The Sagittarius Trial
NCT Number: NCT06490536
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Colon Cancer Stage II|Colon Cancer Stage III
Interventions: DRUG: Oxaliplatin|DRUG: Capecitabine|DRUG: Folinic acid|DRUG: Fluorouracil|DRUG: Temozolomide|DRUG: Irinotecan|DRUG: Nivolumab|DRUG: Ipilimumab|DRUG: Trastuzumab|DRUG: Pertuzumab|DRUG: Panitumumab
Sponsor: IFOM ETS - The AIRC Institute of Molecular Oncology
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 700
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-01
Completion Date: 2028-09-01

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 B/C 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.

Primary Outcome Measures: 2-Year Recurrence-Free Survival (RFS), 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, radiological, or clinical findings., Assessed at 2 years post-surgery
Secondary Outcome Measures: 3-Year Recurrence-Free Survival (RFS), 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, radiological, or clinical findings., Assessed at 3 years post-surgery|5-Year Overall Survival (OS), 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., Assessed at 5 years post-surgery|Treatment Safety and Tolerability, 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., Assessed throughout the treatment period, up to 6 months|Sensitivity and Specificity of Liquid Biopsy in Detecting Residual Disease, 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 confirmed by imaging and clinical findings. Specificity will be measured by the ability to correctly identify patients without residual disease, also expressed as a percentage of negative results confirmed. The study will also assess the correlation between liquid biopsy results and traditional methods to ensure consistency in detecting residual disease., Assessed at regular intervals post-surgery, up to 2 years|Assessment of Quality of Life Using FACT-C Questionnaire, 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 based on patient responses to various questions, with each question rated on a scale from 0 to 4, with higher scores indicating better quality of life., 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|Assessment of Quality of Life Using EQ-5D-5L Questionnaire, 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 indicating no problems and 5 indicating extreme problems. The index score ranges from 0 to 1, with higher scores indicating better quality of life. Additionally, the EQ-5D-5L includes a visual analog scale (VAS) ranging from 0 (worst health imaginable) to 100 (best health imaginable) to assess the patient's overall health., 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