Ignite Creation Date:
2024-05-06 @ 10:48 AM
Last Modification Date:
2024-10-26 @ 12:36 PM
Study NCT ID:
NCT03358004
Status:
TERMINATED
Last Update Posted:
2018-10-05
First Post:
2017-11-13
Brief Title:
the Role of Two Different Metronomic Chemotherapy Regimens in Locally Advanced or Metastatic Triple Negative Breast Cancer Patients TNBC as Maintenance Therapy After First Line Treatment
Sponsor:
Mario Negri Institute for Pharmacological Research
Organization:
Mario Negri Institute for Pharmacological Research
Study Overview
Official Title:
An International Multicenter Phase II Randomized Parallel-arm Trial Investigating the Role of Two Different Metronomic Chemotherapy Regimens in Locally Advanced or Metastatic Triple Negative Breast Cancer Patients TNBC as Maintenance Therapy After First Line Treatment
Status:
TERMINATED
Status Verified Date:
2018-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Low accrual rate
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
VICTOR3
Brief Summary:
TNBC defined by the lack of immunohistochemical staining for oestrogen receptors progesterone receptors and lack of overexpression or amplification of HER2neu has an aggressive biological behaviour marked by increased risk of recurrence and poorer survival compared with hormone receptor-positive subtypes
The key points for the rationale of the present study are
1 Despite different efforts for improving the outcome of TNBC patients the median distant-disease free interval for relapsed triple-negative breast cancer is about 1-2 years and the median survival for metastatic TNBC is approximately one year
2 International guidelines currently recommend polychemotherapy instead of sequential single agents as first-line treatment in this subgroup of patients but no data is available at the moment regarding the optimal duration of chemotherapy
3 There is growing evidence to suggest that platinum-based therapy may have a role in both advanced and early-stage TNBC though results are not definitive Three randomized phase II neoadjuvant trials have been reported two of which demonstrated an improvement in pathological complete response pCR rates when carboplatin is added to anthracycline and taxane-based chemotherapy though this pCR improvement came at the cost of an increase in toxicity Definitive results from phase III trials demonstrating improvement in long-term outcomes such as event-free and overall survival are not yet available and it remains unclear how to optimally incorporate platinums into neoadjuvant therapy as toxicity is enhanced when platinum is incorporated as an add-on to standard combination chemotherapy backbones A randomized phase III trial comparing cisplatin plus gemcitabine to paclitaxel plus gemcitabine has been published recently After a median follow-up of 163 months in the cisplatin plus gemcitabine group and 159 months in the paclitaxel plus gemcitabine group the hazard ratio for progression-free survival was 0692 95 CI 0523-0915 pnon-inferiority00001 superiority0009 Thus cisplatin plus gemcitabine was both non-inferior to and superior to paclitaxel plus gemcitabine Median progression-free survival was 77 months 95 CI 62-93 in the cisplatin plus gemcitabine group and 65 months 58-72 in the paclitaxel plus gemcitabine group
4 In both early and advanced disease settings response rates appear to be influenced by germ line BRCA1 and BRCA2 mutation status and BRCA1 and BRCA2 mutation status has emerged as an important potential biomarker for platinum therapy Outside of the BRCA mutant setting there is certainly good reason to believe that there are patients with sporadic TNBC who stand to benefit greatly from a platinum-based approach Tumour-based assays that detect levels of genomic scarring caused by the accumulation of DNA damage over time secondary to underlying DNA repair defects such as the Myriad HRD assay have potential to identify non carriers of BRCA1 or BRCA2 mutations with BRCA-like breast cancer who may respond to DNA repair- targeted treatment strategies such as platinum agents
