TAC Versus TC for Adjuvant Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT00493870
- Lead Sponsor
- US Oncology Research
- Brief Summary
The purpose of this research study is to find out what effects (good and bad) TC or TAC has on early stage HER2- breast cancer.
- Detailed Description
Both TAC (docetaxel, doxorubicin, and cyclophosphamide) and TC (docetaxel and cyclophosphamide) are established adjuvant chemotherapy regimens for early stage breast cancer. TAC, however, due to the inclusion of the anthracycline doxorubicin, carries a high risk of hematologic and cardiotoxic adverse effects. Substantial evidence supports the concept that early stage HER2-negative breast cancers will benefit similarly from anthracycline-based adjuvant and non-anthracycline-based chemotherapy.
Further, approximately 0 to 9% of HER2-negative breast cancers have alterations in the TOP2A gene, which may predict for benefit from anthracycline-based chemotherapy.
We hypothesize that 6 cycles of TC versus 6 cycles of TAC will have similar efficacy in the treatment of early stage HER2-negative breast cancer and that TC will have less toxicity. If this hypothesis were upheld and the anthracycline doxorubicin could be eliminated from the regimen while obtaining similar efficacy in this population of patients, it would not only be an important advance in the understanding of the biology of cancer, but it would also be of significant clinical benefit to women with breast cancer.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 1961
A woman will be eligible for inclusion in this study if she meets all of the following criteria:
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Age >18 to <70 years old.
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Has known ER and PR status
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Has HER2 nonamplified disease, confirmed by FISH
-
Has known menopausal status (see Section 7.3 for criteria)
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Has operable, histologically confirmed, Stage I, IIA, IIB, or IIIA, IIIB, or IIIC invasive carcinoma of the breast. Bilateral synchronous breast cancer is allowable provided that 1 primary meets the inclusion criteria.
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Meets 1 of the 3 following criteria:
- T1-3N1-3M0 if ER positive or negative
- T2-3N0M0 if ER positive or negative
- T1N0M0 if ER and PR negative
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Has complete surgical resection of the primary breast tumor: either lumpectomy or mastectomy with sentinel lymph node biopsy or axillary dissection, with clear margins for both invasive and ductal carcinoma in situ (DCIS)
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Has had no prior chemotherapy unless >5 years ago
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Has an ECOG Performance Status (PS) 0-1
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Has laboratory values of: See protocol for specific details
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Has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and alkaline phosphatase (ALP) within the ranges shown below. In determining eligibility the more abnormal of the 2 values (AST or ALT) should be used. See protocol for specific details
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Has normal cardiac function as evidenced by a LVEF >50%, but WNL by institutional standard by multiple gated acquisition (MUGA) scan. An echocardiogram (ECHO) may be used if MUGA is not available, but the same modality must be used consistently throughout the study to evaluate LVEF. Ejection fraction as determined by ECHO must be WNL by institutional standard.
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Has no evidence of metastatic disease outside of breast by physical examination and chest x-ray. Other scans if done as needed by the patient (eg, bone scan; abdominal, chest CT; PET or PET/CT; ultrasound; or MRI should indicate no evidence of metastatic disease
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Has had baseline bilateral mammography
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It has been <84 days since the date of definitive surgery (eg, mastectomy or, in the case of a breast-sparing procedure, axillary dissection) with adequate wound healing, as determined by the Treating Physician
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Has a negative serum pregnancy test within 7 calendar days prior to registration (female patients of childbearing potential [not surgically sterilized and between menarche and 1 year postmenopause])
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If fertile, patient has agreed to use an acceptable method of birth control (barrier contraceptive only) to avoid pregnancy for the duration of the study and for a period of 3 months thereafter
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Has adequate tumor specimen available for FISH analysis of TOP2A status (See Appendix VI).
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Has signed a Patient Informed Consent Form
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Has signed a Patient Authorization Form
A woman will be excluded from this study if she meets any of the following criteria:
- Has any evidence of metastatic disease following surgical resection of the primary tumor including: positive surgical margins, staging work-up, or physical examination suspicious for malignant disease
- Has T4 disease (ie, patients with fixed tumors, peau d'orange skin changes, skin ulcerations, or inflammatory changes)
- Has Stage IV breast cancer (M1 disease on TNM staging system)
- Has a history of severe hypersensitivity reaction to drugs formulated with polysorbate 80
- Has had neoadjuvant chemotherapy for this breast cancer
- Has ever had a myocardial infarction (MI) or has a history of heart failure, uncontrolled angina, severe uncontrolled arrhythmias, pericardial disease, or electrocardiographic evidence of acute ischemic changes
- Is receiving concurrent immunotherapy, hormonal therapy (eg, tamoxifen, hormone replacement therapy), or radiation therapy. Must discontinue prior to registering on the study.
- Is receiving concurrent investigational therapy or has received such therapy within the past 30 calendar days
- Has peripheral neuropathy >Grade 1
- Has had a major organ allograft or condition requiring chronic immunosuppression (ie, kidney, liver, lung, heart, bone marrow transplant, or autoimmune diseases). Patients who have received corneal transplants or cadaver skin or bone transplants are eligible.
- Has a serious uncontrolled intercurrent medical or psychiatric illness, including serious viral (including clinically defined AIDS), bacterial or fungal infection; or history of uncontrolled seizures, or diabetes, or CNS disorders deemed by the Treating Physician to be clinically significant, precluding informed consent
- Has active hepatitis B or hepatitis C with abnormal liver function tests (LFTs) or is known to be HIV positive
- Has a history of other malignancy within the last 5 years (except cured basal cell carcinoma of skin, carcinoma in situ of uterine cervix, DCIS, which could affect the diagnosis or assessment of any of the study drugs
- In an obese patient to whom the Treating Physician would not be comfortable administering full doses of study drugs as calculated by the BSA. Obese patients will be treated based on actual body weight. Obese patients treated with full doses based on actual BSA are eligible.
- Is pregnant or breastfeeding
- Is deemed unable to comply with requirements of study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TAC Docetaxel doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 and docetaxel 75 mg/m2 TAC Doxorubicin doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 and docetaxel 75 mg/m2 TC Docetaxel docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 TAC Cyclophosphamide doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 and docetaxel 75 mg/m2 TC Cyclophosphamide docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2
- Primary Outcome Measures
Name Time Method 3-year Invasive Disease-free Survival (IDFS) Among Analyzed ITT Patients 3 years from randomization into study The primary objective of the study is to compare the 3-year invasive disease-free survival (IDFS) of adjuvant TC versus TAC as treatment for early stage HER2-negative breast cancer among analyzed ITT patients. ITT patients are all patients who were randomized, whether or not they followed protocol. IDFS, defined as the time from the date of randomization to local recurrence following mastectomy, invasive local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, invasive contralateral breast cancer, second primary cancer (other than squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, colorectal carcinoma in situ, or lobular carcinoma in situ of the breast), or death from any cause prior to recurrence or second primary cancer. Patients who have not had any such event at the time of data analysis will be censored at the last date they were known to be event-free.
3-year Invasive Disease-free Survival (IDFS) Among Per-protocol Patients 3 years from randomization into study The primary objective of the study is to compare the 3-year invasive disease-free survival (IDFS) of adjuvant TC versus TAC as treatment for early stage HER2-negative breast cancer among per-protocol patients. Per-protocol only includes those patients who were randomized and received treatment as outlined in the protocol.
- Secondary Outcome Measures
Name Time Method 3-year DFS-DCIS, OS and RFI Among Analyzed ITT Patients 3 years from randomization into study To compare disease-free survival-ductal carcinoma in situ (DFS-DCIS),overall survival (OS) and recurrence free interval (RFI) of TC with TAC. DFS-DCIS, defined as the time from the date of randomization to local recurrence following mastectomy, local recurrence in the ipsilateral breast following lumpectomy (invasive or non-invasive), regional recurrence, distant recurrence, contralateral breast cancer (invasive or non-invasive), second primary cancer (other than squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, colorectal carcinoma in situ, or lobular carcinoma in situ of the breast), or death from any cause prior to recurrence or second primary cancer. Patients who have not had any such event at the time of data analysis will be censored at the last date they were known to be event-free.
3-year DFS-DCIS, OS and RFI Among Per-protocol Patients. 3 years from randomization into study To compare disease-free survival-ductal carcinoma in situ (DFS-DCIS),overall survival (OS) and recurrence free interval (RFI) of TC with TAC among per protocol patients.
Number and Frequency of Participants by TOP2A Status by Study Treatment 10 years (from baseline to end of study participation) To evaluate the effectiveness of TC and TAC in TOP2A altered (amplified, deleted, or overexpressed at the protein level) early stage HER2-negative breast cancer
3-year DFS Stratified by TOP2A Among TC Arm 3 years from randomization into study To evaluate DFS among TC in TOP2A altered (amplified, deleted, or overexpressed at the protein level) early stage HER2-negative breast cancer.
3-year DFS Stratified by TOP2A Among TAC Arm 3 years from randomization into study To evaluate DFS among TAC in TOP2A altered (amplified, deleted, or overexpressed at the protein level) early stage HER2-negative breast cancer.
Trial Locations
- Locations (91)
Texas Cancer Center at Medical City
🇺🇸Dallas, Texas, United States
Chattanooga Oncology & Hematology Associates, PC
🇺🇸Chattanooga, Tennessee, United States
Hematology Oncology Associates of IL
🇺🇸Chicago, Illinois, United States
Central Indiana Cancer Centers
🇺🇸Indianapolis, Indiana, United States
Minnesota Oncology Hematology, P.A.
🇺🇸Minneapolis, Minnesota, United States
HOAST-Medical Dr.
🇺🇸San Antonio, Texas, United States
Oncology Hematology Care, Inc.
🇺🇸Cincinnati, Ohio, United States
Texas Oncology, P.A.
🇺🇸Houston, Texas, United States
South Texas Oncology and Hematology, P.A.
🇺🇸San Antonio, Texas, United States
San Antonio Tumor and Blood Clinic
🇺🇸San Antonio, Texas, United States
Hematology Oncology Associates
🇺🇸Phoenix, Arizona, United States
The Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Hope Center
🇺🇸Terre Haute, Indiana, United States
Kansas City Cancer Centers-Southwest
🇺🇸Overland Park, Kansas, United States
Maryland Oncology Hematology, P.A.
🇺🇸Columbia, Maryland, United States
New York Oncology Hematology, P.C.
🇺🇸Albany, New York, United States
Cancer Centers of North Carolina
🇺🇸Raleigh, North Carolina, United States
Interlakes Oncology Hematology, PC
🇺🇸Rochester, New York, United States
Greater Dayton Cancer Center
🇺🇸Kettering, Ohio, United States
Medical Oncology Associates
🇺🇸Kingston, Pennsylvania, United States
Cancer Centers of the Carolinas
🇺🇸Greenville, South Carolina, United States
Texas Oncology Cancer Center
🇺🇸Austin, Texas, United States
Texas Cancer Center
🇺🇸Denton, Texas, United States
Texas Oncology, P.A.-Amarillo
🇺🇸Amarillo, Texas, United States
Mamie McFaddin Ward Cancer Center
🇺🇸Beaumont, Texas, United States
Texas Oncology
🇺🇸Garland, Texas, United States
Lake Vista Cancer Center
🇺🇸Lewisville, Texas, United States
Longview Cancer Center
🇺🇸Longview, Texas, United States
Texas Oncology-Odessa
🇺🇸Odessa, Texas, United States
Paris Regional Cancer Center
🇺🇸Paris, Texas, United States
Texas Oncology PA
🇺🇸Webster, Texas, United States
Texoma Cancer Center
🇺🇸Wichita Falls, Texas, United States
Pudget Sound Cancer Center-Edmonds
🇺🇸Edmonds, Washington, United States
Puget Sound Cancer Center-Seattle
🇺🇸Seattle, Washington, United States
Cancer Care Northwest-South
🇺🇸Spokane, Washington, United States
Yakima Valley Mem Hosp/North Star Lodge
🇺🇸Yakima, Washington, United States
Central Hematology Oncology Medical Group, Inc.
🇺🇸Alhambra, California, United States
Arizona Oncology Associates DBA HOPE
🇺🇸Tucson, Arizona, United States
Northern AZ Hematology Oncology Associates-AOA
🇺🇸Sedona, Arizona, United States
Flordia Cancer Specialist
🇺🇸Fort Myers, Florida, United States
Northwest Georgia Oncology Centers, PC
🇺🇸Marietta, Georgia, United States
University of California-Los Angeles
🇺🇸Los Angeles, California, United States
North Valley Hematology/Oncology Medical Group
🇺🇸Northridge, California, United States
Wilshire Oncology Medical Group
🇺🇸La Verne, California, United States
Cancer Centers of Florida, P.A.
🇺🇸Ocoee, Florida, United States
Pacific Shores Medical Group
🇺🇸Long Beach, California, United States
Antelope Valley Cancer Center
🇺🇸Lancaster, California, United States
SAMSUM Clinic
🇺🇸Santa Barbara, California, United States
Melbourne Internal Medicine Associates
🇺🇸Melbourne, Florida, United States
Central Coast Medical Oncology Corporation
🇺🇸Santa Maria, California, United States
Advanced Medical Specialist
🇺🇸Miami, Florida, United States
Ventura County Hematology-Oncology Specialist
🇺🇸Oxnard, California, United States
Santa Barabra Hematology Oncology Medical Group, Inc.
🇺🇸Santa Barbara, California, United States
Suburban Hematology-Oncology Associates, PC
🇺🇸Lawrenceville, Georgia, United States
Ocala Oncology Center
🇺🇸Ocala, Florida, United States
Comprehensive Blood and Cancer Center
🇺🇸Bakersfield, California, United States
St. Jude Hertiage Medical Group
🇺🇸Fullerton, California, United States
Florida Cancer Institute
🇺🇸New Port Richey, Florida, United States
Cancer Care & Hematology Specialists of Chicagoland
🇺🇸Niles, Illinois, United States
Alliance Hematology Oncology PA
🇺🇸Westminster, Maryland, United States
Arch Medical Services, Inc.
🇺🇸Saint Louis, Missouri, United States
Comprehensive Cancer Center of Nevada
🇺🇸Henderson, Nevada, United States
Missouri Cancer Associates
🇺🇸Columbia, Missouri, United States
Southern New Mexico Cancer Center
🇺🇸Las Cruces, New Mexico, United States
New Mexico Cancer Care Associates
🇺🇸Santa Fe, New Mexico, United States
Hematology-Oncology Associates of NNJ, P.A.
🇺🇸Morristown, New Jersey, United States
Mahoning Valley Hematology Oncology Associates
🇺🇸Boardman, Ohio, United States
Willamette Valley Cancer Center
🇺🇸Eugene, Oregon, United States
Rittenhouse Hematology/Oncology
🇺🇸Philadelphia, Pennsylvania, United States
Texas Cancer Center-Abilene (South)
🇺🇸Abilene, Texas, United States
Texas Oncology -Bedford
🇺🇸Bedford, Texas, United States
Methodist Charlton Cancer Ctr.
🇺🇸Dallas, Texas, United States
South Texas Cancer Center-McAllen
🇺🇸McAllen, Texas, United States
Texas Cancer Center of Mesquite
🇺🇸Mesquite, Texas, United States
Allison Cancer Center
🇺🇸Midland, Texas, United States
Texas Cancer Center-Sherman
🇺🇸Sherman, Texas, United States
Texas Oncology Cancer Center-Sugar Land
🇺🇸Sugar Land, Texas, United States
Tyler Cancer Center
🇺🇸Tyler, Texas, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Fairfax Northern VA Hem-Onc PC
🇺🇸Fairfax, Virginia, United States
Texas Oncology Cancer Care and Research
🇺🇸Waco, Texas, United States
Virginia Cancer Institute
🇺🇸Richmond, Virginia, United States
Onc and Hem Associates os SW VA, Inc.
🇺🇸Salem, Virginia, United States
Highline Medical Oncology
🇺🇸Burien, Washington, United States
Columbia Basin Hematology and Oncology
🇺🇸Kennewick, Washington, United States
Northwest Cancer Specialists-Vancouver
🇺🇸Vancouver, Washington, United States
Yakima Valley Memorial Hospital/North Star Lodge
🇺🇸Yakima, Washington, United States
Raleigh Regional Cancer Center
🇺🇸Beckley, West Virginia, United States
Birmingham Hematology and Oncology
🇺🇸Birmingham, Alabama, United States
Rocky Mountain Cancer Center-Rose
🇺🇸Denver, Colorado, United States
El Paso Cancer Treatment Ctr
🇺🇸El Paso, Texas, United States