Ignite Creation Date:
2024-05-06 @ 7:18 PM
Last Modification Date:
2024-10-26 @ 3:04 PM
Study NCT ID:
NCT05962502
Status:
RECRUITING
Last Update Posted:
2023-08-31
First Post:
2023-07-17
Brief Title:
Cetuximab Plus Irinotecan in Patients With NeoRAS Wild-type Metastatic Colorectal Cancer In Third-line Therapy
Sponsor:
Sun Yat-sen University
Organization:
Sun Yat-sen University
Study Overview
Official Title:
A Single-arm Open-label Phase II Clinical Study of Cetuximab Plus Irinotecan in Patients With NeoRAS Wild-type Metastatic Colorectal Cancer In Third-line Therapy
Status:
RECRUITING
Status Verified Date:
2023-08
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:
This is a single-arm open-label phase II clinical trial The goal of this study is to evaluate the efficacy and safety of cetuximab plus irinotecan in patients with NeoRAS wild-type primary left-sided mCRC in third-line therapy
Detailed Description:
At present the third-line therapy in China includes 3 anti-angiogenic small molecule tyrosine kinase TKI inhibitors namely regorafenib fruquintinib and oral chemotherapeutic agent TAS-102There are high-level evidences for the above 3 drugs but their therapeutic effects are still unsatisfactory with the progression-free survival PFS of only 2-4 months As a result more effective regimens need to be explored The BOND study found that in mCRC patients with RAS wild-type and irinotecan resistance cetuximab combined with irinotecan as the third-line therapy could effectively reverse irinotecan resistance with an ORR of 229 The CRIKET study assessed the effect of cetuximab combined with irinotecan in later-line setting for advanced CRC the result showed that the cetuximab combined with irinotecan therapy achieved an objective response rate ORR of 21 95 CI 10-40 In the subgroup analysis compared with patients with mutations patients with RAS wild-type confirmed by circulating tumor DNA ctDNA had longer PFS benefit 40 months vs 19 months which suggested that patients with RAS wild-type mCRC might still benefit from cetuximab plus irinotecan re-challenge in third-line setting after cetuximab treatment However third-line therapy options are still limited for another 35 to 40 patients with RAS wide-type mCRC and the prognosis for these patients is relatively poor More studies are needed to explore other effective regimens
ctDNA or liquid biopsy technology can detect DNA released from tumor cells into the blood Moreover it has some detecting advantages such as real-time dynamic comprehensive and noninvasive More and more studies have shown that this technology is promising and can be widely applied in the whole disease management course of CRC patients such as early diagnosis therapeutic target detection minimal residual disease MRD detection and efficacy monitoring One of previous studies of our team found that the status of RAS and BRAF genes detected by ctDNA in advanced CRC patients would change along with treatment The study dynamically monitored ctDNA in 171 patients with unresectable mCRC The results showed that 426 of patients with initial RAS mutation were converted to RAS wild-type mCRC after the standard first-line treatment and such patients were called NeoRAS wild-type mCRC patients Other studies have also found similar phenomena but the frequency of NeoRAS wild-type conversion varies among studies 2-45 which might be related to several factors such as patients treatment stage early treatment regimen and ctDNA detection method Therefore in order to optimize treatment strategies RAS status should be retested during overall management of patients with RAS mutant mCRC
The target population for this study is patients with RASBRAF wild-type primary left-sided mCRC by blood-based ctDNA testing before third-line therapy who are initial RAS mutant and BRAF wild-type CRC patients who have disease progression after first- and second-line therapy previously treated with fluorouracil compounds oxaliplatin and irinotecan and who have tumor progression during or within 3 months after irinotecan-containing regimen This population will receive third-line therapy with cetuximab plus irinotecan bi-weekly until disease progression The primary study endpoint is ORR and the secondary study endpoints are PFS OS and drug safety
ctDNA or liquid biopsy technology can detect DNA released from tumor cells into the blood Moreover it has some detecting advantages such as real-time dynamic comprehensive and noninvasive More and more studies have shown that this technology is promising and can be widely applied in the whole disease management course of CRC patients such as early diagnosis therapeutic target detection minimal residual disease MRD detection and efficacy monitoring One of previous studies of our team found that the status of RAS and BRAF genes detected by ctDNA in advanced CRC patients would change along with treatment The study dynamically monitored ctDNA in 171 patients with unresectable mCRC The results showed that 426 of patients with initial RAS mutation were converted to RAS wild-type mCRC after the standard first-line treatment and such patients were called NeoRAS wild-type mCRC patients Other studies have also found similar phenomena but the frequency of NeoRAS wild-type conversion varies among studies 2-45 which might be related to several factors such as patients treatment stage early treatment regimen and ctDNA detection method Therefore in order to optimize treatment strategies RAS status should be retested during overall management of patients with RAS mutant mCRC
The target population for this study is patients with RASBRAF wild-type primary left-sided mCRC by blood-based ctDNA testing before third-line therapy who are initial RAS mutant and BRAF wild-type CRC patients who have disease progression after first- and second-line therapy previously treated with fluorouracil compounds oxaliplatin and irinotecan and who have tumor progression during or within 3 months after irinotecan-containing regimen This population will receive third-line therapy with cetuximab plus irinotecan bi-weekly until disease progression The primary study endpoint is ORR and the secondary study endpoints are PFS OS and drug safety
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