NCT02953184

Marched Pair Study Conventional Doxorubicin(DOX) Versus Pegylated Liposomal Doxorubicin(PLD) Neoadjuvant Chemotherapy

Marched Pair Study of the Standard Chemotherapy 4doxorubicin Plus Cyclophosphamide(AC) 60 + 4 Docetaxel Protocol Versus 4 PLD C35+4 Docetaxel in Neoadjuvant Chemotherapy of Breast Cancer

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 160 (estimated)
• Sponsor: Jilin University · Academic / Other
• Sex: Female
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The regimen PLD plus cyclophosphamide 4 cycles followed by paclitaxel or docetaxel 4 cycles(noted in phase II CAPRICE) will be used as experimental group. The regimen will be compared to the standard treatment of doxorubicin plus cyclophosphamide(AC) 4 cycles followed by paclitaxel or docetaxel 4 cycles\[noted in National Comprehensive Cancer Network (NCCN) guideline\].

Detailed description

Purpose :Anthracycline based chemotherapy regimen is the milestone on the treatment of breast cancer . A sequential protocol, using docetaxel or Paclitaxel after an anthracycline-based combination is primary treatment for high-risk breast cancer .Despite its efficient antitumor activity profile, the use of conventional anthracycline in clinical practice is limited due to it's the risk of cardiac toxicity. The meta analysis show that subclinical cardiotoxicity was 17.9% whereas the incidence of clinically overt cardiotoxicity was 6.3%. Overall cardiovascular events occurred in 10.6%(Lotrisone , Am J Cardiol. 2013).Many patients have healed from breast cancer while they are snatched lives because of heart issue from chemotherapy using anthracycline. There are a lot of clinical trials exploring the possibilities of chemotherapy regimen without anthracycline ,however the recent result has shown anthracycline is indispensible for the patients whose axillary nodes are involved or triple negative breast cancer (ASCO 2016 ).So our target is to find a kind of anthracycline which is of equal efficiency with conventional anthracycline while less cardiac toxicity. Pegylated Liposomal Doxorubicin(PLD) is a novel kind of anthracycline. It distributes into cardiac cells lowly and releases Doxorubicin (DOX) slower to avoid peak plasma concentration, so it is of significant less cardiotoxicity compared to free DOX. It also achieve non-inferior efficacy at 50mg/m2 to conventional anthracycline in Metastatic Breast Cancer (MBC).( M. E. R. O'Brien, ,Annals of Oncology,2004;). PLD 35mg/m2 in combination with paclitaxel showed an overall response rate of 71% ,tolerating toxicity of the skin(3% hand-foot syndrome)and rare cardiac event( H. Gogas1, Annals of Oncology, 2002;Gil-Gil , Breast Cancer Res Treat. 2015)However, There are a crucial question is to know if 35mg/m2 PLD has equivalent efficacy with less cardiac toxicity compared with 60 mg/m2 DOX in adjuvant chemotherapy for all patients. The regimen PLD plus cyclophosphamide 4 cycles followed by paclitaxel or docetaxel 4 cycles(noted in phase II CAPRICE)will be used as experimental group. The regimen will be compared to the standard treatment of doxorubicin plus cyclophosphamide (AC)4 cycles followed by paclitaxel or docetaxel 4 cycles(noted in NCCN guideline). Condition Intervention Phase Individualized Chemotherapy Drug: Pegylated Liposomal Doxorubicin(PLD) Drug: Doxorubicin(DOX) Drug: Cyclophosphamide Drug: docetaxel or Paclitaxel Phase 2 Study Type: Interventional Study Design: Allocation: assignment based on patients desire Endpoint Classification: Safety/Efficacy Study Intervention Model: Marched pair Parallel Assignment Masking: Open Label Primary Purpose: Treatment

Conditions

• Antineoplastic Combined Chemotherapy Protocols

Interventions

Type	Name	Description
DRUG	Pegylated Liposomal Doxorubicin	35mg/m2 iv drop during the first 4 cycles every three week
DRUG	Cyclophosphamide	600mg/m2 IV drop during the first 4 cycles every three week
DRUG	Taxotere	100mg/m2 IV drop during the last 4 cycles every three week
DRUG	Dexrazoxane (DZR)	DZR will be administrated for protecting Cardiac toxicity in the group of Active comparator.
DRUG	vitamin B	Vitamin B will be administrated for protecting HFS in PLD group
DRUG	Doxorubicin	60mg/m2 Doxorubicin IV drop during the first 4 cycles every three week
PROCEDURE	Breast Conserved Surgery	Patients will undergo Breast Conserved Surgery if the tumor/breast ratio is proper and she demands to conserve the breast after 8 cycles of chemotherapy
PROCEDURE	Modified Radical Mastectomy	Patients will undergo Modified Radical Mastectomy if she does not keep her breast after 8 cycles of chemotherapy
PROCEDURE	Sentinel Lymph Node Biopsy（SLNB）	Patients will undergo Sentinel Lymph Node Biopsy（SLNB） if the evaluation of lymph node are negative after 8 cycles of chemotherapy

Timeline

• Start date: 2016-11-01
• Primary completion: 2019-11-01
• Completion: 2020-11-01
• First posted: 2016-11-02
• Last updated: 2017-12-29

Locations

1 site across 1 country: China