TAC Versus TC for Adjuvant Breast Cancer

Breast Cancer Clinical Trial

Official title:

Phase III Trial of TC Versus TAC in HER2-Negative Early Stage Breast Cancer Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00493870
• Other study ID #: 06090
• Secondary ID: 11271
• Status: Completed
• Phase: Phase 3
• Start date: May 29, 2007
• Est. completion date: March 30, 2020

Study information

• Verified date: February 2023
• Source: US Oncology Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1961
• Est. completion date: March 30, 2020
• Est. primary completion date: May 31, 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Docetaxel
Docetaxel 75 mg/m2 IV over 1 hour on Day 1 followed by cyclophosphamide
• 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).
• Cyclophosphamide
600 mg/m2 IV over 15-30 minutes on Day 1.

Locations

Country	Name	City	State
United States	Texas Cancer Center-Abilene (South)	Abilene	Texas
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	Central Hematology Oncology Medical Group, Inc.	Alhambra	California
United States	Texas Oncology, P.A.-Amarillo	Amarillo	Texas
United States	Texas Cancer Center	Arlington	Texas
United States	Texas Oncology Cancer Center	Austin	Texas
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Mamie McFaddin Ward Cancer Center	Beaumont	Texas
United States	Raleigh Regional Cancer Center	Beckley	West Virginia
United States	Texas Oncology -Bedford	Bedford	Texas
United States	Birmingham Hematology and Oncology	Birmingham	Alabama
United States	Mahoning Valley Hematology Oncology Associates	Boardman	Ohio
United States	Highline Medical Oncology	Burien	Washington
United States	Chattanooga Oncology & Hematology Associates, PC	Chattanooga	Tennessee
United States	Hematology Oncology Associates of IL	Chicago	Illinois
United States	Oncology Hematology Care, Inc.	Cincinnati	Ohio
United States	Maryland Oncology Hematology, P.A.	Columbia	Maryland
United States	Missouri Cancer Associates	Columbia	Missouri
United States	Methodist Charlton Cancer Ctr.	Dallas	Texas
United States	Texas Cancer Center at Medical City	Dallas	Texas
United States	Texas Oncology	Dallas	Texas
United States	Texas Oncology	Dallas	Texas
United States	Texas Cancer Center	Denton	Texas
United States	Rocky Mountain Cancer Center-Rose	Denver	Colorado
United States	Pudget Sound Cancer Center-Edmonds	Edmonds	Washington
United States	El Paso Cancer Treatment Ctr	El Paso	Texas
United States	Willamette Valley Cancer Center	Eugene	Oregon
United States	Fairfax Northern VA Hem-Onc PC	Fairfax	Virginia
United States	Flordia Cancer Specialist	Fort Myers	Florida
United States	Texas Oncology	Fort Worth	Texas
United States	St. Jude Hertiage Medical Group	Fullerton	California
United States	Texas Oncology	Garland	Texas
United States	Cancer Centers of the Carolinas	Greenville	South Carolina
United States	Comprehensive Cancer Center of Nevada	Henderson	Nevada
United States	Texas Oncology, P.A.	Houston	Texas
United States	Central Indiana Cancer Centers	Indianapolis	Indiana
United States	Columbia Basin Hematology and Oncology	Kennewick	Washington
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Medical Oncology Associates	Kingston	Pennsylvania
United States	Wilshire Oncology Medical Group	La Verne	California
United States	Antelope Valley Cancer Center	Lancaster	California
United States	Southern New Mexico Cancer Center	Las Cruces	New Mexico
United States	Suburban Hematology-Oncology Associates, PC	Lawrenceville	Georgia
United States	Lake Vista Cancer Center	Lewisville	Texas
United States	Pacific Shores Medical Group	Long Beach	California
United States	Longview Cancer Center	Longview	Texas
United States	University of California-Los Angeles	Los Angeles	California
United States	Northwest Georgia Oncology Centers, PC	Marietta	Georgia
United States	South Texas Cancer Center-McAllen	McAllen	Texas
United States	Melbourne Internal Medicine Associates	Melbourne	Florida
United States	Texas Cancer Center of Mesquite	Mesquite	Texas
United States	Advanced Medical Specialist	Miami	Florida
United States	Allison Cancer Center	Midland	Texas
United States	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota
United States	Hematology-Oncology Associates of NNJ, P.A.	Morristown	New Jersey
United States	The Sarah Cannon Research Institute	Nashville	Tennessee
United States	Florida Cancer Institute	New Port Richey	Florida
United States	Cancer Care & Hematology Specialists of Chicagoland	Niles	Illinois
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	North Valley Hematology/Oncology Medical Group	Northridge	California
United States	Ocala Oncology Center	Ocala	Florida
United States	Cancer Centers of Florida, P.A.	Ocoee	Florida
United States	Texas Oncology-Odessa	Odessa	Texas
United States	Kansas City Cancer Centers-Southwest	Overland Park	Kansas
United States	Ventura County Hematology-Oncology Specialist	Oxnard	California
United States	Paris Regional Cancer Center	Paris	Texas
United States	Rittenhouse Hematology/Oncology	Philadelphia	Pennsylvania
United States	Hematology Oncology Associates	Phoenix	Arizona
United States	Cancer Centers of North Carolina	Raleigh	North Carolina
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Interlakes Oncology Hematology, PC	Rochester	New York
United States	Arch Medical Services, Inc.	Saint Louis	Missouri
United States	Onc and Hem Associates os SW VA, Inc.	Salem	Virginia
United States	HOAST-Medical Dr.	San Antonio	Texas
United States	San Antonio Tumor and Blood Clinic	San Antonio	Texas
United States	South Texas Oncology and Hematology, P.A.	San Antonio	Texas
United States	SAMSUM Clinic	Santa Barbara	California
United States	Santa Barabra Hematology Oncology Medical Group, Inc.	Santa Barbara	California
United States	New Mexico Cancer Care Associates	Santa Fe	New Mexico
United States	Central Coast Medical Oncology Corporation	Santa Maria	California
United States	Puget Sound Cancer Center-Seattle	Seattle	Washington
United States	Northern AZ Hematology Oncology Associates-AOA	Sedona	Arizona
United States	Texas Cancer Center-Sherman	Sherman	Texas
United States	Cancer Care Northwest-South	Spokane	Washington
United States	Texas Oncology Cancer Center-Sugar Land	Sugar Land	Texas
United States	Hope Center	Terre Haute	Indiana
United States	Arizona Oncology Associates DBA HOPE	Tucson	Arizona
United States	Tyler Cancer Center	Tyler	Texas
United States	Northwest Cancer Specialists-Vancouver	Vancouver	Washington
United States	Texas Oncology Cancer Care and Research	Waco	Texas
United States	Texas Oncology PA	Webster	Texas
United States	Alliance Hematology Oncology PA	Westminster	Maryland
United States	Texoma Cancer Center	Wichita Falls	Texas
United States	Yakima Valley Mem Hosp/North Star Lodge	Yakima	Washington
United States	Yakima Valley Memorial Hospital/North Star Lodge	Yakima	Washington

Sponsors (2)

Lead Sponsor	Collaborator
US Oncology Research	Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3-year Invasive Disease-free Survival (IDFS) Among Analyzed ITT Patients	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 years from randomization into study
Primary	3-year Invasive Disease-free Survival (IDFS) Among Per-protocol Patients	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.	3 years from randomization into study
Secondary	3-year DFS-DCIS, OS and RFI Among Analyzed ITT Patients	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 years from randomization into study
Secondary	3-year DFS-DCIS, OS and RFI Among Per-protocol Patients.	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.	3 years from randomization into study
Secondary	Number and Frequency of Participants by TOP2A Status by Study Treatment	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	10 years (from baseline to end of study participation)
Secondary	3-year DFS Stratified by TOP2A Among TC Arm	To evaluate DFS among TC in TOP2A altered (amplified, deleted, or overexpressed at the protein level) early stage HER2-negative breast cancer.	3 years from randomization into study
Secondary	3-year DFS Stratified by TOP2A Among TAC Arm	To evaluate DFS among TAC in TOP2A altered (amplified, deleted, or overexpressed at the protein level) early stage HER2-negative breast cancer.	3 years from randomization into study