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
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.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
pCR within the breast, defined as no evidence of invasive tumor remaining in the breast at surgery following completion of chemotherapy
pCR rates will be based on institutional pathology reports. In the final analysis for publication, rates will be based on blinded central review. pCR 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 test will be conducted at the two-sized 0.05 level. A 95% confidence interval will be computed for the difference in pCR rates.
Up to 5 years
No
Aman Buzdar
Principal Investigator
American College of Surgeons
United States: Food and Drug Administration
NCI-2009-00341
NCT00513292
July 2007
Name | Location |
---|---|
Mayo Clinic | Rochester, Minnesota 55905 |
Washington University School of Medicine | Saint Louis, Missouri 63110 |
Medical University of South Carolina | Charleston, South Carolina 29425-0721 |
Bronson Methodist Hospital | Kalamazoo, Michigan 49007 |
West Michigan Cancer Center | Kalamazoo, Michigan 49007-3731 |
Borgess Medical Center | Kalamazooaa, Michigan 49001 |
Waukesha Memorial Hospital | Waukesha, Wisconsin 53188 |
Staten Island University Hospital | Staten Island, New York 10305 |
Broward General Medical Center | Fort Lauderdale, Florida 33316 |
Via Christi Regional Medical Center | Wichita, Kansas 67214 |
Central Baptist Hospital | Lexington, Kentucky 40503 |
Cancer Center of Kansas - Chanute | Chanute, Kansas 66720 |
Cancer Center of Kansas - Dodge City | Dodge City, Kansas 67801 |
Cancer Center of Kansas - Newton | Newton, Kansas 67114 |
Cancer Center of Kansas - Salina | Salina, Kansas 67042 |
Cancer Center of Kansas - Wellington | Wellington, Kansas 67152 |
Associates in Womens Health | Wichita, Kansas 67203 |
Cancer Center of Kansas - Winfield | Winfield, Kansas 67156 |
Adena Regional Medical Center | Chillicothe, Ohio 54601 |
Grady Memorial Hospital | Delaware, Ohio 43015 |
Fairfield Medical Center | Lancaster, Ohio 43130 |
University of South Alabama Mitchell Cancer Institute | Mobile, Alabama 36604 |
University of New Mexico Cancer Center | Albuquerque, New Mexico 87131-5636 |
Parkland Memorial Hospital | Dallas, Texas 75235 |
Saint Rose Hospital | Hayward, California 94545 |
Grandview Hospital | Dayton, Ohio 45405 |
Doctor's Hospital of Laredo | Laredo, Texas 78041 |
Northeast Georgia Medical Center | Gainesville, Georgia 30501 |
Miami Valley Hospital | Dayton, Ohio 45409 |
Cancer Center of Kansas - Fort Scott | Fort Scott, Kansas 66701 |
Cancer Center of Kansas-Independence | Independence, Kansas 67301 |
Lawrence Memorial Hospital | Lawrence, Kansas 66044 |
Mary Rutan Hospital | Bellefontaine, Ohio 43311 |
Wayne Hospital | Greenville, Ohio 45331 |
Knox Community Hospital | Mount Vernon, Ohio 43050 |
Clinton Memorial Hospital | Wilmington, Ohio 45177 |
Morton Plant Hospital | Clearwater, Florida 33756 |
Singing River Hospital | Pascagoula, Mississippi 39581 |
Zale Lipshy University Hospital | Dallas, Texas 75235-7786 |
Greene Memorial Hospital | Xenia, Ohio 45385 |
Lakeland Regional Cancer Center | Lakeland, Florida 33805 |
Riverside Methodist Hospital | Columbus, Ohio 43214 |
Licking Memorial Hospital | Newark, Ohio 43055-2899 |
Columbus CCOP | Columbus, Ohio 43206 |
University of Texas Southwestern Medical Center | Dallas, Texas |
