The Sagittarius Trial
- Registration Number
- NCT06490536
- 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:
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- Detailed Description
Background \& Rationale:
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Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 700
- SAGITTARIUS trial written informed consent.
- Age ≥ 18 years.
- Histologically confirmed diagnosis of operable stage III and High-Risk stage II CC located at least 12 cm from the anal verge by endoscopy and above the peritoneal reflection at surgery.
- Availability of the original FFPE tumor tissue.
- ECOG performance status 0-1.
- Normal organ functions (as defined in section 9.3).
- Women with childbearing potential (WOCBP) should complete a pregnancy test and be willing to use highly effective contraceptive methods.
- History of another neoplastic disease, unless in remission for ≥ 5 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- Had an incomplete diagnostic colonoscopy.
- Recent polyps' removal (within one month).
- Macroscopic or microscopic evidence of residual tumor (R1 or R2 resections). Patients should never have had any evidence of metastatic disease (including presence of tumor cells in the peritoneal lavage).
- Current or recent treatment with another investigational drug or participation in another investigational study.
- Patient unable to comply with the study protocol owing to psychological, social or geographical reasons.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
- Inadequate contraception (male or female patients) if of childbearing or procreational potential.
- Clinically relevant cardiovascular disease.
- Acute or subacute intestinal occlusion or history of inflammatory bowel disease or any other autoimmune disease.
- Pre-existing neuropathy > grade 1. Known grade 3 or 4 allergic reaction to any of the components of the treatment.
- Has a known DPD (DihydroPyrimidine Dehydrogenase) deficiency.
- Has a known Gilbert Syndrome or UGT1A1 homozygous *28/*28 germline variant.
- Has a known history of Human Immunodeficiency Virus (HIV).
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus infection.
- Has a known history of active TB (Bacillus Tuberculosis).
- Has a medical condition that contraindicate the use of the investigational medicinal product (IMP) according to product indications.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Trial-1 (ctDNA+) Strata-1 (MSS/MMRp extendend RAS/RAFmut) Standard Therapy Oxaliplatin CAPOX/FOLFOX for 6 months or until toxicity Trial-1 (ctDNA+) Strata-1 (MSS/MMRp extendend RAS/RAFmut) Standard Therapy Capecitabine CAPOX/FOLFOX for 6 months or until toxicity Trial-1 (ctDNA+) Strata-1 (MSS/MMRp extendend RAS/RAFmut) Standard Therapy Fluorouracil CAPOX/FOLFOX for 6 months or until toxicity Trial-1 (ctDNA+) Strata-1 (MSS/MMRp extendend RAS/RAFmut) Standard Therapy Folinic acid CAPOX/FOLFOX for 6 months or until toxicity Trial-1 (ctDNA+) Strata-1 (MSS/MMRp extendend RAS/RAFmut) Tailored Therapy Oxaliplatin 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. Trial-1 (ctDNA+) Strata-1 (MSS/MMRp extendend RAS/RAFmut) Tailored Therapy Folinic acid 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. Trial-1 (ctDNA+) Strata-1 (MSS/MMRp extendend RAS/RAFmut) Tailored Therapy Capecitabine 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. Trial-1 (ctDNA+) Strata-1 (MSS/MMRp extendend RAS/RAFmut) Tailored Therapy Fluorouracil 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. Trial-1 (ctDNA+) Strata-1 (MSS/MMRp extendend RAS/RAFmut) Tailored Therapy Temozolomide 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. Trial-1 (ctDNA+) Strata-1 (MSS/MMRp extendend RAS/RAFmut) Tailored Therapy Irinotecan 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. Trial-1 (ctDNA+) Strata-2 (MSI-H/MMRd & MSS/MMRp extended RAS/RAFwt) Standard Therapy Oxaliplatin CAPOX/FOLFOX for 6 months or until toxicity Trial-1 (ctDNA+) Strata-2 (MSI-H/MMRd & MSS/MMRp extended RAS/RAFwt) Standard Therapy Capecitabine CAPOX/FOLFOX for 6 months or until toxicity Trial-1 (ctDNA+) Strata-2 (MSI-H/MMRd & MSS/MMRp extended RAS/RAFwt) Standard Therapy Folinic acid CAPOX/FOLFOX for 6 months or until toxicity Trial-1 (ctDNA+) Strata-2 (MSI-H/MMRd & MSS/MMRp extended RAS/RAFwt) Standard Therapy Fluorouracil CAPOX/FOLFOX for 6 months or until toxicity Trial-1 (ctDNA+) Strata-2 (MSI-H/MMRd & MSS/MMRp extended RAS/RAFwt) Tailored Therapy Nivolumab 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. Trial-1 (ctDNA+) Strata-2 (MSI-H/MMRd & MSS/MMRp extended RAS/RAFwt) Tailored Therapy Trastuzumab 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. Trial-1 (ctDNA+) Strata-2 (MSI-H/MMRd & MSS/MMRp extended RAS/RAFwt) Tailored Therapy Ipilimumab 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. Trial-1 (ctDNA+) Strata-2 (MSI-H/MMRd & MSS/MMRp extended RAS/RAFwt) Tailored Therapy Pertuzumab 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. Trial-1 (ctDNA+) Strata-2 (MSI-H/MMRd & MSS/MMRp extended RAS/RAFwt) Tailored Therapy Panitumumab 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. Trial-2 (ctDNA-) Standard Therapy Oxaliplatin Chemotherapy regimen at prior declared physician choice (CAPE/CAPOX/FOLFOX/5-FU±LV). Trial-2 (ctDNA-) Standard Therapy Capecitabine Chemotherapy regimen at prior declared physician choice (CAPE/CAPOX/FOLFOX/5-FU±LV). Trial-2 (ctDNA-) Standard Therapy Folinic acid Chemotherapy regimen at prior declared physician choice (CAPE/CAPOX/FOLFOX/5-FU±LV). Trial-2 (ctDNA-) Standard Therapy Fluorouracil Chemotherapy regimen at prior declared physician choice (CAPE/CAPOX/FOLFOX/5-FU±LV).
