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

Tracking Information

• First Submitted Date: June 1, 2009
• First Posted Date: June 3, 2009
• Last Update Posted Date: November 22, 2016
• Study Start Date: July 2009
• Actual Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 2, 2009): pathological complete remission (pCR) rate [ Time Frame: after 6 cycles of neoadjuvant therapy ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 2, 2009)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• 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
• Drug: Docetaxel, cyclophosphamide
  Docetaxel 75mg/m2, cyclophosphamide 600mg/m2 every 3 weeks for six cycles

Study Arms

• Experimental: TAC Arm
  six cycles of neoadjuvant Docetaxel, Anthracycline and Cyclophosphamide
  Intervention: Drug: Docetaxel, Anthracycline (Doxorubicin or Epirubicin), Cyclophosphamide
• Experimental: TC Arm
  six cycles of neoadjuvant Docetaxel and Cyclophosphamide
  Intervention: Drug: Docetaxel, cyclophosphamide

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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 27, 2013): 102
• Original Estimated Enrollment (submitted: June 2, 2009): 600
• Actual Study Completion Date: October 2015
• Actual Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT00912444
• Other Study ID Numbers: NATT
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Kunwei Shen, Shanghai Jiao Tong University School of Medicine
• Study Sponsor: Shanghai Jiao Tong University School of Medicine
• Collaborators: Not Provided

Investigators

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

• PRS Account: Shanghai Jiao Tong University School of Medicine
• Verification Date: November 2016