Wichita CCOP | Wichita, Kansas 67214-3882 |
Thomas Jefferson University Hospital | Philadelphia, Pennsylvania 19131 |
M D Anderson Cancer Center | Houston, Texas 77030 |
Eden Hospital Medical Center | Castro Valley, California 94546 |
Valley Medical Oncology Consultants | Pleasanton, California 94588 |
Valley Care Health System - Pleasanton | Pleasanton, California 94588 |
Resurrection Healthcare | Chicago, Illinois 60631 |
Saint Francis Hospital and Health Centers | Beech Grove, Indiana 46107 |
Reid Hospital and Health Care Services | Richmond, Indiana 47374 |
Mercy Medical Center-Sioux City | Sioux City, Iowa 51104 |
Saint Luke's Regional Medical Center | Sioux City, Iowa 51104 |
Cancer Center of Kansas - El Dorado | El Dorado, Kansas 67042 |
Cancer Center of Kansas-Kingman | Kingman, Kansas 67068 |
Cancer Center of Kansas - Parsons | Parsons, Kansas 67357 |
Cancer Center of Kansas - Pratt | Pratt, Kansas 67124 |
Cancer Center of Kansas-Wichita Medical Arts Tower | Wichita, Kansas 67208 |
Cancer Center of Kansas - Main Office | Wichita, Kansas 67214 |
Miller-Dwan Hospital | Duluth, Minnesota 55805 |
Nevada Cancer Research Foundation CCOP | Las Vegas, Nevada 89106 |
Portsmouth Regional Hospital | Portsmouth, New Hampshire 03802 |
Presbyterian Kaseman Hospital | Albuquerque, New Mexico 87110 |
Orange Regional Medical Center | Middletown, New York 10940 |
Doctors Hospital | Columbus, Ohio 43228 |
Grant Medical Center | Columbus, Ohio 43215 |
Mount Carmel Health Center West | Columbus, Ohio 43222 |
Good Samaritan Hospital - Dayton | Dayton, Ohio 45406 |
Dayton CCOP | Dayton, Ohio 45429 |
Samaritan North Health Center | Dayton, Ohio 45415 |
Veteran Affairs Medical Center | Dayton, Ohio 45428 |
Blanchard Valley Hospital | Findlay, Ohio 45840 |
Atrium Medical Center-Middletown Regional Hospital | Franklin, Ohio 45005-1066 |
Kettering Medical Center | Kettering, Ohio 45429 |
Marietta Memorial Hospital | Marietta, Ohio 45750 |
Upper Valley Medical Center | Troy, Ohio 45373 |
Saint Ann's Hospital | Westerville, Ohio 43081 |
Genesis HealthCare System | Zanesville, Ohio 43701 |
Saint Luke's Hospital | Bethlehem, Pennsylvania 18015 |
The Don and Sybil Harrington Cancer Center | Amarillo, Texas 79106 |
Swedish Medical Center-First Hill | Seattle, Washington 98122-4307 |
Oconomowoc Memorial Hospital-ProHealth Care Inc | Oconomowoc, Wisconsin 53066-3896 |
Cancer Center of Kansas-Liberal | Liberal, Kansas 67901 |
UMDNJ - New Jersey Medical School | Newark, New Jersey 07103 |
University of Tennessee - Knoxville | Knoxville, Tennessee 37920 |
Saint Paul Hospital | Dallas, Texas 75235 |
Nashville Breast Center | Nashville, Tennessee 37203 |
Hope, A Women's Cancer Center | Asheville, North Carolina 28816 |
Cancer Centers of Southwest Oklahoma Research | Lawton, Oklahoma |
Saint Francis | Poughkeepsie, New York 12601 |
Southern Ohio Medical Center | Portsmouth, Ohio 45662 |
Gundersen Lutheran | La Crosse, Wisconsin 54601 |
Siouxland Hematology Oncology Associates | Sioux City, Iowa 51101 |
Essentia Health Duluth Clinic CCOP | Duluth, Minnesota 55805 |
Essentia Health Saint Mary's Medical Center | Duluth, Minnesota 55805 |
Springfield Regional Medical Center | Springfield, Ohio 45505 |
The James Graham Brown Cancer Center at University of Louisville | Louisville, Kentucky 40202 |
Marin Cancer Care Inc | Greenbrae, California 94904 |
Covenant Medical Center-Lakeside | Lubbock, Texas 79410 |