The Sagittarius Trial

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.