- Primary Outcome Measures
Name Time Method 2-Year Recurrence-Free Survival (RFS) Assessed at 2 years post-surgery The primary outcome measure is the 2-year recurrence-free survival (RFS) rate, defined as the proportion of patients who remain free of disease recurrence two years after surgery. This metric is assessed using regular clinical evaluations and imaging studies. Recurrence is determined by the reappearance of colon cancer as confirmed by histological, radiologi...
- Secondary Outcome Measures
Name Time Method 3-Year Recurrence-Free Survival (RFS) Assessed at 3 years post-surgery The secondary outcome measure is the 3-year recurrence-free survival (RFS) rate, defined as the proportion of patients who remain free of disease recurrence three years after surgery. This metric is assessed using regular clinical evaluations and imaging studies. Recurrence is determined by the reappearance of colon cancer as confirmed by histological, radio...
Treatment Safety and Tolerability Assessed throughout the treatment period, up to 6 months This secondary outcome measure evaluates the safety and tolerability of the treatments, including both standard and personalized therapies. It involves recording and analyzing the incidence, severity, and type of adverse events experienced by patients during the treatment period, using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Assessment of Quality of Life Using FACT-C Questionnaire Assessed at regular intervals during the treatment period and during follow-up, up to 3 years or up to the date of first documented progression or the date of consent withdrawal This secondary outcome measure evaluates the impact of treatment on patients' quality of life specific to colorectal cancer using the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) questionnaire. The FACT-C assesses quality of life across physical, social/family, emotional, and functional well-being domains. The questionnaire provides a score ba...
Assessment of Quality of Life Using EQ-5D-5L Questionnaire Assessed at regular intervals during the treatment period and during follow-up, up to 3 years or up to the date of first documented progression or the date of consent withdrawal This secondary outcome measure evaluates the impact of treatment on patients' quality of life across five dimensions using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire. The EQ-5D-5L evaluates quality of life in mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a scale from 1 to 5, with 1 in...
5-Year Overall Survival (OS) Assessed at 5 years post-surgery The secondary outcome measure is the 5-year overall survival (OS) rate, defined as the proportion of patients who are alive five years after surgery, regardless of disease status. This metric is assessed using regular clinical evaluations and follow-ups.
Sensitivity and Specificity of Liquid Biopsy in Detecting Residual Disease Assessed at regular intervals post-surgery, up to 2 years This outcome measure evaluates the effectiveness of liquid biopsy in detecting residual disease by comparing its results with traditional imaging techniques (CT scans, MRIs) and clinical findings. Sensitivity will be measured by the ability of liquid biopsy to correctly identify patients with residual disease, expressed as a percentage of positive results co...
Trial Locations
- Locations (14)
Istituto Clinico Humanitas
🇮🇹Rozzano, Milano, Italy
Istituto di Candiolo
🇮🇹Candiolo, Torino, Italy
Azienda Sanitaria Locale di Biella
🇮🇹Biella, Italy
Azienda Ospedaliera Universitaria San Martino
🇮🇹Genova, Italy
Fondazione Poliambulanza
🇮🇹Brescia, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Ospedale Niguarda
🇮🇹Milan, Italy
Ospedale Maggiore di Novara
🇮🇹Novara, Italy
Azienda Ospedaliera Universitaria di Parma
🇮🇹Parma, Italy
Ospedale Santa Maria della Misericordia
🇮🇹Perugia, Italy
Azienda Unità Sanitaria Locale della Romagna
🇮🇹Ravenna, Italy
Policlinico Universitario Gemelli
🇮🇹Roma, Italy
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain