jersey Medical School NJMS is committed to educating humanistic, culturally competent physicians who will...
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1600 Albany Street
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Beech Grove, Indiana 46107
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Medical University of South Carolina The Medical University of South Carolina (MUSC) has grown from...
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Adena Regional Medical Center Since 1895, Adena Health System has remained focused on its commitment...
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Doctors Hospital Nationally recognized for care quality and patient safety and satisfaction, Doctors Hospital is...
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Riverside Methodist Hospital Serving central Ohio since 1892, Riverside Methodist Hospital is consistently ranked one...
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Columbus CCOP As one of the original 20 CCOPs, the Columbus Community Clinical Oncology Program...
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Miami Valley Hospital Miami Valley Hospital (MVH) is passionate about providing the most recent medical...
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Cancer Center of Kansas, PA - El Dorado Dr. H.E. Hynes founded Cancer Center of...
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Cancer Center of Kansas - Fort Scott Dr. H.E. Hynes founded Cancer Center of Kansas,...
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One Medical Center Drive
Franklin, Ohio 45005
Franklin, Ohio 45005
(513) 424-2111
Atrium Medical Center - Middletown Regional Hospital Atrium Medical Center (Atrium) is built on the...
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Northeast Georgia Medical Center Northeast Georgia Health System (NGHS) is a not-for-profit community health system...
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Wayne Memorial Hospital Wayne Memorial Hospital, an affiliate of Wayne Health Corporation, is home to...
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Wayne Hospital Stretching back to our roots nearly 100 years ago, Wayne HealthCare has always...
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Cancer Center of Kansas-Independence Dr. H.E. Hynes founded Cancer Center of Kansas, P. A. in...
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Borgess Medical Center At Borgess, healing is our calling. This is the place where people...
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Kettering Medical Center Our flagship hospital, Kettering Medical Center, stands proudly in Kettering, Ohio. From...
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University of Tennessee - Knoxville Founded in 1794, we're big on tradition and proud of...
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Fairfield Medical Center We are people you know offering care you trust. Serving more than...
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601 South Rancho Drive
Suite C-26
Las Vegas, Nevada 89106
Las Vegas, Nevada 89106
(702) 384-0013
Nevada Cancer Research Foundation CCOP The Nevada Cancer Research Foundation Community Clinical Oncology Program (NCRF-CCOP)...
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Lawrence Memorial Hospital Lawrence Memorial Hospital (LMH), in collaboration with its medical staff, is dedicated...
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Cancer Center of Kansas, PA - Liberal Dr. H.E. Hynes founded Cancer Center of Kansas,...
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Saint Barnabas Medical Center As a Barnabas Health facility, Saint Barnabas Medical Center is committed...
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Marietta Memorial Hospital We are 2,600 strong and the county
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1660 Springhill Avenue
Mobile, Alabama 36604
Mobile, Alabama 36604
(251) 665-8000
University of South Alabama Mitchell Cancer Institute USA Mitchell Cancer Institute (MCI) is located in...
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Knox Community Hospital A community-owned, 115-bed, not-for-profit hospital located in Mount Vernon, Ohio (approximately 40...
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Licking Memorial Hospital Licking Memorial Health Systems (LMHS) is a not-for-profit health care organization dedicated...
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Cancer Center of Kansas, PA - Newton Dr. H.E. Hynes founded Cancer Center of Kansas,...
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791 Summit Avenue
Oconomowoc, Wisconsin 53066
Oconomowoc, Wisconsin 53066
262-569-9400
Oconomowoc Memorial Hospital-ProHealth Care Inc ProHealth Care is a community-based health care system that offers...
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Singing River Hospital Singing River Health System is a governmental entity organized and existing pursuant...
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Saint Joseph's Regional Medical Center Rich in history, St. Joseph's Healthcare System has evolved from...
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Thomas Jefferson University Hospital Our hospitals in Center City Philadelphia share a 13-acre campus with...
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Southern Ohio Medical Center Southern Ohio Medical Center (SOMC) is a 222-bed 501(C)(3) not-for-profit hospital...
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Cancer Center of Kansas, PA - Pratt Dr. H.E. Hynes founded Cancer Center of Kansas,...
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Reid Hospital & Health Care Services As you will see on campus and throughout our...
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660 S Euclid Ave
Saint Louis, Missouri 63110
Saint Louis, Missouri 63110
(314) 362-5000
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
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Cancer Center of Kansas, PA - Salina Dr. H.E. Hynes founded Cancer Center of Kansas,...
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Swedish Medical Center-First Hill Since 1910, Swedish has been the region's hallmark for excellence in...
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Springfield Regional Medical Center When it comes to your family
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