One of the most promising way to improve clinical outcome in poor-risk patients is represented by maintenance therapy with a non-cross resistant regimen after an induction treatment until disease progression Nevertheless the main limit to such a strategy is the choice of chemotherapy agents considering that patients could be treated for a long period of time The results of the VICTOR-1 study was recently published the aim of this study was the determination of the maximum tolerated dose of oral metronomic schedule of vinorelbine VNR in combination with fixed doses of capecitabine CAPE as well as to confirm the safety profile of the combination in a cohort of HER2-negative metastatic breast cancer patients The results demonstrated a lower incidence of hematological grade 3-4 adverse events 11 in comparison to what published in other series using the standard schedules of the two drugs The present study is designed to select the best arm between oral metronomic schedule of vinorelbine VNR and combination of oral metronomic schedule VNR with fixed doses of capecitabine CAPE as maintenance therapy in advanced TNBC patients responders after an induction treatment
The key points for the rationale of the present study are
1 Despite different efforts for improving the outcome of TNBC patients the median distant-disease free interval for relapsed triple-negative breast cancer is about 1-2 years and the median survival for metastatic TNBC is approximately one year
2 International guidelines currently recommend polychemotherapy instead of sequential single agents as first-line treatment in this subgroup of patients but no data is available at the moment regarding the optimal duration of chemotherapy
3 There is growing evidence to suggest that platinum-based therapy may have a role in both advanced and early-stage TNBC though results are not definitive Three randomized phase II neoadjuvant trials have been reported two of which demonstrated an improvement in pathological complete response pCR rates when carboplatin is added to anthracycline and taxane-based chemotherapy though this pCR improvement came at the cost of an increase in toxicity Definitive results from phase III trials demonstrating improvement in long-term outcomes such as event-free and overall survival are not yet available and it remains unclear how to optimally incorporate platinums into neoadjuvant therapy as toxicity is enhanced when platinum is incorporated as an add-on to standard combination chemotherapy backbones A randomized phase III trial comparing cisplatin plus gemcitabine to paclitaxel plus gemcitabine has been published recently After a median follow-up of 163 months in the cisplatin plus gemcitabine group and 159 months in the paclitaxel plus gemcitabine group the hazard ratio for progression-free survival was 0692 95 CI 0523-0915 pnon-inferiority00001 superiority0009 Thus cisplatin plus gemcitabine was both non-inferior to and superior to paclitaxel plus gemcitabine Median progression-free survival was 77 months 95 CI 62-93 in the cisplatin plus gemcitabine group and 65 months 58-72 in the paclitaxel plus gemcitabine group
4 In both early and advanced disease settings response rates appear to be influenced by germ line BRCA1 and BRCA2 mutation status and BRCA1 and BRCA2 mutation status has emerged as an important potential biomarker for platinum therapy Outside of the BRCA mutant setting there is certainly good reason to believe that there are patients with sporadic TNBC who stand to benefit greatly from a platinum-based approach Tumour-based assays that detect levels of genomic scarring caused by the accumulation of DNA damage over time secondary to underlying DNA repair defects such as the Myriad HRD assay have potential to identify non carriers of BRCA1 or BRCA2 mutations with BRCA-like breast cancer who may respond to DNA repair- targeted treatment strategies such as platinum agents
One of the most promising way to improve clinical outcome in poor-risk patients is represented by maintenance therapy with a non-cross resistant regimen after an induction treatment until disease progression Nevertheless the main limit to such a strategy is the choice of chemotherapy agents considering that patients could be treated for a long period of time The results of the VICTOR-1 study was recently published the aim of this study was the determination of the maximum tolerated dose of oral metronomic schedule of vinorelbine VNR in combination with fixed doses of capecitabine CAPE as well as to confirm the safety profile of the combination in a cohort of HER2-negative metastatic breast cancer patients The results demonstrated a lower incidence of hematological grade 3-4 adverse events 11 in comparison to what published in other series using the standard schedules of the two drugs The present study is designed to select the best arm between oral metronomic schedule of vinorelbine VNR and combination of oral metronomic schedule VNR with fixed doses of capecitabine CAPE as maintenance therapy in advanced TNBC patients responders after an induction treatment
Detailed Description:
None
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