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Phase III Randomized Study of Neoadjuvant Combination Chemotherapy Comprising Fluoroucacil, Epirubicin Hydrochloride, and Cyclophosphamide Followed by Paclitaxel and Trastuzumab (Herceptin®) Versus Neoadjuvant
Paclitaxel and Trastuzumab Followed by Combination Chemotherapy Comprising Fluoroucacil, Epirubicin Hydrochloride, Cyclophosphamide and Trastuzumab in Women With Palpable and Operable Breast Cancer
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outcomes Outline Trial Contact Information Registry Information
Alternate Title
Combination Chemotherapy and Paclitaxel Plus Trastuzumab in Treating Women With Palpable Breast Cancer That Can Be Removed by Surgery
Basic Trial Information
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Protocol IDs
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Phase III
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Treatment
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Active
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18 and over
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NCI
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ACOSOG-Z1041 ACOSOG-Z1041, Z1041, NCT00513292
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Special Category:
CTSU trial Objectives Primary - To compare the pathologic complete response rate (pCR) within the breast of patients with breast cancer receiving neoadjuvant combination chemotherapy comprising fluoroucacil, epirubicin hydrochloride, and cyclophosphamide followed by paclitaxel and trastuzumab vs neoadjuvant
paclitaxel with trastuzumab (Herceptin®) followed by combination chemotherapy comprising fluoroucacil, epirubicin hydrochloride, cyclophosphamide, and trastuzumab.
Secondary - To estimate and compare the cardiotoxicity in patients receiving these regimens.
- To compare the combined pCR rate in the breast and ipsilateral axilla obtained with the two regimens evaluated in this study.
- To compare the clinical response rates of the two regimens evaluated in this study.
- To compare the non-cardiac toxicity of the two regimens evaluated in this study.
- To compare breast conservation rates achieved with the two regimens evaluated in this study.
- To evaluate disease-free survival and overall survival at 5 years post-randomization.
- To correlate pCR rate with potential molecular markers of response.
Entry Criteria Disease Characteristics:
- Diagnosis of invasive adenocarcinoma of the breast meeting the following criteria:
- Diagnosed by core needle biopsy (patients with excisional or incisional biopsy of the primary breast tumor are NOT eligible)
- Breast tumor must meet criteria for measurable disease (≥ 2.0 cm) according to RECIST criteria
- 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 prior history of invasive breast cancer
- Hormone receptor status known
Prior/Concurrent Therapy:
- No prior surgical axillary staging procedure
- Prior fine-needle aspiration 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
Patient Characteristics:
- 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
- LVEF ≥ 55.8 by MUGA scan 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
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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
Expected Enrollment 391Outcomes Primary Outcome(s)Pathologic complete response within the breast
Secondary Outcome(s)Combined pathologic complete response rate in the breast and axillary lymph nodes Cardiac event rate during treatment and follow-up LVEF by MUGA at baseline and 3 and 6 months Method of definitive surgery Adverse events by CTCAE version 3.0 Disease-free and overall survival at 5 years
Outline Patients are stratified by tumor size (2.0 - 4.0 cm vs > 4.0 cm), age (< 50 vs ≥ 50) and hormone receptor status (estrogen receptor [ER]- and progesterone receptor [PgR]-negative vs ER- and/or PgR-positive). - Arm I: Patients receive fluoroucacil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. After completion of the fourth course and beginning 21 days later, patients receive paclitaxel IV and trastuzumab (Herceptin®) IV once weekly for 12 weeks. Within 4 weeks after completion of all chemotherapy, patients undergo surgery for tumor. After surgery and beginning 3-4 weeks after the last dose of neoadjuvant trastuzumab, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks.
- Arm II: Patients receive paclitaxel IV once weekly for 12 weeks and trastuzumab IV once weekly for 13 weeks. Beginning 14 days after the last dose of paclitaxel, patients receive 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 4 weeks after completion of all chemotherapy, patients undergo surgery. Beginning 3-4 weeks after the last dose of neoadjuvant trastuzumab, patients receive postoperative trastuzumab as in arm I.
After completion of study therapy, patients are followed every 3 months for 2 years and then every 6 months for 3 years.
Trial Contact Information
Trial Lead Organizations American College of Surgeons Oncology Group | | | Aman Buzdar, MD, Protocol chair | | Ph: 713-792-2817; 800-392-1611 |
| | Kelly Hunt, MD, Protocol co-chair | | | | Trial Sites
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U.S.A. |
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Alabama |
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Mobile |
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| | | | | | | | University of South Alabama Mitchell Cancer Institute |
| | Adam Riker | |
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California |
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Castro Valley |
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| | | East Bay Radiation Oncology Center |
| | James Feusner, MD | |
| | Eden Medical Center |
| | James Feusner, MD | |
| | Valley Medical Oncology Consultants - Castro Valley |
| | James Feusner, MD | |
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Fremont |
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| | Valley Medical Oncology |
| | James Feusner, MD | |
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Oakland |
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| | Alta Bates Summit Medical Center - Summit Campus |
| | Clinical Trials Office - Alta Bates Summit Medical Center - Summit Campus | |
| | Bay Area Breast Surgeons, Incorporated |
| | James Feusner, MD | |
| | CCOP - Bay Area Tumor Institute |
| | James Feusner, MD | |
| | Highland General Hospital |
| | James Feusner, MD | |
| | Larry G Strieff MD Medical Corporation |
| | James Feusner, MD | |
| | Tom K Lee, Incorporated |
| | James Feusner, MD | |
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Pleasanton |
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| | Valley Care Medical Center |
| | James Feusner, MD | |
| | Valley Medical Oncology Consultants - Pleasanton |
| | James Feusner, MD | |
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San Pablo |
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| | Doctors Medical Center - San Pablo Campus |
| | James Feusner, MD | |
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Florida |
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Fort Lauderdale |
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| | | Broward General Medical Center Cancer Center |
| | Clinical Trials Office - Broward General Medical Center Cancer Center | |
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Lakeland |
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| | Lakeland Regional Cancer Center at Lakeland Regional Medical Center |
| | Madhavi Venigalla, MD | Ph: | 863-603-6565 | | 866-823-4405 |
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Georgia |
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Gainesville |
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| | | Northeast Georgia Medical Center |
| | Pierce Dixon, MD | |
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Illinois |
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Evanston |
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| | | Evanston Northwestern Healthcare - Evanston Hospital |
| | Clinical Trials Office - Evanston Northwestern Healthcare - Evanston Hospital | |
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Indiana |
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Beech Grove |
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| | | St. Francis Hospital and Health Centers - Beech Grove Campus |
| | Daniel McKellar, MD | |
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Richmond |
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| | Reid Hospital & Health Care Services |
| | Daniel McKellar, MD | |
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Iowa |
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Sioux City |
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| | | Mercy Medical Center - Sioux City |
| | Donald Wender, MD, PhD | |
| | Siouxland Hematology-Oncology Associates, LLP |
| | Donald Wender, MD, PhD | |
| | St. Luke's Regional Medical Center |
| | Donald Wender, MD, PhD | |
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Minnesota |
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Rochester |
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| | | Mayo Clinic Cancer Center |
| | Clinical Trials Office - All Mayo Clinic Locations | |
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Mississippi |
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Pascagoula |
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| | | Regional Cancer Center at Singing River Hospital |
| | John Bailey | |
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Missouri |
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Saint Louis |
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| | | Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis |
| | Matthew Ellis, MD, PhD, FRCP | Ph: | 314-747-7222 | | 800-600-3606 |
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New Mexico |
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Albuquerque |
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| | | Presbyterian Cancer Treatment Center at Presbyterian Kaseman Hospital |
| | Anne Wallace, MD | |
| | University of New Mexico Cancer Center |
| | Clinical Trials Office - University of New Mexico Cancer Center | |
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North Carolina |
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Asheville |
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| | | Hope A Women's Cancer Center |
| | David Hetzel, MD | |
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Goldsboro |
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| | Wayne Memorial Hospital, Incorporated |
| | James Atkins, MD | |
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Ohio |
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Bellefontaine |
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| | | Mary Rutan Hospital |
| | J. Philip Kuebler, MD, PhD | |
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Chillicothe |
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| | Adena Regional Medical Center |
| | Clinical Trials Office - Adena Regional Medical Center | |
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Columbus |
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| | CCOP - Columbus |
| | J. Philip Kuebler, MD, PhD | |
| | Doctors Hospital at Ohio Health |
| | Clinical Trials Office - Doctors Hospital at Ohio Health | |
| | Grant Medical Center Cancer Care |
| | Clinical Trials Office - Grant Medical Center Cancer Care | |
| | Mount Carmel Health - West Hospital |
