Ignite Creation Date:
2024-05-06 @ 3:16 PM
Last Modification Date:
2024-10-26 @ 1:46 PM
Study NCT ID:
NCT04576143
Status:
RECRUITING
Last Update Posted:
2021-08-12
First Post:
2020-09-20
Brief Title:
Efficacy and Safety of Dose-dense Chemotherapy ddEC-ddP for Neoadjuvant Chemotherapy of HER2-negative Breast Cancer
Sponsor:
Second Affiliated Hospital School of Medicine Zhejiang University
Organization:
Second Affiliated Hospital School of Medicine Zhejiang University
Study Overview
Official Title:
Efficacy and Safety of Dose-dense Epirubicin and Cyclophosphamide Plus Paclitaxel as Neoadjuvant Chemotherapy for HER2-negative Early Breast Cancera Multicenter Randomized Controlled Trial
Status:
RECRUITING
Status Verified Date:
2021-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Recent clinical studies showed that breast cancer patients especially for those with lymph node metastasis may benefit from dose-dense chemotherapy like adriamycin and cyclophosphamide AC q2w4 paclitaxel P q2w4 However the studies on dose-dense dd regimen chemotherapy is mostly based on postoperative adjuvant chemotherapy and the optimum of dose-dense chemotherapy has not been determined for Chinese population with HER2-negative breast cancer patients In our study a prospective randomized open-label multi-center clinical study was conducted to compare the efficacy and safety of dose-dense chemotherapy regimen dd epirubicincyclophosphamide EC followed by dd paclitaxel P and conventional chemotherapy epirubicincyclophosphamide EC followed by docetaxel T as preoperative neoadjuvant chemotherapy in the treatment of HER2-negative breast cancer in Chinese population
Detailed Description:
Neoadjuvant chemotherapy refers to systemic chemotherapy as the first step for treating breast cancer patients before planned local treatment like surgery for those without distant metastasis Randomized trials of chemotherapy have demonstrated similar long-term outcomes when patients were given the same treatment preoperatively compared with postoperatively It is reported that preoperative neoadjuvant chemotherapy can facilitate breast conservation render inoperable tumors operable and provide important prognostic information at an individual patient level based on response to therapy
According to the recommendation of National Comprehensive Cancer Network NCCN guideline patients with inoperable breast cancer such as inflammatory breast cancer N3 nodal disease and T4 tumors are candidates for preoperative systemic therapy As for those operable patients with HER2-positive disease and triple-negative breast cancer TNBC if T 2 or N 1 or large primary tumor relative to breast size in a patient who desires breast conservation neoadjuvant chemotherapy is also preferred Based on the results of NSABP-27 and Aberdeen clinical trials chemotherapeutic drugs including taxanes such as docetaxel paclitaxel and anthracyclines such as doxorubicin epirubicin have become the standard neoadjuvant chemotherapy regimens for early operable patients and for HER2-negative breast cancer patients anthracyclines combined with cyclophosphamide followed by docetaxel is mostly common used
Limited to myelosuppression and bone marrow repair conventional chemotherapy cycle is usually set once every 3-4 weeks Recent years the application of granulocyte colony stimulating factor G-CSF which can shorten the recovery time of leukocytes enables dose-dense chemotherapy maximum tolerable dose every 2 weeks as a cycle to become a treatment option for high-risk patients The concept of dose-dense chemotherapy is based on a mathematical model developed by Norton and Simon and relies on an understanding of Gompertzian model of tumor growth Gompertzian kinetics explain that human neoplasms do not grow in an exponential fashion instead the cell-doubling time becomes progressively longer as the tumor growth Thus cancer treatments that reduce the size of a tumor can promote faster tumor regrowth between treatments indirectly So Norton-Simon hypothesis suggests that the most effective strategy is to expose the tumor to cytotoxic agents as frequently as possible to minimize regrowth between cycles
The CALGB 9471 used a randomized 22 factorial design to prospectively compare sequential doxorubicin paclitaxel cyclophosphamide with concurrent doxorubicin and cyclophosphamide followed by paclitaxel and to compare dose-dense schedules with conventional schedules A total of 2005 node-positive previously untreated patients were enrolled At a median follow-up of 36 months dose-dense treatment significantly improved disease-free survival DFS and overall survival OS compared with conventionally scheduled treatment The GIM2 study also demonstrated that dose-dense adjuvant chemotherapy FEC-P and EC-P every 2 weeks a cycle improved DFS and OS compared with standard interval chemotherapy every 3 weeks a cycle However the studies on dose-dense chemotherapy is mostly based on postoperative adjuvant chemotherapy We aim to conduct a prospective randomized open-label multi-center clinical study to compare the efficacy and safety of dose-dense chemotherapy dd epirubicincyclophosphamide EC followed by dd paclitaxel P and conventional chemotherapy epirubicincyclophosphamide EC followed by docetaxel T as preoperative neoadjuvant chemotherapy in the treatment of HER2-negative breast cancer in Chinese population
According to the recommendation of National Comprehensive Cancer Network NCCN guideline patients with inoperable breast cancer such as inflammatory breast cancer N3 nodal disease and T4 tumors are candidates for preoperative systemic therapy As for those operable patients with HER2-positive disease and triple-negative breast cancer TNBC if T 2 or N 1 or large primary tumor relative to breast size in a patient who desires breast conservation neoadjuvant chemotherapy is also preferred Based on the results of NSABP-27 and Aberdeen clinical trials chemotherapeutic drugs including taxanes such as docetaxel paclitaxel and anthracyclines such as doxorubicin epirubicin have become the standard neoadjuvant chemotherapy regimens for early operable patients and for HER2-negative breast cancer patients anthracyclines combined with cyclophosphamide followed by docetaxel is mostly common used
Limited to myelosuppression and bone marrow repair conventional chemotherapy cycle is usually set once every 3-4 weeks Recent years the application of granulocyte colony stimulating factor G-CSF which can shorten the recovery time of leukocytes enables dose-dense chemotherapy maximum tolerable dose every 2 weeks as a cycle to become a treatment option for high-risk patients The concept of dose-dense chemotherapy is based on a mathematical model developed by Norton and Simon and relies on an understanding of Gompertzian model of tumor growth Gompertzian kinetics explain that human neoplasms do not grow in an exponential fashion instead the cell-doubling time becomes progressively longer as the tumor growth Thus cancer treatments that reduce the size of a tumor can promote faster tumor regrowth between treatments indirectly So Norton-Simon hypothesis suggests that the most effective strategy is to expose the tumor to cytotoxic agents as frequently as possible to minimize regrowth between cycles
The CALGB 9471 used a randomized 22 factorial design to prospectively compare sequential doxorubicin paclitaxel cyclophosphamide with concurrent doxorubicin and cyclophosphamide followed by paclitaxel and to compare dose-dense schedules with conventional schedules A total of 2005 node-positive previously untreated patients were enrolled At a median follow-up of 36 months dose-dense treatment significantly improved disease-free survival DFS and overall survival OS compared with conventionally scheduled treatment The GIM2 study also demonstrated that dose-dense adjuvant chemotherapy FEC-P and EC-P every 2 weeks a cycle improved DFS and OS compared with standard interval chemotherapy every 3 weeks a cycle However the studies on dose-dense chemotherapy is mostly based on postoperative adjuvant chemotherapy We aim to conduct a prospective randomized open-label multi-center clinical study to compare the efficacy and safety of dose-dense chemotherapy dd epirubicincyclophosphamide EC followed by dd paclitaxel P and conventional chemotherapy epirubicincyclophosphamide EC followed by docetaxel T as preoperative neoadjuvant chemotherapy in the treatment of HER2-negative breast cancer in Chinese population
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None