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Tailored Neoadjuvant Chemotherapy for Stage II/III Breast Cancer With Tumor Size More Than 2 cm (TaiNAC)

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ClinicalTrials.gov Identifier: NCT00776724
Recruitment Status : Completed
First Posted : October 21, 2008
Last Update Posted : May 6, 2019
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital

Tracking Information
First Submitted Date  ICMJE October 19, 2008
First Posted Date  ICMJE October 21, 2008
Last Update Posted Date May 6, 2019
Actual Study Start Date  ICMJE May 29, 2008
Actual Primary Completion Date November 30, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 20, 2008)
To evaluate and compare the pathological complete response (pCR) rates [ Time Frame: operation after 4 cycles of neoadjuvant chemotherapy with tailored chemotherapeutic regimens or TE ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 20, 2008)
To evaluate the overall clinical response rate [ Time Frame: after 4 cycles of neoadjuvant chemotherapy with tailored chemotherapeutic regimens or TE ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tailored Neoadjuvant Chemotherapy for Stage II/III Breast Cancer With Tumor Size More Than 2 cm
Official Title  ICMJE A Randomized Phase III Study of Docetaxel/ Epirubicin Versus Tailored Regimens as Neoadjuvant Chemotherapy for Stage II/III Breast Cancer With Tumor Size More Than 2 cm
Brief Summary This is a multi-center randomized phase III trial. The purpose is to evaluate and compare the pathological complete response (pCR) rates after neoadjuvant chemotherapy with tailored chemotherapeutic regimens or standard chemotherapy for stage II/III breast cancer with tumor size more than 2 cm.
Detailed Description

This is a multicenter randomized phase III trial. The purpose is to evaluate and compare the pathological complete response (pCR) rates after neoadjuvant chemotherapy with tailored chemotherapeutic regimens or standard chemotherapy for stage II/III breast cancer with tumor size more than 2 cm.

For primary operable breast cancer, neoadjuvant chemotherapy is one of standard options. Pathological complete response (pCR) was associated with significantly improved long-term disease free and overall survival. Anthracycline/taxane-based chemotherapy regimens have been studied extensively in prospective trials and are the most frequently prescribed treatments in patients with breast cancer as neoadjuvant chemotherapy. Regimens that have been tested in large multicenter phase III trials and yielded pCR rates of at around 15% and up to 20% after 6 cycles of chemotherapy. Recent evidences have showed that the expression of several proteins in the tumor samples such as tau, topoisomerase II alpha (topo II), and ERCC1 can predict the tumor response to taxanes, anthracyclines, and platinums, respectively. We hypothesized that select chemotherapeutic agent according the expressions of drug sensitivity predictive biomarkers from patient's tumor sample may improve the efficacy of breast cancer treatment.

In this randomized phase III trial, TE (Docetaxel/ epirubicin) will be given in control arm since it is a highly active regimen for breast cancer. In the Tailored chemotherapy arm, 7 different combination chemotherapy regimens that containing 2 drugs among taxotere, epirubicin, cisplatin, vinorelbine, and 5FU, will be given according to the expressions of tumor biomarkers. The doses and schedules of those regimens are selected according published 1st line protocols for breast cancer. The primary endpoint is the pCR rate. After 4 cycles of neoadjuvant chemotherapy, under the assumption of pCR rate of 15% in TE arm, to achieve 80% power at the 5% level (one side) of significance for the detection of a 15% increase of pCR rate in tailored regimen arm, 134 patients in either arm should be included in the study. If a 10% drop-out rate and multi-center study variation effect are considered, totally 316 patients will be required.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Cancer
  • Chemotherapy
Intervention  ICMJE
  • Drug: Taxotere , Epirubicin
    Taxotere 70 mg/m2 1hr iv infusion / Epirubicin 90 mg/m2 (TE) iv infusion on day 1.
  • Drug: E-HDFL,EP,TE,N-HDFL,NP,T-HDFL,TP

    Tau+ topo II+ ERCC1+ : Epi 45mg/m2 iv / 5FU 2000mg/m2 + Lv 300mg/m2 24 hrs infusion, day 1 and 8.

    Tau+ topo II+ ERCC1- : Epi 45mg/m2 iv/ Cis 35mg/m2 24 hrs iv infusion day 1 and 8.

    Tau+ topo II- ERCC1+ : Vin 25mg/m2 iv / 5FU 2000mg/m2 + Lv 300mg/m2 24 hrs infusion, day 1 and 8.

    Tau+ topo II- ERCC1- : Cis 35mg/m2 24 hrs infusion / Vin 25mg/m2 iv day 1 and 8.

    Tau- topo II+ ERCC1+ : Docetaxel 70 mg/m2 / Epirubicin 90 mg/m2 on day 1.

    Tau- topo II+ ERCC1- : Docetaxel 70 mg/m2 / Epirubicin 90 mg/m2 on day 1.

    Tau- topo II- ERCC1+ : Tax 35mg/m2 1hr infusion / 5FU 2000mg/m2 + Lv 300mg/m2 24 hrs infusion, day 1 and 8.

    Tau- topo II- ERCC1- : Tax 35mg/m2 1hr infusion / Cis 35mg/m2 24 hrs infusion day 1 and 8.

Study Arms  ICMJE
  • Active Comparator: 1
    docetaxel-epirubicin for 4 cycles before surgery
    Intervention: Drug: Taxotere , Epirubicin
  • Experimental: 2
    Tailored regimens, base on immunohistochemical study of the tumor biopsy tissue, for 4 cycles before surgery.
    Intervention: Drug: E-HDFL,EP,TE,N-HDFL,NP,T-HDFL,TP
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 2, 2019)
166
Original Estimated Enrollment  ICMJE
 (submitted: October 20, 2008)
272
Actual Study Completion Date  ICMJE April 19, 2017
Actual Primary Completion Date November 30, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed invasive, but non-inflammatory, breast carcinoma, with stage II or III disease (AJCC 7th ed)
  • And, tumor size more than 2 cm in greatest diameter measured by estimated by CT scan or MRI
  • Documented Her2/neu negative , including score 0, 1+, or 2+ by immunohistochemistry
  • No prior radiotherapy, hormonal therapy or chemotherapy for invasive breast cancer
  • Performance status of ECOG 0, 1,
  • Female with age older than 20 years
  • Laboratory parameter

    • Absolute neutrophil count (ANC) ≧1500/mm3
    • Total bilirubin ≦2.0 times the upper limit of normal (ULM)
    • AST or ALT ≦2.5 times the upper limit of normal (ULM)
    • Platelets ≧100,000/mm3
    • Serum creatinine ≦1.5 x ULM
    • Fasting triglyceride ≧ 70 mg/dL
  • Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

  • Evidence of metastatic breast cancer or inflammatory breast cancer
  • Bilateral breast cancer, metaplastic carcinoma, or mucinous carcinoma
  • Known allergy to any of the study drugs or to agents containing Cremophor.
  • Serious intercurrent infections or medical illnesses that are uncontrolled or the control of which may be jeopardized by this therapy
  • Psychiatric disorders or other conditions regarding the subject incapable of complying with the requirements of the protocol
  • Evidence of baseline sensory or motor neuropathy
  • Pregnant or breast feeding women
  • Previous or current systemic malignancy with the exception of curatively treated non-melanoma skin cancer or cervical carcinoma in situ with a disease-free interval of at least 5 years
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00776724
Other Study ID Numbers  ICMJE 200803006M
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Taiwan University Hospital
Study Sponsor  ICMJE National Taiwan University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Yen-Shen Lu, M.D., Ph.D. Department of Oncology, National Taiwan University Hospital
Principal Investigator: Chiun-Sheng Hunag, MD,PhD Department of Surgery, National Taiwan University Hospital
PRS Account National Taiwan University Hospital
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP