UGT1A1-Based Irinotecan Therapy for Locally Advanced Rectal Cancer

This study is testing whether adjusting the dose of a chemotherapy drug called irinotecan based on a patient's genetic profile (specifically UGT1A1 gene variants) improves treatment for locally advanced rectal cancer. Certain gene variants affect how the body breaks down irinotecan, and tailoring the dose may improve effectiveness and reduce side effects. **You may be eligible if...** - You are between 18 and 75 years old with confirmed rectal adenocarcinoma (rectal cancer) - Your cancer is locally advanced (Stage T3-4 or lymph node involvement) and you are planned for chemoradiation treatment - Your cancer has not spread to distant organs - Your blood counts, liver, and kidney function are within acceptable limits - You have been genetically tested for relevant UGT1A1 variants **You may NOT be eligible if...** - You are pregnant or breastfeeding - You have had another cancer in the past 5 years (except treated skin cancer or cervical carcinoma in situ) - You have serious heart disease, a recent heart attack, or severe arrhythmia - You have had an organ transplant requiring immunosuppression - You have a DPD enzyme deficiency (which affects how fluorouracil-type drugs are broken down) - You are allergic to any of the study medications Talk to your doctor to see if this trial is right for you.