Neoadjuvant Treatment of Docetaxel, Anthracycline and Cyclophosphamide (TAC) Versus Docetaxel and Cyclophosphamide (TC) in Triple-Negative or Her2 Positive Breast Cancer (NATT)

• ClinicalTrials.gov Identifier: NCT00912444
• Recruitment Status: Terminated
• First Posted: June 3, 2009
• Last Update Posted: November 22, 2016
• Sponsor: Shanghai Jiao Tong University School of Medicine
• Information provided by (Responsible Party): Kunwei Shen, Shanghai Jiao Tong University School of Medicine

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: Docetaxel, Anthracycline (Doxorubicin or Epirubicin), Cyclophosphamide; Drug: Docetaxel, cyclophosphamide	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: July 2009
• Actual Primary Completion Date: May 2012
• Actual Study Completion Date: October 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: TAC Arm; six cycles of neoadjuvant Docetaxel, Anthracycline and Cyclophosphamide	Drug: Docetaxel, Anthracycline (Doxorubicin or Epirubicin), Cyclophosphamide; Docetaxel 75mg/m2, doxorubicin 50mg/m2 or epirubicin 60mg/m2, cyclophosphamide 500mg/m2 every 3 weeks for six cycles
Experimental: TC Arm; six cycles of neoadjuvant Docetaxel and Cyclophosphamide	Drug: Docetaxel, cyclophosphamide; Docetaxel 75mg/m2, cyclophosphamide 600mg/m2 every 3 weeks for six cycles

Outcome Measures

Primary Outcome Measures :

1. pathological complete remission (pCR) rate [ Time Frame: after 6 cycles of neoadjuvant therapy ]

Secondary Outcome Measures :

1. disease free survival (DFS) and overall survival (OS) [ Time Frame: 5-year ]
2. clinical response rate [ Time Frame: after 6 cycles of neoadjuvant therapy ]
3. safety profile [ Time Frame: during neoadjuvant therapy ]
4. breast conservation therapy (BCT) rate [ Time Frame: after surgery ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

China, Guangdong

The First People's Hospital of Foshan

Foshan, Guangdong, China, 528000

Guangdong Provincial Maternal and Child Health Hospital

Guangzhou, Guangdong, China, 510010

Guangzhou General Hospital of Guangzhou Military Area

Guangzhou, Guangdong, China, 510010

China, Hunan

Xiangya Hospital Central South University

Changsha, Hunan, China, 410008

Hunan Cancer Hospital

Changsha, Hunan, China, 410009

China, Jiangsu

Jiangyin People's Hospital

Jiangyin, Jiangsu, China, 214440

Jiangsu Cancer Hospital

Nanjing, Jiangsu, China, 210009

The Second Affilliated Hospital of Suzhou University

Suzhou, Jiangsu, China, 215004

Wujiang First People's Hospital

Wujiang, Jiangsu, China, 215200

China, Jiangxi

The third hospital of Nanchang

Nanchang, Jiangxi, China, 330009

China, Shandong

Linyi People's Hospital

Linyi, Shandong, China, 276003

China, Shanghai

Shanghai Obstetrics and Gynecology Hospital

Shanghai, Shanghai, China, 200021

Ruijin Hospital

Shanghai, Shanghai, China, 200025

Zhongshan Hospital Fudan University

Shanghai, Shanghai, China, 200032

the International Peace Maternity and Child health Hospital

Shanghai, Shanghai, China, 200033

Xin Hua Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai, China, 200092

China, Shanxi

Shanxi Provincical Cancer Hospital

Taiyuan, Shanxi, China, 030013

Fisrt Affiliated Hospital of Medical College of Xi'an Jiaotong University

Xi'an, Shanxi, China, 710061

China, Sichuan

West China Hospital Sichuan University

Chengdu, Sichuan, China, 610041

China, Xinjiang

Sinkiang Uygur Autonomous Region Cancer Hospital

Urumqi, Xinjiang, China, 830000

China, Yunnan

Yunnan Provincical Tumor Hospital

Kunming, Yunnan, China, 650106

China, Zhejiang

Obstetrics and Gynecology Hospital affiliated to Zhejiang University

Hangzhou, Zhejiang, China, 310006

Zhejiang Traditional Chinese Medical Hospital

Hangzhou, Zhejiang, China, 310006

Ningbo First People's Hospital

Ningbo, Zhejiang, China, 315010

Taizhou Hospital of Zhejiang Province

Taizhou, Zhejiang, China, 318050

The First Affilliated Hospital of Wenzhou Medical College

Wenzhou, Zhejiang, China, 325000

Ruian People's Hospital

Wenzhou, Zhejiang, China, 325208

Sponsors and Collaborators

Shanghai Jiao Tong University School of Medicine

Investigators

• Principal Investigator: Kunwei Shen; Shanghai Jiao Tong University School of Medicine

More Information

Additional Information:

published result link 

Publications:

Yang L, Li LD, Chen YD, Parkin DM. [Time trends, estimates and projects for breast cancer incidence and mortality in China]. Zhonghua Zhong Liu Za Zhi. 2006 Jun;28(6):438-40. Chinese.

Jones SE, Savin MA, Holmes FA, O'Shaughnessy JA, Blum JL, Vukelja S, McIntyre KJ, Pippen JE, Bordelon JH, Kirby R, Sandbach J, Hyman WJ, Khandelwal P, Negron AG, Richards DA, Anthony SP, Mennel RG, Boehm KA, Meyer WG, Asmar L. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006 Dec 1;24(34):5381-7. Erratum in: J Clin Oncol. 2007 May 1;25(13):1819.

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.

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.

• Responsible Party: Kunwei Shen, Professor, Shanghai Jiao Tong University School of Medicine
• ClinicalTrials.gov Identifier: NCT00912444 History of Changes
• Other Study ID Numbers: NATT
• First Posted: June 3, 2009
• Last Update Posted: November 22, 2016
• Last Verified: November 2016

Keywords provided by Kunwei Shen, Shanghai Jiao Tong University School of Medicine:

Breast Neoplasms; Neoadjuvant; Chemotherapy; Docetaxel; Cyclophosphamide; Anthracycline

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Cyclophosphamide; Docetaxel; Doxorubicin; Liposomal doxorubicin; Epirubicin; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors