Ignite Creation Date:
2025-12-25 @ 2:48 AM
Ignite Modification Date:
2026-02-28 @ 2:29 PM
Study NCT ID:
NCT02484833
Status:
COMPLETED
Last Update Posted:
2020-03-31
First Post:
2015-04-26
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Erbitux MEtastatic Colorectal Cancer Strategy Study
Sponsor:
Armando Orlandi
Organization:
Study Overview
Official Title:
Erbitux MEtastatic Colorectal Cancer Strategy Study (ERMES): A Phase III Randomized Two Arm Study With FOLFIRI + Cetuximab Until Disease Progression Compared to FOLFIRI + Cetuximab for 8 Cycles Followed by Cetuximab Alone Until Disease Progression in First Line Treatment of Patients With RAS and BRAF Wild Type Metastatic Colorectal Cancer
Status:
COMPLETED
Status Verified Date:
2020-03
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:
* To investigate whether cetuximab alone (given until progression or cumulative toxicity) after 8 cycles of FOLFIRI + cetuximab results in a non inferior Progression Free Survival when compared with continuous FOLFIRI + cetuximab (given until progression or cumulative toxicity).
* To assess whether an improvement in the incidence of grade 3-4 hematological and non-hematological adverse events (AEs) can be achieved in the experimental arm (cetuximab alone after 8 cycles FOLFIRI + cetuximab) as compared to the continuous chemotherapy arm (FOLFIRI plus cetuximab)
* To explore the possibility of using liquid biopsies for molecular profiling as well as monitoring treatment activity in mCRC pts receiving cetuximab based therapy
* To assess whether an improvement in the incidence of grade 3-4 hematological and non-hematological adverse events (AEs) can be achieved in the experimental arm (cetuximab alone after 8 cycles FOLFIRI + cetuximab) as compared to the continuous chemotherapy arm (FOLFIRI plus cetuximab)
* To explore the possibility of using liquid biopsies for molecular profiling as well as monitoring treatment activity in mCRC pts receiving cetuximab based therapy
Detailed Description:
Survival of patients undergoing therapy with FOLFIRI + cetuximab seems to be related to the ability of this treatment to induce a rapid reduction in tumor mass. In the retrospective analyses of the FIRE-3 trial ETS was significantly associated with PFS and OS, suggesting that ETS reflects the existence of a selected population of patients highly sensitive to cetuximab. This permits the assumption that, once this goal has been achieved, further exposure to combined antineoplastic treatment (cytotoxic drugs and targeted therapy) may not result in improvement or preservation of the result, but only in an increase of side effects that will be additional to unavoidable disease progression. In addition, the heavy exposure to cytotoxic antineoplastic treatments may lead to bone marrow toxicity, hepatic and renal function decreases that could compromise the sequential treatment plan, negatively affecting OS. With the availability of an effective treatment such as cetuximab in monotherapy4 without major side effects on blood counts and liver and kidney function, the use of this treatment alone after achievement of the deepest clinical response could be a viable strategy to achieve a good control of the disease, limiting side effects. As shown in several studies designed to understand the most effective treatment sequence in colorectal carcinoma, the most important factor that influences the overall survival is the possibility to administer more lines of effective therapy. As a consequence, a de-intensifying strategy in a subgroup of highly selected RAS and BRAF WT population might segregate a group of patients with the largest potential for fast-primary treatment. Joining the best induction treatment with the expression of patients capability to undergo additional lines of antineoplastic therapy may be the way to optimize the continuum of care.
Recently, several mechanisms of resistance to anti-EGFR therapy have been described, but until now none may used early in order to support the treatment choice.Moreover, assessment of secondary resistance requires further tissue samples and often it is not really feasible. Therefore, a prospective multiple gene mutation analysis could meet the need of characterizing primary resistance, whereas liquid biopsy might help to recognize resistance occurring early during treatment by means of a simple and repeatable assay. Based on all these considerations, the investigators designed a strategy study: a phase III randomized two arm study with FOLFIRI + cetuximab until disease progression compared to FOLFIRI + cetuximab for 8 cycles followed by cetuximab alone until disease progression in the first line treatment of patients with RAS and BRAF WT metastatic colorectal cancer combined with a prospective multiple gene mutation analysis of both tumor tissue and blood.
Recently, several mechanisms of resistance to anti-EGFR therapy have been described, but until now none may used early in order to support the treatment choice.Moreover, assessment of secondary resistance requires further tissue samples and often it is not really feasible. Therefore, a prospective multiple gene mutation analysis could meet the need of characterizing primary resistance, whereas liquid biopsy might help to recognize resistance occurring early during treatment by means of a simple and repeatable assay. Based on all these considerations, the investigators designed a strategy study: a phase III randomized two arm study with FOLFIRI + cetuximab until disease progression compared to FOLFIRI + cetuximab for 8 cycles followed by cetuximab alone until disease progression in the first line treatment of patients with RAS and BRAF WT metastatic colorectal cancer combined with a prospective multiple gene mutation analysis of both tumor tissue and blood.
Study Oversight
Has Oversight DMC:
True
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?: