The Sagittarius Trial

Sponsor
IFOM ETS - The AIRC Institute of Molecular Oncology
Study ID
NCT06490536
Phase
PHASE3
Status
Recruiting
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Conditions

  • Colon Cancer Stage II
  • Colon Cancer Stage III

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Oxaliplatin — DRUG
    Oxaliplatin is used as part of the chemotherapy regimens for patients with ctDNA+ results in the SAGITTARIUS trial. It is administered in the following ways: CAPOX Regimen: Oxaliplatin 130 mg/m² is given intravenously on day 1, in combination with capecitabine 1000 mg/m² taken orally twice daily on days 1-14 of each 21-day cycle. FOLFOX Regimen: Oxaliplatin 85 mg/m² is administered intravenously on day 1, alongside folinic acid 400 mg/m² and fluorouracil 400 mg/m² IV bolus, followed by 2400 mg/m² IV infusion over 46 hours, in each 14-day cycle. Dosages are standardized, while the duration of treatment can be adjusted based on patient response and liquid biopsy results, typically up to 6 months.
  • Capecitabine — DRUG
    Capecitabine is used as part of the chemotherapy regimens for patients with ctDNA+ and ctDNA- results in the SAGITTARIUS trial. It is administered in the following ways: CAPOX Regimen: Capecitabine 1000 mg/m² is taken orally twice daily on days 1-14 of each 21-day cycle, in combination with oxaliplatin 130 mg/m² given intravenously on day 1. Capecitabine Monotherapy for High-Risk ctDNA- Patients: Capecitabine 1250 mg/m² is taken orally twice daily on days 1-14 of each 21-day cycle for patients identified as high-risk but with negative ctDNA results. The dosage of capecitabine is standardized, while the duration of treatment varies based on patient response and monitoring results, typically up to 6 months.
  • Folinic acid — DRUG
    Folinic acid is used as part of the FOLFOX chemotherapy regimen for patients with ctDNA+ results in the SAGITTARIUS trial. It is administered in the following way: FOLFOX Regimen: Folinic acid (leucovorin) 400 mg/m² is given intravenously on day 1, in combination with oxaliplatin 85 mg/m² IV on day 1 and fluorouracil 400 mg/m² IV bolus followed by 2400 mg/m² IV infusion over 46 hours, in each 14-day cycle. The dosage of folinic acid is standardized, while the duration of treatment can be adjusted based on patient response and liquid biopsy results, typically up to 6 months.
  • Fluorouracil — DRUG
    Fluorouracil is used as part of the FOLFOX chemotherapy regimen for patients with ctDNA+ results in the SAGITTARIUS trial. It is administered in the following way: FOLFOX Regimen: Fluorouracil 400 mg/m² is given as an intravenous (IV) bolus on day 1, followed by 2400 mg/m² as a continuous IV infusion over 46 hours, in combination with folinic acid (leucovorin) 400 mg/m² IV on day 1 and oxaliplatin 85 mg/m² IV on day 1. This regimen is repeated every 14 days. The dosage of fluorouracil is standardized, while the duration of treatment is typically up to 6 months, adjusted based on patient response and liquid biopsy results.
  • Temozolomide — DRUG
    Temozolomide is used as part of the tailored chemotherapy regimen for patients with ctDNA+ results in the SAGITTARIUS trial, specifically for those with MGMT-negative tumors. It is administered in the following way: TEMIRI Regimen: Temozolomide 150-200 mg/m² is taken orally once daily on days 1-5 of each 28-day cycle, in combination with irinotecan 250 mg/m² administered intravenously on day 1 of each cycle. The dosage of temozolomide is standardized, while the duration of treatment can be adjusted based on patient response and liquid biopsy results.
  • Irinotecan — DRUG
    Irinotecan is used as part of the tailored chemotherapy regimen for patients with ctDNA+ results in the SAGITTARIUS trial. It is administered in the following ways: TEMIRI Regimen: Irinotecan 250 mg/m² is administered intravenously on day 1 of each 28-day cycle, in combination with temozolomide 150-200 mg/m² taken orally once daily on days 1-5. FOLFIRI Regimen: Irinotecan 180 mg/m² is given intravenously on day 1, in combination with folinic acid (leucovorin) 400 mg/m² IV, fluorouracil 400 mg/m² IV bolus, followed by 2400 mg/m² IV infusion over 46 hours, in each 14-day cycle. The dosage of irinotecan is standardized, while the duration of treatment can be adjusted based on patient response and liquid biopsy results.
  • Nivolumab — DRUG
    Nivolumab is used as part of the tailored immunotherapy regimen for patients with ctDNA+ results, specifically for those with MSI-H/MMRd tumors in the SAGITTARIUS trial. It is administered in the following way: Nivolumab: 3 mg/kg is given intravenously every 2 weeks. This dosage is standardized, while the duration of treatment can be adjusted based on patient response and liquid biopsy results.
  • Ipilimumab — DRUG
    Ipilimumab is used as part of the tailored immunotherapy regimen for patients with ctDNA+ results, specifically for those with MSI-H/MMRd tumors in the SAGITTARIUS trial. It is administered in the following way: Ipilimumab: 1 mg/kg is given intravenously every 6 weeks. This dosage is standardized, while the duration of treatment can be adjusted based on patient response and liquid biopsy results.
  • Trastuzumab — DRUG
    Trastuzumab is used as part of the tailored targeted therapy regimen for patients with ctDNA+ results, specifically for those with HER2-amplified tumors in the SAGITTARIUS trial. It is administered in the following way: Trastuzumab: 8 mg/kg as an initial intravenous (IV) loading dose, followed by 6 mg/kg IV every 3 weeks. The dosage is standardized, while the duration of treatment can be adjusted based on patient response and liquid biopsy results.
  • Pertuzumab — DRUG
    Pertuzumab is used as part of the tailored targeted therapy regimen for patients with ctDNA+ results, specifically for those with HER2-amplified tumors in the SAGITTARIUS trial. It is administered in the following way: Pertuzumab: 840 mg as an initial intravenous (IV) loading dose, followed by 420 mg IV every 3 weeks. The dosage is standardized, while the duration of treatment can be adjusted based on patient response and liquid biopsy results.
  • Panitumumab — DRUG
    Panitumumab is used as part of the tailored targeted therapy regimen for patients with ctDNA+ results, specifically for those with multiple wild-type tumors (MSS/MMRp extended RAS/RAF wild-type) in the SAGITTARIUS trial. It is administered in the following way: Panitumumab: 6 mg/kg is given intravenously every 2 weeks. The dosage is standardized, while the duration of treatment can be adjusted based on patient response and liquid biopsy results.

