Ignite Creation Date:
2024-07-17 @ 10:44 AM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06490536
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-08
First Post:
2024-06-11
Brief Title:
The Sagittarius Trial
Sponsor:
IFOM ETS - The AIRC Institute of Molecular Oncology
Organization:
IFOM ETS - The AIRC Institute of Molecular Oncology
Study Overview
Official Title:
A Precision Medicine Trial Leveraging Blood-Based Tumor Genomics to Optimize Treatment in Operable Stage III and High-Risk Stage II Colon Cancer Patients
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:
Background Rationale
Colon cancer is a leading cause of cancer deaths with a high recurrence rate in stage II high-risk and stage III patients due to undetectable micro-metastases Liquid biopsy LB detects residual cancer DNA post-surgery and monitors treatment response
Primary Objective
Show that therapy based on tumor genetics and LB improves outcomes and quality of life for high-risk stage II and stage III colon cancer patients compared to conventional therapy
Secondary Objectives
Compare recurrence times Evaluate side effects and quality of life Assess cost differences Validate LB accuracy
Study Design Patients are randomized into standard or personalized treatment groups based on LB results
For positive LB results
Randomized to standard or customized therapy Monitor treatment response with LB
For negative LB results
Randomized to standard chemotherapy or follow-ups starting treatment if a positive result appears
Treatments
Standard Chemotherapy
CAPOX capecitabine and oxaliplatin FOLFOX folinic acid fluorouracil and oxaliplatin
Personalized Treatments
Customized chemotherapy with CAPOX Immunotherapy with nivolumab and ipilimumab Targeted therapy with trastuzumab and pertuzumab FOLFOX with anti-EGFR epidermal growth factor receptor therapy panitumumab
Population 700 patients with operable stage III and high-risk stage II colon cancer
Inclusion Criteria
Aged 18 or older Confirmed diagnosis Tumor tissue sample available
Exclusion Criteria
History of other tumors within five years Incomplete colonoscopy or recent polyp removal Metastatic disease or recent experimental study participation Major cardiovascular diseases intestinal obstruction autoimmune diseases neuropathy HIV Human Immunodeficiency Virus active TB Tuberculosis or hepatitis BC infection
Medical conditions contraindicating treatment
Endpoints
Primary
Evaluate disease recurrence after two years
Secondary
Assess disease recurrence and overall survival at 3 and 5 years Measure treatment safety and tolerability Validate LB accuracy Monitor quality of life using questionnaires
The study will last 5 years and be conducted in 25-30 hospitals across Italy Spain and Germany
Colon cancer is a leading cause of cancer deaths with a high recurrence rate in stage II high-risk and stage III patients due to undetectable micro-metastases Liquid biopsy LB detects residual cancer DNA post-surgery and monitors treatment response
Primary Objective
Show that therapy based on tumor genetics and LB improves outcomes and quality of life for high-risk stage II and stage III colon cancer patients compared to conventional therapy
Secondary Objectives
Compare recurrence times Evaluate side effects and quality of life Assess cost differences Validate LB accuracy
Study Design Patients are randomized into standard or personalized treatment groups based on LB results
For positive LB results
Randomized to standard or customized therapy Monitor treatment response with LB
For negative LB results
Randomized to standard chemotherapy or follow-ups starting treatment if a positive result appears
Treatments
Standard Chemotherapy
CAPOX capecitabine and oxaliplatin FOLFOX folinic acid fluorouracil and oxaliplatin
Personalized Treatments
Customized chemotherapy with CAPOX Immunotherapy with nivolumab and ipilimumab Targeted therapy with trastuzumab and pertuzumab FOLFOX with anti-EGFR epidermal growth factor receptor therapy panitumumab
Population 700 patients with operable stage III and high-risk stage II colon cancer
Inclusion Criteria
Aged 18 or older Confirmed diagnosis Tumor tissue sample available
Exclusion Criteria
History of other tumors within five years Incomplete colonoscopy or recent polyp removal Metastatic disease or recent experimental study participation Major cardiovascular diseases intestinal obstruction autoimmune diseases neuropathy HIV Human Immunodeficiency Virus active TB Tuberculosis or hepatitis BC infection
Medical conditions contraindicating treatment
Endpoints
Primary
Evaluate disease recurrence after two years
Secondary
Assess disease recurrence and overall survival at 3 and 5 years Measure treatment safety and tolerability Validate LB accuracy Monitor quality of life using questionnaires
The study will last 5 years and be conducted in 25-30 hospitals across Italy Spain and Germany
Detailed Description:
Background Rationale
Colon cancer CC is the second most lethal malignancy accounting for nearly 10 of all cancer-related deaths Despite over two-thirds of CC patients undergoing surgical resection 50 of stage III patients relapse within 5 years Adjuvant chemotherapy ACT typically involving oxaliplatin combined with a fluoropyrimidine offers only a 10-15 survival advantage over 5-fluorouracil alone The benefit from ACT is predicted by clinical and pathological parameters rather than metastatic propensity or biological sensitivity and its success is limited by high toxicity levels particularly oxaliplatin-induced peripheral sensory neuropathy
Liquid biopsy LB profiling circulating tumor DNA ctDNA has emerged as an effective diagnostic tool for early cancer detection staging prognosis monitoring drug resistance and detecting minimal residual disease MRD Retrospective studies show that ctDNA detection post-surgery and post-ACT is associated with high recurrence risk and worse recurrence-free survival RFS in stage I-III colorectal cancer CRC patients Prospective studies confirm ctDNAs prognostic value post-surgery and ACT
SAGITTARIUS Trial Objectives
Diagnosing MRD After Surgery Utilize post-surgical LB to identify high-risk tumors and stratify stage II high-risk and stage III CC patients enabling targeted treatments and reducing unnecessary chemotoxicity
Establishing the Efficacy of Adjuvant Chemotherapy and Targeted Therapies Tailor treatment based on the individual tumor genomic landscape to improve clinical outcomes and quality of life compared to conventional chemotherapy
Study Design
The SAGITTARIUS trial is a randomized phase III study designed to demonstrate the efficacy of ctDNA detection in guiding adjuvant clinical management of stage III and high-risk stage II CC patients The trial employs the CE-IVD marked tumor-informed MRD assay Signatera NATERA Inc and comprehensive tumor genomic profiling TruSight Oncology Comprehensive EU TSOComp Illumina Inc These tools will provide a detailed molecular genomic landscape of each patients tumor with results available within 8 weeks post-surgery for timely adjuvant treatment initiation
Patient Stratification and Randomization
Patients are stratified based on ctDNA status into two main trials
Trial-1 ctDNA Positive Patients Includes further stratification based on MSSMMRp extended RASRAF mutation status and MSI-HMMRd status Treatment arms include standard chemotherapy CAPOXFOLFOX or personalized treatments with reassessment of ctDNA status guiding subsequent therapies
Trial-2 ctDNA Negative Patients Patients are randomized to either a physician-choice chemotherapy regimen or intensive follow-up with interventional LBs at specified intervals
Therapeutic Approaches
Standard Chemotherapy Regimens CAPOX capecitabine and oxaliplatin and FOLFOX folinic acid fluorouracil and oxaliplatin
Personalized Therapies Include options such as FOLFIRI or TEMIRI for RASRAF-mutated tumors double immunotherapy nivolumab and ipilimumab for MSI-HMMRd anti-HER2 therapy trastuzumab and pertuzumab for HER2-amplified tumors and FOLFOX combined with anti-EGFR panitumumab for multiple wild-type tumors
Data Collection and Analysis
Data will be collected through regular clinical evaluations imaging studies and questionnaires to assess various endpoints including RFS overall survival treatment safety tolerability and quality of life The primary endpoint is the 2-year RFS in ctDNA positive patients while secondary endpoints include 3 and 5-year RFS overall survival and the accuracy of LB in detecting residual disease Statistical analyses will follow the intention-to-treat principle utilizing the Kaplan-Meier method for time-to-event data and stratified log-rank tests for comparison
Colon cancer CC is the second most lethal malignancy accounting for nearly 10 of all cancer-related deaths Despite over two-thirds of CC patients undergoing surgical resection 50 of stage III patients relapse within 5 years Adjuvant chemotherapy ACT typically involving oxaliplatin combined with a fluoropyrimidine offers only a 10-15 survival advantage over 5-fluorouracil alone The benefit from ACT is predicted by clinical and pathological parameters rather than metastatic propensity or biological sensitivity and its success is limited by high toxicity levels particularly oxaliplatin-induced peripheral sensory neuropathy
Liquid biopsy LB profiling circulating tumor DNA ctDNA has emerged as an effective diagnostic tool for early cancer detection staging prognosis monitoring drug resistance and detecting minimal residual disease MRD Retrospective studies show that ctDNA detection post-surgery and post-ACT is associated with high recurrence risk and worse recurrence-free survival RFS in stage I-III colorectal cancer CRC patients Prospective studies confirm ctDNAs prognostic value post-surgery and ACT
SAGITTARIUS Trial Objectives
Diagnosing MRD After Surgery Utilize post-surgical LB to identify high-risk tumors and stratify stage II high-risk and stage III CC patients enabling targeted treatments and reducing unnecessary chemotoxicity
Establishing the Efficacy of Adjuvant Chemotherapy and Targeted Therapies Tailor treatment based on the individual tumor genomic landscape to improve clinical outcomes and quality of life compared to conventional chemotherapy
Study Design
The SAGITTARIUS trial is a randomized phase III study designed to demonstrate the efficacy of ctDNA detection in guiding adjuvant clinical management of stage III and high-risk stage II CC patients The trial employs the CE-IVD marked tumor-informed MRD assay Signatera NATERA Inc and comprehensive tumor genomic profiling TruSight Oncology Comprehensive EU TSOComp Illumina Inc These tools will provide a detailed molecular genomic landscape of each patients tumor with results available within 8 weeks post-surgery for timely adjuvant treatment initiation
Patient Stratification and Randomization
Patients are stratified based on ctDNA status into two main trials
Trial-1 ctDNA Positive Patients Includes further stratification based on MSSMMRp extended RASRAF mutation status and MSI-HMMRd status Treatment arms include standard chemotherapy CAPOXFOLFOX or personalized treatments with reassessment of ctDNA status guiding subsequent therapies
Trial-2 ctDNA Negative Patients Patients are randomized to either a physician-choice chemotherapy regimen or intensive follow-up with interventional LBs at specified intervals
Therapeutic Approaches
Standard Chemotherapy Regimens CAPOX capecitabine and oxaliplatin and FOLFOX folinic acid fluorouracil and oxaliplatin
Personalized Therapies Include options such as FOLFIRI or TEMIRI for RASRAF-mutated tumors double immunotherapy nivolumab and ipilimumab for MSI-HMMRd anti-HER2 therapy trastuzumab and pertuzumab for HER2-amplified tumors and FOLFOX combined with anti-EGFR panitumumab for multiple wild-type tumors
Data Collection and Analysis
Data will be collected through regular clinical evaluations imaging studies and questionnaires to assess various endpoints including RFS overall survival treatment safety tolerability and quality of life The primary endpoint is the 2-year RFS in ctDNA positive patients while secondary endpoints include 3 and 5-year RFS overall survival and the accuracy of LB in detecting residual disease Statistical analyses will follow the intention-to-treat principle utilizing the Kaplan-Meier method for time-to-event data and stratified log-rank tests for comparison
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None