Minimal Residual Disease Assessment in Colorectal Cancer (MiRDA-C) Trial: Surveillance with Circulating Tumor DNA
Introduction
Detection of circulating tumor DNA (ctDNA) as a marker for minimal residual disease (MRD) in colorectal cancer (CRC) patients (pts) is becoming increasingly available and common. Clinical trials have already shown that detection of ctDNA-defined MRD has very high specificity and positive predictive value (PPV) for future radiographic recurrence with a lead time of over nine months following curative intent treatments. Prospective clinical trials similarly using ctDNA-defined MRD are now being conducted to improve adjuvant chemotherapy. However, largescale prospective data regarding kinetics of ctDNA-defined MRD, with accurate preanalytical methodology for plasma isolation and paired clinical data, are limited, nor have they established the clinical utility of MRD monitoring, especially following curative intent treatments. This trial aims to address these gaps by 1) evaluating PPV, sensitivity, and specificity of serial MRD monitoring for radiographic recurrences, and 2) estimating disease free survival and overall survival in pts with ctDNA-defined MRD following curative intent treatments.
Methods
In this multi-center prospective observational trial, 1,000 pts with resectable CRC (stages II-IV), without other active malignancies, undergoing therapy with curative intent are being enrolled any time from time of diagnosis up to start of adjuvant therapy (or ≤ 3 months post curative surgery, whichever is earlier). All therapeutic and surveillance visits decisions are at the discretion of the treating physicians. Serial biospecimens, including blood processed to plasma and buffy coat in ≤ 2 days and formalin fixed tumor tissue, are being collected at key time points until the time of radiographic recurrence or up to five years of surveillance. Blood draws are at study entry, after each line of neoadjuvant therapy, post-surgery, during and after adjuvant therapy in addition to each surveillance visit and coordinated with pts’ standard of care blood draws to minimize additional venipunctures. Relevant clinical data, including demographics, cancer history, treatment details and outcomes, serum tumor markers, and genomic data are also collected at each time point. Samples will be retrospectively evaluated utilizing an MRD assay with a primary objective of evaluating PPV, sensitivity, and specificity of post-operative MRD for radiographic recurrences. Other key objectives include evaluating ctDNA kinetics with neoadjuvant and adjuvant therapies and correlating outcomes.
Results
Approximately 570 pts have been enrolled across five Texas sites since initial activation at the lead site in September 2021. Past enrollment was significantly impacted by COVID; however, recent monthly enrollment has increased by approximately 50%. Demographically, 60% of pts are male and 40% are female with a median age of 53 years and range of 25-84 years. The majority of pts have tumor location equally distributed between colon (45%) and rectum (45%), with the remaining having rectosigmoid junction (6%) and multiple locations (4%). Pts’ TNM staging are 8%, 19%, 35%, and 38% respectively for stages I-IV. Approximately 1,190 blood samples have been collected, each consisting of 24 mLs of plasma. The majority of blood samples were collected at neoadjuvant (26%) and surveillance (38%) visits.
Conclusion
MiRDA-C is a multi-center prospective observational trial evaluating the performance of an MRD assay to detect ctDNA in risk stratification of CRC pts. Key findings from the trial’s progress include the feasibility of conducting clinical trials in the CRC MRD space as evidenced by robust enrollment and sample collection. The trial is active and enrolling pts at five Texas sites.