ORACLE: Observation of Residual Cancer Using Liquid Biopsy Evaluation

When cancer cells grow or die, they release small fragments of their genetic material into the bloodstream. These fragments are known as circulating tumor DNA (ctDNA). Using a procedure called a liquid biopsy—a minimally invasive blood test—the blood can be specifically screened for these tumor DNA fragments without the need for a tissue biopsy. The ORACLE study uses a specialized ctDNA test (Guardant Reveal) designed to detect even the smallest remaining traces of tumor or cancer cells in the body (minimal residual disease, MRD) after cancer treatment has been completed. The presence of ctDNA in the blood after treatment may indicate an increased risk of cancer recurrence.

The goal of this observational study is to investigate whether this blood test can reliably detect a relapse earlier than standard imaging procedures and clinical examinations. This is an observational study in which no new treatment is being tested. Patients’ regular follow-up care and treatment will remain unchanged. The only difference is that additional blood samples will be taken and tested for ctDNA. The results of the blood test will not influence further treatment. The study includes twelve different cohorts for various tumor types. These include, among others, muscle-invasive bladder cancer (including ureteral and renal pelvic cancer), non-small-cell lung cancer, breast cancer with various receptor characteristics (HER2-positive, triple-negative, or hormone receptor-positive/HER2-negative), cutaneous melanoma, esophageal and gastric cancer, pancreatic cancer, squamous cell carcinoma of the head and neck, ovarian and fallopian tube cancer, uterine cancer, renal cell carcinoma, and colorectal cancer. Blood samples will be collected over a period of up to three years. The main objective (primary endpoint) of the study is to evaluate the distant recurrence-free interval (D-RFi), that is, the time until the occurrence of a recurrence with distant metastases (spread of the cancer beyond the originally affected organ). In addition, the study will examine how reliable the test is and how far in advance it can indicate a recurrence (lead time). The study does not test a new drug and has no impact on the patients’ treatment.

Patients aged 18 and older who have been treated for early-stage cancer with the goal of a cure (curative treatment) are eligible to participate in the study. A prerequisite is that there are no known distant metastases at the time of enrollment and that patients are able to participate in regular follow-up examinations. In addition, they must be willing to provide regular blood samples over an extended period of time.