Ignite Creation Date:
2024-05-06 @ 7:50 AM
Last Modification Date:
2024-10-26 @ 11:53 AM
Study NCT ID:
NCT02616848
Status:
UNKNOWN
Last Update Posted:
2015-11-30
First Post:
2015-11-21
Brief Title:
Safety and Tolerability of Everolimus in Combination With Eribulin in Triple-negative Breast Cancers
Sponsor:
Istituti Ospitalieri di Cremona
Organization:
Istituti Ospitalieri di Cremona
Study Overview
Official Title:
None
Status:
UNKNOWN
Status Verified Date:
2015-11
Last Known Status:
RECRUITING
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:
Treatment of triple negative breast cancer TNBC relies heavily on different regimes of chemotherapeutic agents but remains one of the most challenging subtypes to treat because of the lack of specific therapies Despite being sensitive to chemotherapy many women with TNBC relapse quickly developing locoregional recurrence or visceral metastasis Toxicity and chemotherapy resistance are still major limitations in the treatment of patients with TNBC Despite current trend of targeted therapy development cytotoxic agents are a mainstay of treatment of patients with breast cancer Further research into new combination of different compounds is needed in order to maximise benefit whilst minimising toxicity
The phosphoinositide 3-kinase PI3K pathway is associated with resistance to a variety of anti-tumor agents This has been described pre-clinically with cytotoxic chemotherapeutic agents with varying mechanisms of action including taxanes and DNA-damaging agents In the clinic activated PI3K in tumors has been correlated with decreased response to therapy and worse clinical outcomes
The recent biological findings suggest that a PI3Kmammalian target of rapamycin mTOR inhibitors may increase the efficacy of chemotherapeutic agents which are considered standard of care SOC for the treatment of several solid tumors
The study by the Unitaed state Oncology Research of Huston and the Sarah Cannon Cancer Center randomized 1830 patients with high risk breast cancer to the standard adjuvant treatment with adriamicin cyclophosphamide followed by paclitaxel versus the experimental adjuvant treatment with adriamicin taxotere AT followed by paclitaxel At 5-years of follow up the AT followed by paclitaxel produced significantly better overall survival p0054 and improved disease free survival DFS p019 Among TNBC patients both DFS 74 versus 79 p01 and overall survival OS 79 versus 84 p0037 were better in experimental arm However the main reasons for patients being taken off study treatment were toxicity 85 patients in the control arm and 128 in the experimental arm and consent withdrawal 18 patients in the control arm and 30 patients in the experimental arm For this reason research into alternatives has intensified thus resulting in the discovery and development of new compounds with a more tolerable profile as compared with paclitaxel
Among the total of 762 patients enrolled into Eisai Metastatic Breast Cancer Study Assessing Physicians Choice Versus E7389 EMBRACE trial 19 had TNBC Of note eribulin was most effective in hormone receptor-negative patients and in TNBC patients who had a 29 risk reduction Treatment with eribulin was well tolerated Neutropenia leucopenia peripheral neuropathy and astheniafatigue were the most common adverse events reported at Common Terminology Criteria for Adverse Events CTCAE grades 3 and 4 Neutropenia was the most common adverse events reported at CTCAE grade 4 in the eribulin group 241
Based on findings to date eribulin is an attractive agent and its role in combination with new compounds such as everolimus deserves further investigations Their combination might lead to more profound effects on tumor cell biology of triple negative metastatic breast cancer
During the course of the trial dose reductions for each combination will be permitted in patients who cannot tolerate the starting dose
The phosphoinositide 3-kinase PI3K pathway is associated with resistance to a variety of anti-tumor agents This has been described pre-clinically with cytotoxic chemotherapeutic agents with varying mechanisms of action including taxanes and DNA-damaging agents In the clinic activated PI3K in tumors has been correlated with decreased response to therapy and worse clinical outcomes
The recent biological findings suggest that a PI3Kmammalian target of rapamycin mTOR inhibitors may increase the efficacy of chemotherapeutic agents which are considered standard of care SOC for the treatment of several solid tumors
The study by the Unitaed state Oncology Research of Huston and the Sarah Cannon Cancer Center randomized 1830 patients with high risk breast cancer to the standard adjuvant treatment with adriamicin cyclophosphamide followed by paclitaxel versus the experimental adjuvant treatment with adriamicin taxotere AT followed by paclitaxel At 5-years of follow up the AT followed by paclitaxel produced significantly better overall survival p0054 and improved disease free survival DFS p019 Among TNBC patients both DFS 74 versus 79 p01 and overall survival OS 79 versus 84 p0037 were better in experimental arm However the main reasons for patients being taken off study treatment were toxicity 85 patients in the control arm and 128 in the experimental arm and consent withdrawal 18 patients in the control arm and 30 patients in the experimental arm For this reason research into alternatives has intensified thus resulting in the discovery and development of new compounds with a more tolerable profile as compared with paclitaxel
Among the total of 762 patients enrolled into Eisai Metastatic Breast Cancer Study Assessing Physicians Choice Versus E7389 EMBRACE trial 19 had TNBC Of note eribulin was most effective in hormone receptor-negative patients and in TNBC patients who had a 29 risk reduction Treatment with eribulin was well tolerated Neutropenia leucopenia peripheral neuropathy and astheniafatigue were the most common adverse events reported at Common Terminology Criteria for Adverse Events CTCAE grades 3 and 4 Neutropenia was the most common adverse events reported at CTCAE grade 4 in the eribulin group 241
Based on findings to date eribulin is an attractive agent and its role in combination with new compounds such as everolimus deserves further investigations Their combination might lead to more profound effects on tumor cell biology of triple negative metastatic breast cancer
During the course of the trial dose reductions for each combination will be permitted in patients who cannot tolerate the starting dose
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None