Clinical trial NCT00493870: TAC Versus TC for Adjuvant Breast Cancer
Official title: Phase III Trial of TC Versus TAC in HER2-Negative Early Stage Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: US Oncology Research
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2007-06-28
Enrollment: 1961
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 3-year Invasive Disease-free Survival (IDFS) Among Analyzed ITT Patients
timeFrame: 3 years from randomization into study
measure: 3-year Invasive Disease-free Survival (IDFS) Among Per-protocol Patients
timeFrame: 3 years from randomization into study
Secondary outcomes:
measure: 3-year DFS-DCIS, OS and RFI Among Analyzed ITT Patients
timeFrame: 3 years from randomization into study
measure: 3-year DFS-DCIS, OS and RFI Among Per-protocol Patients.
timeFrame: 3 years from randomization into study
measure: Number and Frequency of Participants by TOP2A Status by Study Treatment
timeFrame: 10 years (from baseline to end of study participation)
measure: 3-year DFS Stratified by TOP2A Among TC Arm
timeFrame: 3 years from randomization into study
measure: 3-year DFS Stratified by TOP2A Among TAC Arm
timeFrame: 3 years from randomization into study
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham Hematology and Oncology
state: Alabama
city: Phoenix
country: United States
facility: Hematology Oncology Associates
state: Arizona
city: Sedona
country: United States
facility: Northern AZ Hematology Oncology Associates-AOA
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates DBA HOPE
state: Arizona
city: Alhambra
country: United States
facility: Central Hematology Oncology Medical Group, Inc.
state: California
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Fullerton
country: United States
facility: St. Jude Hertiage Medical Group
state: California
city: La Verne
country: United States
facility: Wilshire Oncology Medical Group
state: California
city: Lancaster
country: United States
facility: Antelope Valley Cancer Center
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Los Angeles
country: United States
facility: University of California-Los Angeles
state: California
city: Northridge
country: United States
facility: North Valley Hematology/Oncology Medical Group
state: California
city: Oxnard
country: United States
facility: Ventura County Hematology-Oncology Specialist
state: California
city: Santa Barbara
country: United States
facility: SAMSUM Clinic
state: California
city: Santa Barbara
country: United States
facility: Santa Barabra Hematology Oncology Medical Group, Inc.
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center-Rose
state: Colorado
city: Fort Myers
country: United States
facility: Flordia Cancer Specialist
state: Florida
city: Melbourne
country: United States
facility: Melbourne Internal Medicine Associates
state: Florida
city: Miami
country: United States
facility: Advanced Medical Specialist
state: Florida
city: New Port Richey
country: United States
facility: Florida Cancer Institute
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Ocoee
country: United States
facility: Cancer Centers of Florida, P.A.
state: Florida
city: Lawrenceville
country: United States
facility: Suburban Hematology-Oncology Associates, PC
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers, PC
state: Georgia
city: Chicago
country: United States
facility: Hematology Oncology Associates of IL
state: Illinois
city: Niles
country: United States
facility: Cancer Care & Hematology Specialists of Chicagoland
state: Illinois
city: Indianapolis
country: United States
facility: Central Indiana Cancer Centers
state: Indiana
city: Terre Haute
country: United States
facility: Hope Center
state: Indiana
city: Overland Park
country: United States
facility: Kansas City Cancer Centers-Southwest
state: Kansas
city: Columbia
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Westminster
country: United States
facility: Alliance Hematology Oncology PA
state: Maryland
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Columbia
country: United States
facility: Missouri Cancer Associates
state: Missouri
city: Saint Louis
country: United States
facility: Arch Medical Services, Inc.
state: Missouri
city: Henderson
country: United States
facility: Comprehensive Cancer Center of Nevada
state: Nevada
city: Morristown
country: United States
facility: Hematology-Oncology Associates of NNJ, P.A.
state: New Jersey
city: Las Cruces
country: United States
facility: Southern New Mexico Cancer Center
state: New Mexico
city: Santa Fe
country: United States
facility: New Mexico Cancer Care Associates
state: New Mexico
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: Rochester
country: United States
facility: Interlakes Oncology Hematology, PC
state: New York
city: Raleigh
country: United States
facility: Cancer Centers of North Carolina
state: North Carolina
city: Boardman
country: United States
facility: Mahoning Valley Hematology Oncology Associates
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Kettering
country: United States
facility: Greater Dayton Cancer Center
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Center
state: Oregon
city: Kingston
country: United States
facility: Medical Oncology Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: Rittenhouse Hematology/Oncology
state: Pennsylvania
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Oncology & Hematology Associates, PC
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute
state: Tennessee
city: Abilene
country: United States
facility: Texas Cancer Center-Abilene (South)
state: Texas
city: Amarillo
country: United States
facility: Texas Oncology, P.A.-Amarillo
state: Texas
city: Arlington
country: United States
facility: Texas Cancer Center
state: Texas
city: Austin
country: United States
facility: Texas Oncology Cancer Center
state: Texas
city: Beaumont
country: United States
facility: Mamie McFaddin Ward Cancer Center
state: Texas
city: Bedford
country: United States
facility: Texas Oncology -Bedford
state: Texas
city: Dallas
country: United States
facility: Texas Cancer Center at Medical City
state: Texas
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Dallas
country: United States
facility: Methodist Charlton Cancer Ctr.
state: Texas
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Denton
country: United States
facility: Texas Cancer Center
state: Texas
city: El Paso
country: United States
facility: El Paso Cancer Treatment Ctr
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology
state: Texas
city: Garland
country: United States
facility: Texas Oncology
state: Texas
city: Houston
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Lewisville
country: United States
facility: Lake Vista Cancer Center
state: Texas
city: Longview
country: United States
facility: Longview Cancer Center
state: Texas
city: McAllen
country: United States
facility: South Texas Cancer Center-McAllen
state: Texas
city: Mesquite
country: United States
facility: Texas Cancer Center of Mesquite
state: Texas
city: Midland
country: United States
facility: Allison Cancer Center
state: Texas
city: Odessa
country: United States
facility: Texas Oncology-Odessa
state: Texas
city: Paris
country: United States
facility: Paris Regional Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Oncology and Hematology, P.A.
state: Texas
city: San Antonio
country: United States
facility: San Antonio Tumor and Blood Clinic
state: Texas
city: San Antonio
country: United States
facility: HOAST-Medical Dr.
state: Texas
city: Sherman
country: United States
facility: Texas Cancer Center-Sherman
state: Texas
city: Sugar Land
country: United States
facility: Texas Oncology Cancer Center-Sugar Land
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center
state: Texas
city: Waco
country: United States
facility: Texas Oncology Cancer Care and Research
state: Texas
city: Webster
country: United States
facility: Texas Oncology PA
state: Texas
city: Wichita Falls
country: United States
facility: Texoma Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Fairfax Northern VA Hem-Onc PC
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Salem
country: United States
facility: Onc and Hem Associates os SW VA, Inc.
state: Virginia
city: Burien
country: United States
facility: Highline Medical Oncology
state: Washington
city: Edmonds
country: United States
facility: Pudget Sound Cancer Center-Edmonds
state: Washington
city: Kennewick
country: United States
facility: Columbia Basin Hematology and Oncology
state: Washington
city: Seattle
country: United States
facility: Puget Sound Cancer Center-Seattle
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest-South
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists-Vancouver
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Mem Hosp/North Star Lodge
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital/North Star Lodge
state: Washington
city: Beckley
country: United States
facility: Raleigh Regional Cancer Center
state: West Virginia
Study officials:
affiliation: US Oncology Research
name: Joanne L Blum, MD
role: PRINCIPAL_INVESTIGATOR
References: