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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by National Taiwan University Hospital
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00776724
First received: October 19, 2008
Last updated: November 15, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Chemotherapy
Drug: Taxotere , Epirubicin
Drug: E-HDFL,EP,TE,N-HDFL,NP,T-HDFL,TP
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the overall clinical response rate [ Time Frame: after 4 cycles of neoadjuvant chemotherapy with tailored chemotherapeutic regimens or TE ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 272
Study Start Date: November 2008
Estimated Study Completion Date: May 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
docetaxel-epirubicin for 4 cycles before surgery
Drug: Taxotere , Epirubicin
Taxotere 70 mg/m2 1hr iv infusion / Epirubicin 90 mg/m2 (TE) iv infusion on day 1.
Experimental: 2
Tailored regimens, base on immunohistochemical study of the tumor biopsy tissue, for 4 cycles before surgery.
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.


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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00776724

Contacts
Contact: Yen-Shen Lu, M.D., Ph.D. 886-223123456 ext 67009 yslu@ntu.edu.tw

Locations
Taiwan
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Principal Investigator: Yen-Shen Lu, M.D., Ph.D.         
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
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
  More Information

No publications provided

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT00776724     History of Changes
Other Study ID Numbers: 200803006M
Study First Received: October 19, 2008
Last Updated: November 15, 2012
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
breast ca
phase III
Tailored neoadjuvant chemotherapy
stage II/III

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Epirubicin
Docetaxel
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014