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TAC Versus TC for Adjuvant Breast Cancer

Sponsor
US Oncology Research (Industry)
Overall Status
Unknown status
CT.gov ID
NCT00493870
Collaborator
Sanofi (Industry)
1,296
Enrollment
95
Locations
2
Arms
143.1
Anticipated Duration (Months)
13.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
1296 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase III Trial of TC Versus TAC in HER2-Negative Early Stage Breast Cancer Patients
Actual Study Start Date :
May 29, 2007
Actual Primary Completion Date :
May 31, 2015
Anticipated Study Completion Date :
May 1, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: TC

docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2

Drug: Docetaxel
Docetaxel 75 mg/m2 IV over 1 hour on Day 1 followed by cyclophosphamide
Other Names:
  • Taxotere

    • Drug: Cyclophosphamide
    600 mg/m2 IV over 15-30 minutes on Day 1.
    Other Names:
  • Cytoxan

    		•
    Active Comparator: TAC

    doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 and docetaxel 75 mg/m2

    Drug: Docetaxel
    Docetaxel 75 mg/m2 IV over 1 hour on Day 1 followed by cyclophosphamide
    Other Names:
  • Taxotere

    • Drug: Doxorubicin
    • Doxorubicin 50 mg/m2 IV push over 5-15 minutes via sidearm through a running IV line on Day 1, followed by cyclophosphamide 500 mg/m2 IV over 15-30 minutes on Day 1, followed by docetaxel 75 mg/m2 IV over 1 hour on Day 1. Administer pegfilgrastim 6 mg SC on Day 2 (or filgrastim 5 mcg/kg SC per standard of care).
    Other Names:
  • Adriamycin

    • Drug: Cyclophosphamide
    600 mg/m2 IV over 15-30 minutes on Day 1.
    Other Names:
  • Cytoxan

    		•

    Outcome Measures

    Primary Outcome Measures

    1. to compare the 3-year DFS of adjuvant TC versus TAC as treatment for early stage HER2-negative breast cancer. [3-year]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    A woman will be eligible for inclusion in this study if she meets all of the following criteria:

    • Age >18 to <70 years old.

    • Has known ER and PR status

    • Has HER2 nonamplified disease, confirmed by FISH

    • Has known menopausal status (see Section 7.3 for criteria)

    • 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.

    • 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

    • 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)

    • Has had no prior chemotherapy unless >5 years ago

    • Has an ECOG Performance Status (PS) 0-1

    • Has laboratory values of: See protocol for specific details

    • 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

    • 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.

    • 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

    • Has had baseline bilateral mammography

    • 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

    • 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])

    • 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

    • Has adequate tumor specimen available for FISH analysis of TOP2A status (See Appendix VI).

    • Has signed a Patient Informed Consent Form

    • Has signed a Patient Authorization Form

    Exclusion Criteria:
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Birmingham Hematology and Oncology Birmingham Alabama United States 35205
    2 Hematology Oncology Associates Phoenix Arizona United States 85012
    3 Northern AZ Hematology Oncology Associates-AOA Sedona Arizona United States 86336
    4 Arizona Oncology Associates DBA HOPE Tucson Arizona United States 85704
    5 Central Hematology Oncology Medical Group, Inc. Alhambra California United States 91801
    6 Comprehensive Blood and Cancer Center Bakersfield California United States 93309
    7 St. Jude Hertiage Medical Group Fullerton California United States 92835
    8 Wilshire Oncology Medical Group La Verne California United States 91750
    9 Antelope Valley Cancer Center Lancaster California United States 93534
    10 Pacific Shores Medical Group Long Beach California United States 90813
    11 University of California-Los Angeles Los Angeles California United States 90095
    12 North Valley Hematology/Oncology Medical Group Northridge California United States 91325
    13 Ventura County Hematology-Oncology Specialist Oxnard California United States 93030
    14 SAMSUM Clinic Santa Barbara California United States 93105
    15 Santa Barabra Hematology Oncology Medical Group, Inc. Santa Barbara California United States 93105
    16 Central Coast Medical Oncology Corporation Santa Maria California United States 93454
    17 Rocky Mountain Cancer Center-Rose Denver Colorado United States 80220
    18 Flordia Cancer Specialist Fort Myers Florida United States 33916
    19 Melbourne Internal Medicine Associates Melbourne Florida United States 32901
    20 Advanced Medical Specialist Miami Florida United States 33176
    21 Florida Cancer Institute New Port Richey Florida United States 34655
    22 Ocala Oncology Center Ocala Florida United States 34474
    23 Cancer Centers of Florida, P.A. Ocoee Florida United States 34761
    24 Suburban Hematology-Oncology Associates, PC Lawrenceville Georgia United States 30045
    25 Northwest Georgia Oncology Centers, PC Marietta Georgia United States 30060
    26 Hematology Oncology Associates of IL Chicago Illinois United States 60611
    27 Cancer Care & Hematology Specialists of Chicagoland Niles Illinois United States 60714
    28 Central Indiana Cancer Centers Indianapolis Indiana United States 46627
    29 Hope Center Terre Haute Indiana United States 47802
    30 Kansas City Cancer Centers-Southwest Overland Park Kansas United States 66210
    31 Maryland Oncology Hematology, P.A. Columbia Maryland United States 21044
    32 Alliance Hematology Oncology PA Westminster Maryland United States 21157
    33 Minnesota Oncology Hematology, P.A. Minneapolis Minnesota United States 554404
    34 Missouri Cancer Associates Columbia Missouri United States 65201
    35 Arch Medical Services, Inc. Saint Louis Missouri United States 63141
    36 Comprehensive Cancer Center of Nevada Henderson Nevada United States 89052
    37 Hematology-Oncology Associates of NNJ, P.A. Morristown New Jersey United States 07960
    38 Southern New Mexico Cancer Center Las Cruces New Mexico United States 88011
    39 New Mexico Cancer Care Associates Santa Fe New Mexico United States 87505
    40 New York Oncology Hematology, P.C. Albany New York United States 12206
    41 Interlakes Oncology Hematology, PC Rochester New York United States 14623
    42 Cancer Centers of North Carolina Raleigh North Carolina United States 27607
    43 Mahoning Valley Hematology Oncology Associates Boardman Ohio United States 44514
    44 Oncology Hematology Care, Inc. Cincinnati Ohio United States 45242
    45 Greater Dayton Cancer Center Kettering Ohio United States 45409
    46 Willamette Valley Cancer Center Eugene Oregon United States 97401
    47 Medical Oncology Associates Kingston Pennsylvania United States 18704
    48 Rittenhouse Hematology/Oncology Philadelphia Pennsylvania United States 19107
    49 Cancer Centers of the Carolinas Greenville South Carolina United States 29615
    50 Chattanooga Oncology & Hematology Associates, PC Chattanooga Tennessee United States 37404
    51 The Sarah Cannon Research Institute Nashville Tennessee United States 37203
    52 Texas Cancer Center-Abilene (South) Abilene Texas United States 79606
    53 Texas Oncology, P.A.-Amarillo Amarillo Texas United States 79106
    54 Texas Cancer Center Arlington Texas United States 76014
    55 Texas Oncology Cancer Center Austin Texas United States 78731
    56 Mamie McFaddin Ward Cancer Center Beaumont Texas United States 77702
    57 Texas Oncology -Bedford Bedford Texas United States 76022
    58 Texas Cancer Center at Medical City Dallas Texas United States 75230
    59 Texas Oncology Dallas Texas United States 75231
    60 Methodist Charlton Cancer Ctr. Dallas Texas United States 75237
    61 Texas Oncology Dallas Texas United States 75246
    62 Texas Cancer Center Denton Texas United States 76210
    63 El Paso Cancer Treatment Ctr El Paso Texas United States 79915
    64 Texas Oncology Fort Worth Texas United States 76104
    65 Texas Oncology Garland Texas United States 75042
    66 Texas Oncology, P.A. Houston Texas United States 77024
    67 Lake Vista Cancer Center Lewisville Texas United States 75067
    68 Longview Cancer Center Longview Texas United States 75601
    69 South Texas Cancer Center-McAllen McAllen Texas United States 78503
    70 Texas Cancer Center of Mesquite Mesquite Texas United States 75150
    71 Allison Cancer Center Midland Texas United States 79701
    72 Texas Oncology-Odessa Odessa Texas United States 79761
    73 Paris Regional Cancer Center Paris Texas United States 75460
    74 South Texas Oncology and Hematology, P.A. San Antonio Texas United States 78207
    75 San Antonio Tumor and Blood Clinic San Antonio Texas United States 78217
    76 HOAST-Medical Dr. San Antonio Texas United States 78229
    77 Texas Cancer Center-Sherman Sherman Texas United States 75090
    78 Texas Oncology Cancer Center-Sugar Land Sugar Land Texas United States 77479
    79 Tyler Cancer Center Tyler Texas United States 75702
    80 Texas Oncology Cancer Care and Research Waco Texas United States 76712
    81 Texas Oncology PA Webster Texas United States 77598
    82 Texoma Cancer Center Wichita Falls Texas United States 76310
    83 Fairfax Northern VA Hem-Onc PC Fairfax Virginia United States 22031
    84 Virginia Oncology Associates Norfolk Virginia United States 23502
    85 Virginia Cancer Institute Richmond Virginia United States 23230
    86 Onc and Hem Associates os SW VA, Inc. Salem Virginia United States 24153
    87 Highline Medical Oncology Burien Washington United States 98166
    88 Pudget Sound Cancer Center-Edmonds Edmonds Washington United States 98026
    89 Columbia Basin Hematology and Oncology Kennewick Washington United States 99336
    90 Puget Sound Cancer Center-Seattle Seattle Washington United States 98133
    91 Cancer Care Northwest-South Spokane Washington United States 99202
    92 Northwest Cancer Specialists-Vancouver Vancouver Washington United States 98684
    93 Yakima Valley Mem Hosp/North Star Lodge Yakima Washington United States 98902
    94 Yakima Valley Memorial Hospital/North Star Lodge Yakima Washington United States 98902
    95 Raleigh Regional Cancer Center Beckley West Virginia United States 25801

    Sponsors and Collaborators

    • US Oncology Research
    • Sanofi

    Investigators

    • Principal Investigator: Joanne L Blum, MD, US Oncology Research

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    US Oncology Research
    ClinicalTrials.gov Identifier:
    NCT00493870
    Other Study ID Numbers:
    • 06090
    • 11271
    First Posted:
    Jun 28, 2007
    Last Update Posted:
    Oct 1, 2018
    Last Verified:
    Sep 1, 2018
    Additional relevant MeSH terms:
    Breast Neoplasms
    Cyclophosphamide
    Docetaxel
    Doxorubicin

    Study Results

    No Results Posted as of Oct 1, 2018