| | J. Philip Kuebler, MD, PhD | |
| | Riverside Methodist Hospital Cancer Care |
| | Clinical Trials Office - Riverside Methodist Hospital Cancer Care | |
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Dayton |
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| | CCOP - Dayton |
| | Daniel McKellar, MD | |
| | David L. Rike Cancer Center at Miami Valley Hospital |
| | Clinical Trials Office - David L. Rike Cancer Center at Miami Valley Hospital | |
| | Good Samaritan Hospital |
| | Daniel McKellar, MD | |
| | Grandview Hospital |
| | Daniel McKellar, MD | |
| | Samaritan North Cancer Care Center |
| | Daniel McKellar, MD | |
| | Veterans Affairs Medical Center - Dayton |
| | Daniel McKellar, MD | |
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Delaware |
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| | Grady Memorial Hospital |
| | J. Philip Kuebler, MD, PhD | |
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Findlay |
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| | Blanchard Valley Medical Associates |
| | Daniel McKellar, MD | |
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Franklin |
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| | Middletown Regional Hospital |
| | Daniel McKellar, MD | |
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Kettering |
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| | Charles F. Kettering Memorial Hospital |
| | Clinical Trials Office - Charles F. Kettering Memorial Hospital | Ph: | 937-298-3399 ext. 57556 | | |
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Lancaster |
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| | Fairfield Medical Center |
| | J. Philip Kuebler, MD, PhD | |
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Marietta |
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| | Strecker Cancer Center at Marietta Memorial Hospital |
| | J. Philip Kuebler, MD, PhD | |
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Newark |
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| | Licking Memorial Cancer Care Program at Licking Memorial Hospital |
| | J. Philip Kuebler, MD, PhD | |
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Springfield |
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| | Community Hospital of Springfield and Clark County |
| | J. Philip Kuebler, MD, PhD | |
| | Mercy Medical Center |
| | J. Philip Kuebler, MD, PhD | |
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Troy |
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| | UVMC Cancer Care Center at Upper Valley Medical Center |
| | Clinical Trials Office - UVMC Cancer Care Center at Upper Valley Medical Center | |
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Westerville |
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| | Mount Carmel St. Ann's Cancer Center |
| | J. Philip Kuebler, MD, PhD | |
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Xenia |
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| | Ruth G. McMillan Cancer Center at Greene Memorial Hospital |
| | Daniel McKellar, MD | |
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Zanesville |
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| | Genesis - Good Samaritan Hospital |
| | Clinical Trials Office - Genesis - Good Samaritan Hospital | |
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Pennsylvania |
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Bethlehem |
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| | | St. Luke's Cancer Network at St. Luke's Hospital |
| | Darius Desai, MD | |
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South Carolina |
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Charleston |
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| | | Hollings Cancer Center at Medical University of South Carolina |
| | Clinical Trials Office - Hollings Cancer Center at Medical University of South Carolina | |
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Tennessee |
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Knoxville |
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| | | U.T. Medical Center Cancer Institute |
| | Clinical Trials Office - U.T. Medical Center Cancer Institute | |
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Texas |
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Amarillo |
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| | | Harrington Cancer Center |
| | Clinical Trials Officec - Harrington Cancer Center | |
| Email:
ryokubaitis@harringtoncc.org |
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Dallas |
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| | Parkland Memorial Hospital |
| | Ann Leitch, MD | |
| | Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas |
| | Clinical Trials Office - Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas | Ph: | 866-460-4673; 214-648-7097 | | |
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| | UT Southwestern University Hospital - Zale Lipshy |
| | Ann Leitch, MD | |
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Houston |
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| | M. D. Anderson Cancer Center at University of Texas |
| | Clinical Trials Office - M. D. Anderson Cancer Center at the University of Texas | |
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Laredo |
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| | Doctor's Hospital of Laredo |
| | Gary Unzeitig, MD | |
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Virginia |
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Danville |
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| | | Danville Regional Medical Center |
| | Clinical Trials Office - Danville Regional Medical Center | |
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Newport News |
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| | Surgical Oncology Associates |
| | Richard Hoefer, Jr. | |
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Washington |
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Seattle |
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| | | Swedish Cancer Institute at Swedish Medical Center - First Hill Campus |
| | J. David Beatty, MD | |
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Registry Information | | 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 | | Trial Start Date | | 2007-07-02 | | Trial Completion Date | | 2008-06-01 (estimated) | | Registered in ClinicalTrials.gov | | NCT00513292 | | Date Submitted to PDQ | | 2007-07-02 | | Information Last Verified | | 2008-10-03 | | NCI Grant/Contract Number | | CA12027 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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