Tailored Neoadjuvant Chemotherapy for Stage II/III Breast Cancer With Tumor Size More Than 2 cm (TaiNAC)
Recruitment status was: Recruiting
Drug: Taxotere , Epirubicin
|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|
- 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 ]
- 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 ]
|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)|
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.
Tailored regimens, base on immunohistochemical study of the tumor biopsy tissue, for 4 cycles before surgery.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00776724
|National Taiwan University Hospital|
|Taipei, Taiwan, 100|
|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|