Ignite Creation Date:
2024-10-26 @ 3:39 PM
Last Modification Date:
2024-10-26 @ 3:39 PM
Study NCT ID:
NCT06575127
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-08-25
Brief Title:
Modified FOLFOXIRI Plus Target Therapy as a First Line Treatment for Advanced Colorectal Cancer a Prospective Phase Two Study
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Modified FOLFOXIRI Plus Target Therapy as a First Line Treatment for Advanced Colorectal Cancer a Prospective Phase Two Study
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This prospective Phase II study aims to evaluate the efficacy and safety of a modified FOLFOXIRI regimen in the treatment of metastatic colorectal cancer MCRC FOLFOXIRI though effective is known for its high toxicity necessitating close monitoring and dose adjustments
The primary endpoint is to assess the impact on the objective response rate and evaluate both acute and delayed toxicity The secondary endpoints include studying the treatments effectiveness as conversion therapy along with disease-free survival DFS and overall survival OS The tertiary endpoint focuses on evaluating predictive and prognostic factors of significance
This study seeks to balance the efficacy of FOLFOXIRI with a modified dose to minimize toxicity while maintaining therapeutic benefits providing a potentially safer and effective option for patients with MCRC
The primary endpoint is to assess the impact on the objective response rate and evaluate both acute and delayed toxicity The secondary endpoints include studying the treatments effectiveness as conversion therapy along with disease-free survival DFS and overall survival OS The tertiary endpoint focuses on evaluating predictive and prognostic factors of significance
This study seeks to balance the efficacy of FOLFOXIRI with a modified dose to minimize toxicity while maintaining therapeutic benefits providing a potentially safer and effective option for patients with MCRC
Detailed Description:
This prospective Phase II clinical trial aims to assess the efficacy and safety of a modified dose regimen of FOLFOXIRI in the treatment of metastatic colorectal cancer MCRC FOLFOXIRI is a chemotherapy regimen known for its high toxicity necessitating close monitoring dose reductions and supportive treatments While previous studies have demonstrated the clinical efficacy of FOLFOXIRI compared to FOLIRI or FOLFOX the regimens toxicity remains a significant concern
Intervention
Modified FOLFOXIRI Regimen
Oxaliplatin 85 mgm² IV over 2 hours Day 1 Irinotecan 150 mgm² IV over 90 minutes Day 1 5-FU 2400 mgm² IV over 48 hours infusion Day 1
Targeted Therapy
KRASNRASBRAF Wild-Type Left-Sided Tumor Anti-EGFR treatment with either Panitumumab 6 mgkg IV over 60 minutes Day 1 or Cetuximab 500 mgm² IV Day 1
KRASNRAS Mutant or Right-Sided Tumor Bevacizumab 5 mgkg IV over 30-90 minutes Day 1
Treatment Schedule Administered biweekly for a maximum of 12 cycles 6 months
G-CSF Prophylaxis Administered as primary prophylaxis for patients older than 55 and as secondary prophylaxis for those who develop grade 3 neutropenia
Dose Modifications and Treatment-Related Toxicity
Toxicity will be evaluated after each cycle using the Common Toxicity Criteria for Adverse Events CTCAE version 50 National Cancer Institute 2017
Dose Reduction Guidelines A 25 dose reduction will be implemented for specific grade IIIIV acute toxicities including neutropenia febrile neutropenia thrombocytopenia diarrhea mucositisstomatitis hand-foot syndrome peripheral neuropathy elevated liver enzymes severe fatigue hypertension proteinuria and dermatologic toxicity
Treatment Discontinuation Patients who experience further grade IIIIV acute toxicity after dose reduction will be excluded from the study
Treatment Duration
Eligible for Surgery Patients with a favorable response will receive a maximum of 8 cycles before surgical evaluation
Ineligible for Surgery Treatment will continue until the completion of 12 cycles intolerable toxicity or a maximum duration of 6 months
Assessments
Disease Assessment Performed every 4 cycles 8 weeks during the induction phase followed by every 3 months Quality of life will be evaluated using the EORTC QLQ C30 and CR 29 questionnaires
Response Assessment Based on RECIST v11 criteria categorized as Complete Response CR Partial Response PR Stable Disease SD or Progressive Disease PD
Statistical Analysis
Survival Analysis Kaplan-Meier estimates with one-sided log-rank tests will be used to analyze progression-free survival PFS Overall survival OS will be calculated from the date of histological diagnosis to the date of last follow-up or death
Data Analysis Data will be analyzed using IBM SPSS version 26 Quantitative data will be presented as means standard deviations and ranges or as medians with interquartile ranges depending on distribution Qualitative data will be presented as frequencies and percentages Chi-square tests will compare groups with qualitative data The confidence interval is set at 95 with a significance threshold of p 005
Intervention
Modified FOLFOXIRI Regimen
Oxaliplatin 85 mgm² IV over 2 hours Day 1 Irinotecan 150 mgm² IV over 90 minutes Day 1 5-FU 2400 mgm² IV over 48 hours infusion Day 1
Targeted Therapy
KRASNRASBRAF Wild-Type Left-Sided Tumor Anti-EGFR treatment with either Panitumumab 6 mgkg IV over 60 minutes Day 1 or Cetuximab 500 mgm² IV Day 1
KRASNRAS Mutant or Right-Sided Tumor Bevacizumab 5 mgkg IV over 30-90 minutes Day 1
Treatment Schedule Administered biweekly for a maximum of 12 cycles 6 months
G-CSF Prophylaxis Administered as primary prophylaxis for patients older than 55 and as secondary prophylaxis for those who develop grade 3 neutropenia
Dose Modifications and Treatment-Related Toxicity
Toxicity will be evaluated after each cycle using the Common Toxicity Criteria for Adverse Events CTCAE version 50 National Cancer Institute 2017
Dose Reduction Guidelines A 25 dose reduction will be implemented for specific grade IIIIV acute toxicities including neutropenia febrile neutropenia thrombocytopenia diarrhea mucositisstomatitis hand-foot syndrome peripheral neuropathy elevated liver enzymes severe fatigue hypertension proteinuria and dermatologic toxicity
Treatment Discontinuation Patients who experience further grade IIIIV acute toxicity after dose reduction will be excluded from the study
Treatment Duration
Eligible for Surgery Patients with a favorable response will receive a maximum of 8 cycles before surgical evaluation
Ineligible for Surgery Treatment will continue until the completion of 12 cycles intolerable toxicity or a maximum duration of 6 months
Assessments
Disease Assessment Performed every 4 cycles 8 weeks during the induction phase followed by every 3 months Quality of life will be evaluated using the EORTC QLQ C30 and CR 29 questionnaires
Response Assessment Based on RECIST v11 criteria categorized as Complete Response CR Partial Response PR Stable Disease SD or Progressive Disease PD
Statistical Analysis
Survival Analysis Kaplan-Meier estimates with one-sided log-rank tests will be used to analyze progression-free survival PFS Overall survival OS will be calculated from the date of histological diagnosis to the date of last follow-up or death
Data Analysis Data will be analyzed using IBM SPSS version 26 Quantitative data will be presented as means standard deviations and ranges or as medians with interquartile ranges depending on distribution Qualitative data will be presented as frequencies and percentages Chi-square tests will compare groups with qualitative data The confidence interval is set at 95 with a significance threshold of p 005
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