. 2021 Mar 28;26(8):651–659. doi: 10.1002/onco.13738

Table 4.

Genomic testing for MRD: relevant clinical trials

Clinical Trial	Relevant results
BESPOKE [38] NCT04264702	Prospective observational study enrolling patients with successfully resected stage II or stage III CRC who have FFPE tissues and whole blood samples available for analysis. Patients in this registry trial will receive tumor‐informed ctDNA testing (Signatera) and will be recommended for adjuvant treatment or observation by their treating physician. A control arm will consist of cases with stage II or III CRC with at least 2 years of follow‐up data. The primary endpoint will be to assess the impact of tumor‐informed ctDNA testing on adjuvant treatment decisions and the rate of recurrence among patients diagnosed with CRC who remain asymptomatic Additional secondary endpoints will assess clinical correlates of ctDNA testing, including clearance of MRD, percentage of patients undergoing surgery for oligometastatic recurrence, and QoL measures. Target enrollment is 1,000 patients.
COBRA [39] NRG GI005 NCT04068103	Phase II/III trial that aims to evaluate the predictive benefit of tumor‐uninformed ctDNA testing (LUNAR‐1 assay) for patients with stage IIA colon cancer following surgery, given that adjuvant therapy is generally not recommended for these patients. Primary objective (Phase II portion) is the rate of ctDNA clearance for patients treated with or without adjuvant chemotherapy following surgical resection, and for the Phase III portion, the rate of RFS for patients with ctDNA‐positive status treated with or without adjuvant chemotherapy following surgical resection of their stage IIA disease. Secondary objectives (e.g., prevalence of detectable ctDNA in stage IIA CRC following resection) and exploratory objectives are also planned, including, notably, association of quantitative ctDNA levels with time to event outcomes (e.g., RFS and OS) and cost‐effectiveness of ctDNA monitoring versus standard of care. Patients will be randomly assigned to close observation or prospective ctDNA assessment; for those deemed high risk by ctDNA assessment (i.e., positive ctDNA or MRD+), patients will be assigned to 6 months of adjuvant chemotherapy, whereas those who are negative for ctDNA (MRD−) will remain on active surveillance. Blood will be prospectively collected from the standard of care arm to be analyzed at a later time for ctDNA status to enable comparison of ctDNA clearance with chemotherapy. Approximately 1,400 patients are expected to be enrolled.

Clinical Trial

Relevant results

BESPOKE [38] NCT04264702

Prospective observational study enrolling patients with successfully resected stage II or stage III CRC who have FFPE tissues and whole blood samples available for analysis.
Patients in this registry trial will receive tumor‐informed ctDNA testing (Signatera) and will be recommended for adjuvant treatment or observation by their treating physician.
A control arm will consist of cases with stage II or III CRC with at least 2 years of follow‐up data.
The primary endpoint will be to assess the impact of tumor‐informed ctDNA testing on adjuvant treatment decisions and the rate of recurrence among patients diagnosed with CRC who remain asymptomatic
Additional secondary endpoints will assess clinical correlates of ctDNA testing, including clearance of MRD, percentage of patients undergoing surgery for oligometastatic recurrence, and QoL measures.
Target enrollment is 1,000 patients.

COBRA [39]

NRG GI005 NCT04068103

Phase II/III trial that aims to evaluate the predictive benefit of tumor‐uninformed ctDNA testing (LUNAR‐1 assay) for patients with stage IIA colon cancer following surgery, given that adjuvant therapy is generally not recommended for these patients.
Primary objective (Phase II portion) is the rate of ctDNA clearance for patients treated with or without adjuvant chemotherapy following surgical resection, and for the Phase III portion, the rate of RFS for patients with ctDNA‐positive status treated with or without adjuvant chemotherapy following surgical resection of their stage IIA disease.
Secondary objectives (e.g., prevalence of detectable ctDNA in stage IIA CRC following resection) and exploratory objectives are also planned, including, notably, association of quantitative ctDNA levels with time to event outcomes (e.g., RFS and OS) and cost‐effectiveness of ctDNA monitoring versus standard of care.
Patients will be randomly assigned to close observation or prospective ctDNA assessment; for those deemed high risk by ctDNA assessment (i.e., positive ctDNA or MRD+), patients will be assigned to 6 months of adjuvant chemotherapy, whereas those who are negative for ctDNA (MRD−) will remain on active surveillance.
Blood will be prospectively collected from the standard of care arm to be analyzed at a later time for ctDNA status to enable comparison of ctDNA clearance with chemotherapy.
Approximately 1,400 patients are expected to be enrolled.

Abbreviations: CRC, colorectal cancer; ctDNA, circulating tumor DNA; FFPE, formalin‐fixed, paraffin‐embedded; MRD, molecular/minimal residual disease; OS, overall survival; QoL, quality of life; RFS, recurrence‐free survival.