Ignite Creation Date:
2024-07-17 @ 11:41 AM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06491355
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-09
First Post:
2024-06-25
Brief Title:
First-Line Treatment Induced With mFOLFOX6 and HLX04 Regimen Following Combined With Serplulimab in MSS Initially Unresectable Metastatic Colorectal Cancer
Sponsor:
Sir Run Run Shaw Hospital
Organization:
Sir Run Run Shaw Hospital
Study Overview
Official Title:
Efficacy and Safety of First-Line Treatment Induced With mFOLFOX6 and HLX04 Regimen Following Combined With Serplulimab in MSS Initially Unresectable Metastatic Colorectal Cancer A Prospective Multicenter Randomized Controlled Trial ASTRUM-IUmCRC
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
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 prospective multi-center randomized controlled clinical intervention study aiming to explore the effectiveness and safety of mfolfox6 and hlx04 regimens combined with slulimumab as first-line treatment for MSS-type initial unresectable metastatic colorectal cancer after induction therapy This study plans to include a total of 72 patients with untreated MSS-type initial unresectable metastatic colorectal cancer
This study randomly allocated groups through a randomization system and entered the following treatment groups at a ratio of 11 1 Experimental group mfolfox6 and hlx04 regimen induction therapy followed by slulimab treatment 36 cases 2 Control group Group mfolfox6 and hlx04 regimen treatment 36 cases
This study randomly allocated groups through a randomization system and entered the following treatment groups at a ratio of 11 1 Experimental group mfolfox6 and hlx04 regimen induction therapy followed by slulimab treatment 36 cases 2 Control group Group mfolfox6 and hlx04 regimen treatment 36 cases
Detailed Description:
Colorectal Cancer CRC is a common malignant tumor Its incidence ranks third and second among men and women respectively and its mortality rate ranks third Data from the World Health Organizations International Agency for Research on Cancer IARC in 2020 show that more than 930000 patients died due to CRC Since 2000 the incidence and mortality of colorectal cancer have been steadily increasing in China The National Cancer Center of China NCC reported that there were approximately 408000 new cases of CRC in China in 2016 and approximately 196000 deaths Most of the patients are in the mid-to-late stage when diagnosed and about 35 of them are in the advanced stage They have no chance of radical surgery and can only receive palliative care
In the early days when leucovorin LV and 5-fluorouracil 5-FU were used as the main treatment options for patients with metastatic colorectal cancer mCRC the efficacy was poor and the median overall survival OS of patients was only for 8-12 months Since the introduction of effective cytotoxic drugs such as irinotecan and oxaliplatin in 2000 the combination regimens FOLFOX 5-FULV oxaliplatin and FOLFIRI 5-FULV irinotecan have become first-line systemic Standard protocol in treatment The use of biologics targeting key pathways in the development and progression of mCRC such as epidermal growth factor receptor EGFR and vascular endothelial growth factor VEGF-related pathways further extends the survival of mCRC patients
In the latest version of CSCO colorectal cancer diagnosis and treatment guidelines the main recommended first-line treatments are FOLFOXFOLFIRIbevacizumab or cetuximab both RAS and BRAF are wild-type FOLFOXFOLFIRIbevacizumab RAS or BRAF mutant
PD-1 plays an important role in suppressing immune responses and promoting immune tolerance by inhibiting the activity of T cells allowing cancer cells to evade immune surveillance Cells in the tumor microenvironment often express PD-1 and PD-L1 Consistent with the inducible expression of PD-L1 by tumor cells activated CD8 effector T cells often express PD-1 indicating that tumor cells are resistant to adaptive immune responses PD-L1 has been found to be expressed in many types of cancer including melanoma lung cancer urothelial cancer and hepatocellular carcinoma Its expression can also be induced by various factors such as radiation which helps cancer cells evade immune regulation Blocking the PD-1PD-L1 interaction has been shown to treat a variety of cancers Clinical studies have proven that anti-PD-1 and anti-PD-L1 monoclonal antibodies can induce long-lasting anti-tumor activity against a variety of tumors Anti-PD-1 monoclonal antibodies have been approved for the treatment of melanoma non-small cell lung cancer small cell lung cancer head and neck squamous cell carcinoma urothelial carcinoma entities with high microsatellite instability or mismatch repair deficiency and colorectal cancer gastric cancer esophageal cancer cervical cancer hepatocellular carcinoma HCC Merkel cell carcinoma MCC renal cell carcinoma endometrial cancer bladder cancer primary mediastinal large B-cell lymphoma PMBCL and classic Hodgkin lymphoma A large number of clinical studies of anti-PD-1 antibodies are currently underway some as monotherapy and some in combination with multiple drugs
This study is an open-label single-arm phase II clinical trial The study inclusion criteria are patients with unresectable mCRC aged 18-75 years old and histologically confirmed by multidisciplinary treatment MDT The patients have RAS gene mutations and are confirmed to be MSS state All patients received treatment with sintilimab combined with CapeOx and bevacizumab After the disease achieved complete response CRpartial response PRstable disease SD maintenance treatment was performed The main purpose of the study Endpoints include objective response rate ORR as assessed by RECIST v11 and adverse events as assessed by CTCAE v50 The secondary endpoint is progression-free survival PFS
This study mainly aims to explore the effectiveness of chemotherapy and bevacizumab induction therapy combined with PD-1 monoclonal antibody in the first-line treatment of MSS-type initial unresectable metastatic colorectal cancer The second is its safety and tolerability
In the early days when leucovorin LV and 5-fluorouracil 5-FU were used as the main treatment options for patients with metastatic colorectal cancer mCRC the efficacy was poor and the median overall survival OS of patients was only for 8-12 months Since the introduction of effective cytotoxic drugs such as irinotecan and oxaliplatin in 2000 the combination regimens FOLFOX 5-FULV oxaliplatin and FOLFIRI 5-FULV irinotecan have become first-line systemic Standard protocol in treatment The use of biologics targeting key pathways in the development and progression of mCRC such as epidermal growth factor receptor EGFR and vascular endothelial growth factor VEGF-related pathways further extends the survival of mCRC patients
In the latest version of CSCO colorectal cancer diagnosis and treatment guidelines the main recommended first-line treatments are FOLFOXFOLFIRIbevacizumab or cetuximab both RAS and BRAF are wild-type FOLFOXFOLFIRIbevacizumab RAS or BRAF mutant
PD-1 plays an important role in suppressing immune responses and promoting immune tolerance by inhibiting the activity of T cells allowing cancer cells to evade immune surveillance Cells in the tumor microenvironment often express PD-1 and PD-L1 Consistent with the inducible expression of PD-L1 by tumor cells activated CD8 effector T cells often express PD-1 indicating that tumor cells are resistant to adaptive immune responses PD-L1 has been found to be expressed in many types of cancer including melanoma lung cancer urothelial cancer and hepatocellular carcinoma Its expression can also be induced by various factors such as radiation which helps cancer cells evade immune regulation Blocking the PD-1PD-L1 interaction has been shown to treat a variety of cancers Clinical studies have proven that anti-PD-1 and anti-PD-L1 monoclonal antibodies can induce long-lasting anti-tumor activity against a variety of tumors Anti-PD-1 monoclonal antibodies have been approved for the treatment of melanoma non-small cell lung cancer small cell lung cancer head and neck squamous cell carcinoma urothelial carcinoma entities with high microsatellite instability or mismatch repair deficiency and colorectal cancer gastric cancer esophageal cancer cervical cancer hepatocellular carcinoma HCC Merkel cell carcinoma MCC renal cell carcinoma endometrial cancer bladder cancer primary mediastinal large B-cell lymphoma PMBCL and classic Hodgkin lymphoma A large number of clinical studies of anti-PD-1 antibodies are currently underway some as monotherapy and some in combination with multiple drugs
This study is an open-label single-arm phase II clinical trial The study inclusion criteria are patients with unresectable mCRC aged 18-75 years old and histologically confirmed by multidisciplinary treatment MDT The patients have RAS gene mutations and are confirmed to be MSS state All patients received treatment with sintilimab combined with CapeOx and bevacizumab After the disease achieved complete response CRpartial response PRstable disease SD maintenance treatment was performed The main purpose of the study Endpoints include objective response rate ORR as assessed by RECIST v11 and adverse events as assessed by CTCAE v50 The secondary endpoint is progression-free survival PFS
This study mainly aims to explore the effectiveness of chemotherapy and bevacizumab induction therapy combined with PD-1 monoclonal antibody in the first-line treatment of MSS-type initial unresectable metastatic colorectal cancer The second is its safety and tolerability
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