Study Details

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. Metastatic disease or recent experimental study participation. Major cardiovascular diseases, intestinal obstruction, autoimmune diseases, neuropathy, HIV (Human Immunodeficiency Virus), active TB (Tuberculosis), or hepatitis B/C infection. Medical conditions contraindicating treatment. Prior neoadjuvant treatment administered before surgery. 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.

Key Dates

Start date
Oct 22, 2024
Status verified
Aug 2025
Primary completion
Mar 1, 2026
Completion
Sep 1, 2028

Study Design

Enrollment
700 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Trial-1 (ctDNA+) Strata-1 (MSS/MMRp extendend RAS/RAFmut) Standard Therapy
    CAPOX/FOLFOX for 6 months or until toxicity
  • Experimental: Trial-1 (ctDNA+) Strata-1 (MSS/MMRp extendend RAS/RAFmut) Tailored Therapy
    CAPOX for 3 months with an interventional liquid biopsy at the end of the treatment. Patients still resulting ctDNA+ will be switched to a tailored therapy (FOLFIRI for RAS/RAF-mutated and MGMT-positive tumors or TEMIRI for RAS/RAF-mutated and MGMT-negative tumors) for 6 months or until toxicity. On the other hand, ctDNA- patients will continue CAPOX up to 3 months, and their ctDNA status will be re-assessed at the end of the treatment. Patients remaining ctDNA- will enter into follow-up, while patients resulting ctDNA+ will be switched to the tailored therapy.
  • Active Comparator: Trial-1 (ctDNA+) Strata-2 (MSI-H/MMRd & MSS/MMRp extended RAS/RAFwt) Standard Therapy
    CAPOX/FOLFOX for 6 months or until toxicity
  • Experimental: Trial-1 (ctDNA+) Strata-2 (MSI-H/MMRd & MSS/MMRp extended RAS/RAFwt) Tailored Therapy
    Tailored therapy (nivolumab+ipilimumab for MSI-H/MMRd: MSI-H/MMRd tumors and MSS/MMRp tumors with POLE mutations and a high TMB or trastuzumab + pertuzumab for MSS/MMRp HER2-amplified tumors or panitumumab+folfox for MSS/MMRp RAS/RAF/HER2 wild-type) for 3 months, at the end, the ctDNA status of patients will be reassessed to further guide their subsequent treatments. Patients still ctDNA+ at will be switched to standard therapy. On the other hand, patients undergoing seroconversion will continue the same therapy for 3 further months and will be then re-assessed at the end of the treatment. Patients resulting ctDNA- will enter into Follow-up, while patients resulting ctDNA+ will be switched to the standard therapy.
  • Active Comparator: Trial-2 (ctDNA-) Standard Therapy
    Chemotherapy regimen at prior declared physician choice (CAPE/CAPOX/FOLFOX/5-FU±LV).
  • No Intervention: Trial-2 (ctDNA-) Intensive Follow-up
    Intensive follow-up for 6 months (except for MSS Stage III High-risk patients which will be treated with CAPE).

Primary Outcome Measure

2-Year Recurrence-Free Survival (RFS) [ Time Frame: Assessed at 2 years post-surgery ]

Central Contacts

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