Periodic Reporting for period 1 - Sagittarius (A PRECISION MEDICINE TRIAL LEVERAGING BLOOD-BASED TUMOR GENOMICS TO OPTIMIZE TREATMENT IN OPERABLE STAGE III AND HIGH-RISK STAGE II COLON CANCER PATIENTS - THE SAGITTARIUS TRIAL)
Reporting period: 2023-07-01 to 2024-12-31
Approximately half of all patients diagnosed with locoregional stage II high-risk/stage III colon cancer (LRCC) relapse within two years from the time of curative surgery because of imaging-undetectable micro-metastatic residual disease (MMRD). Given the lack of reliable predictors of individual risk, LRCC patients are treated with one-fits-all adjuvant chemotherapy. This gunshot approach results in either over- or under-treatment. SAGITTARIUS aims to optimize the clinical management of LRCC patients by leveraging circulating tumor DNA (ctDNA) measurement in the patient’s bloodstream to diagnose MMRD and genomic landscape characterization of the patient’s tumors to personalize treatments. SAGITTARIUS is a pragmatic trial whereby real-world patients are treated in two parallel trials based on their MMRD status and the genomic landscape of their tumors. ctDNA-positive patients are randomized to conventional or personalized targeted therapy. ctDNA-negative patients are randomized to either a physician-choice path or Wait&See strategy. Sagittarius will allow for treatment to be better matched against the tumor biology, also allowing for better monitoring – via ctDNA – to assess disease evolution in each patient, minimizing harm and maximizing the odds of cure. The efficacy and effectiveness of this potentially ground-breaking new strategy of care will be measured via multiple outcomes, including safety and time-to-event variables, patient-reported outcome measures, and health-economics evaluation.
In the reporting period, we submitted the Sagittarius clinical study protocol to competent regulatory and ethical authorities via the Clinical Trials Information System (CTIS) and achieved clinical study approval in all the three EU countries where the Sagittarius approach is being tested: approval in Italy and Spain was obtained at month 11 and in Germany at month 17. We defined the questionnaires to be used in the SAGITTARIUS clinical study for Quality-of-Life data collection engaging colorectal cancer patients, and the Cost-Effectiveness Analysis protocol by collaborating with the hospital administrators in Italy and Spain.
We activated the first clinical site by month 15, while the first SAGITTARIUS patient was enrolled at month 16. As of December 2024 (month 18), eleven out of the twenty-six sites of the Sagittarius clinical network have been opened and actively recruiting patients, with the remaining centres set to open by March 2025 (month 21).
We activated the first clinical site by month 15, while the first SAGITTARIUS patient was enrolled at month 16. As of December 2024 (month 18), eleven out of the twenty-six sites of the Sagittarius clinical network have been opened and actively recruiting patients, with the remaining centres set to open by March 2025 (month 21).
The ongoing clinical research will ensure the future uptake of the Sagittarius approach.