Study of High-Precision Evaluation of Molecular ResiduaL Disease Through a PlatfOrm for Cancer TracKing and Interception (SHERLOCK)

Advances in the detection and characterization of circulating tumor DNA (ctDNA) have enabled the introduction of "liquid biopsies" into clinical practice. Results from ctDNA testing of patients with certain advanced tumors (e.g., non-small cell lung cancer) are routinely used to inform decisions about drug treatment. With technological advances that improve the sensitivity of detection of ctDNA, a logical application is to apply ctDNA testing to potentially curable malignancies in patients who are at high risk of harboring minimal/molecular residual disease (MRD).

SHERLOCK is a platform study for the analysis of MRD using ctDNA in patients treated with curative intent for cancer. Exploratory and correlative analyses will also be conducted in order to investigate improved methods for MRD detection and interpretation. Clinical annotation will be performed to collect relevant patient and disease characteristics, treatment and outcomes.

Patients who are determined to be MRD positive may proceed to participate in interception clinical trials that are outside of this study's specified investigations. While on treatment, patients will continue to have blood and radiological imaging collected to measure for clearance of MRD and to correlate with outcomes.

Inclusion criteria

• Patients with histopathological confirmation of cancer. Patients whose diagnosis are made by cytology may also be considered for this study. For tumor types that are typically diagnosed using unequivocal imaging findings or biomarker profiles (e.g. hepatocellular cancer, uveal melanoma), they can be eligible without histopathological or cytological confirmation.
• Patients must have cancer that is planned for or has undergone curative intent treatment (e.g. surgery, definitive radiation, definitive chemoradiation, adjuvant radiation, adjuvant chemotherapy, adjuvant chemoradiation, etc). Curative intent treatment must be completed within 12 months of study entry. For patients on adjuvant/maintenance endocrine or biological therapy (e.g. bevacizumab, immunotherapy, etc), enrollment within 12 months of completion of curative intent treatment is allowed.
• Patient must be ≥ 18 years old.
• All patients must have signed and dated an informed consent form.

Exclusion criteria

• History of another active invasive cancer within 2 years prior to study enrolment. Exceptions include squamous and basal cell carcinoma of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, is considered cured with minimal risk of recurrence within 2 years.
• Prior allogeneic stem cell transplant