Clinical trial NCT00912444: Neoadjuvant Treatment of Docetaxel, Anthracycline and Cyclophosphamide (TAC) Versus Docetaxel and Cyclophosphamide (TC) in Triple-Negative or Her2 Positive Breast Cancer
Official title: A Multi-Center, Randomized Study of Docetaxel, Anthracycline and Cyclophosphamide (TAC) Versus Docetaxel and Cyclophosphamide (TC) in Neoadjuvant Treatment of Triple-Negative or Her2 Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Breast Neoplasms
Neoadjuvant
Chemotherapy
Docetaxel
Cyclophosphamide
Anthracycline
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2009-06-03
Enrollment: 102
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 study is to compare the pathological complete response (pCR) rate in triple-negative or Her2 positive breast cancer patients treated with neoadjuvant docetaxel, anthracycline and cyclophosphamide (TAC) or docetaxel and cyclophosphamide (TC) regimen.

Detailed description: Breast cancer is the leading cause of cancer in women in China. Neoadjuvant chemotherapy for treatment of locally advanced breast cancer has become a standard therapy. Results from neoadjuvant trials have shown that pathological complete response (pCR) is an independent predictor of outcome. Docetaxel was introduced into clinical practice in the early 1990s and has demonstrated good activity in the adjuvant and metastatic settings. Both TC and TAC are effective regimens in the adjuvant setting. The most optimal regimen in the neoadjuvant treatment is however unknown. This is especially true in triple-negative or HER2 positive breast cancer. This study will evaluate the pCR rate of TAC and TC as neoadjuvant treatment for triple-negative or HER2 positive breast cancer.

Eligibility criteria: Inclusion Criteria:

* Women aged ≥ 18 years and \< 70 years
* Karnofsky performance status (KPS) ≥ 70
* At least one measurable disease according to the RECIST. histologically confirmed invasive breast cancer (excluding inflammatory breast cancer), T2N1 or locally advanced breast cancer (T3-4N0-3 or T0-4N2-3)
* Biopsy specimens are available for ER, PgR and Her2 detection, patients should be with triple negative or Her2 positive breast cancer, Her2 positivity is defined as FISH/CISH Her2 positive or IHC Her2 3+, Triple-negative disease defined as negativity for ER, PgR and Her2
* Adequate bone marrow function: Neutrophil ≥ 1.5\*109/L; Hb ≥ 100g/L; PLT ≥ 100\*109/L
* An estimated life expectancy of at least 12 months
* Willing to take biopsy before neoadjuvant chemotherapy and patients must be accessible for treatment and follow-up
* Women with potential child-bearing must have a negative pregnancy test (urine or serum) within 7 days of drug administration and agree to use an acceptable method of birth control to avoid pregnancy for the duration of the study
* Written informed consent according to the GCP

Exclusion Criteria:

* Prior systemic or loco-regional treatment of breast cancer, including chemotherapy
* Metastatic breast cancer
* With a history of malignant tumor except uterine cervix cancer in situ or skin basal cell carcinoma
* Patients with medical conditions that indicate intolerant to neoadjuvant therapy and related treatment, including uncontrolled pulmonary disease, diabetes mellitis, severe infection, active peptic ulcer, coagulation disorder, connective tissue disease or myelo-suppressive disease
* inadequate liver function (bilirubin \> 1.0 times upper normal limit \[UNL\] and ALT and/or AST\> 1.5 UNL associated with alkaline phosphatase \> 2.5 UNL; inadequate renal function (creatinine \> 1.0 times UNL and in case of limit value, Creatinine clearance \< 60 ml/min)
* Contraindication for using dexamethasone
* History of congestive heart failure, uncontrolled or symptomatic angina pectoris, arrhythmia or myocardial infarction; poorly controlled hypertension (systolic BP \> 180 mmHg or diastolic BP \> 100 mmHg)
* Has peripheral neuropathy ≥ grade 1
* Patient is pregnant or breast feeding
* Known severe hypersensitivity to any drugs in this study
* Treatment with any investigational drugs within 30 days before the beginning of study treatment

Primary outcomes:
measure: pathological complete remission (pCR) rate
timeFrame: after 6 cycles of neoadjuvant therapy
Secondary outcomes:
measure: disease free survival (DFS) and overall survival (OS)
timeFrame: 5-year
measure: clinical response rate
timeFrame: after 6 cycles of neoadjuvant therapy
measure: safety profile
timeFrame: during neoadjuvant therapy
measure: breast conservation therapy (BCT) rate
timeFrame: after surgery
Other outcomes:
Locations:
city: Foshan
country: China
facility: The First People's Hospital of Foshan
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial Maternal and Child Health Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou General Hospital of Guangzhou Military Area
state: Guangdong
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Jiangyin
country: China
facility: Jiangyin People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The Second Affilliated Hospital of Suzhou University
state: Jiangsu
city: Wujiang
country: China
facility: Wujiang First People's Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The third hospital of Nanchang
state: Jiangxi
city: Linyi
country: China
facility: Linyi People's Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Obstetrics and Gynecology Hospital
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
state: Shanghai
city: Shanghai
country: China
facility: the International Peace Maternity and Child health Hospital
state: Shanghai
city: Shanghai
country: China
facility: Xin Hua Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Provincical Cancer Hospital
state: Shanxi
city: Xi'an
country: China
facility: Fisrt Affiliated Hospital of Medical College of Xi'an Jiaotong University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital Sichuan University
state: Sichuan
city: Urumqi
country: China
facility: Sinkiang Uygur Autonomous Region Cancer Hospital
state: Xinjiang
city: Kunming
country: China
facility: Yunnan Provincical Tumor Hospital
state: Yunnan
city: Hangzhou
country: China
facility: Obstetrics and Gynecology Hospital affiliated to Zhejiang University
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Traditional Chinese Medical Hospital
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo First People's Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affilliated Hospital of Wenzhou Medical College
state: Zhejiang
city: Wenzhou
country: China
facility: Ruian People's Hospital
state: Zhejiang
Study officials:
affiliation: Shanghai Jiao Tong University School of Medicine
name: Kunwei Shen
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Martin M, Pienkowski T, Mackey J, Pawlicki M, Guastalla JP, Weaver C, Tomiak E, Al-Tweigeri T, Chap L, Juhos E, Guevin R, Howell A, Fornander T, Hainsworth J, Coleman R, Vinholes J, Modiano M, Pinter T, Tang SC, Colwell B, Prady C, Provencher L, Walde D, Rodriguez-Lescure A, Hugh J, Loret C, Rupin M, Blitz S, Jacobs P, Murawsky M, Riva A, Vogel C; Breast Cancer International Research Group 001 Investigators. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005 Jun 2;352(22):2302-13. doi: 10.1056/NEJMoa043681.
citation: Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, Hess KR, Stec J, Ayers M, Wagner P, Morandi P, Fan C, Rabiul I, Ross JS, Hortobagyi GN, Pusztai L. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005 Aug 15;11(16):5678-85. doi: 10.1158/1078-0432.CCR-04-2421.