Blood Test to Aid in Decisions Regarding Preventive Treatment for Stage II Colorectal Cancer

Colon cancer and rectal cancer (collectively referred to as colorectal carcinoma) are malignant diseases caused by the uncontrolled proliferation of cells in the intestinal mucosa. In UICC Stage II, the cancer cells have already infiltrated deeper layers of the intestinal wall (down to the so-called subserosa), but the surrounding lymph nodes are still cancer-free and there are no metastases (distant spread of cancer cells to other organs). The primary goal of treatment is complete removal of the tumor. Following successful surgery for stage II colorectal cancer, adjuvant therapy with chemotherapy—such as capecitabine (possibly in combination with oxaliplatin)—may also be recommended to reduce the risk of recurrence. Although studies have shown some benefit of chemotherapy at this stage of cancer, the results do not yet support a recommendation for its routine use. The goal of this Phase 3 study is to investigate the potential benefit of chemotherapy following surgery. Before the actual treatment decision is made, a blood test is performed as part of the study to determine whether circulating tumor DNA (ctDNA) is still detectable after surgery. In addition, the tumor tissue will be tested for microsatellite instability (MSI) or mismatch repair (MMR) defects. These tests will be performed during the hospital stay or up to five weeks after discharge. Neither the treating physicians nor the patients will be informed of the blood test results. Depending on the results of the blood test for circulating tumor DNA and the molecular analysis of the tumor tissue, patients will be assigned to different treatment arms within the study. If tumor DNA is detected in the blood after surgery (ctDNA-positive) and there is no microsatellite instability or mismatch repair defect, patients are randomly assigned in a 2:1 ratio. In this process, some patients in Group 1 will receive chemotherapy with capecitabine, possibly in combination with oxaliplatin—depending on the treating physicians’ assessment. The other patients (Group 2) will not receive any further treatment but will be closely monitored. For patients in whom no tumor DNA is detectable in the blood (ctDNA-negative), randomization also takes place, but at a 1:4 ratio. Group 1 (control arm 3) continues to participate in the study and undergoes regular follow-up examinations. Group 2 (control arm 4) is withdrawn from the study and receives follow-up care in accordance with standard medical practice. This means that—depending on the physician’s assessment—patients in control arm 4 will also receive chemotherapy with capecitabine (and oxaliplatin, if applicable). The study is blinded, meaning that medical staff, patients, study investigators, and those analyzing the results do not know who is receiving or has received which treatment. The treatments and follow-up examinations as part of the study will take place over a period of up to 5 years, during which the effectiveness of the therapy and the occurrence of recurrences, metastases, and possible patient deaths will be investigated. The primary endpoint of the study is disease-free survival. Women and men aged 18 and older with UICC Stage II colon cancer or rectal cancer are eligible to participate in this study. The treatment recommendation for rectal cancer must correspond to that for colon cancer.