Table 3 Ongoing ctdna MRD-based prospective intervention trials in CRC
Trial Name (Clinical Trial No.) | Sample Size | Study Population | Analysis Method | Study Description | Primary Objective | |
|---|---|---|---|---|---|---|
CIRCULATE AIO-KRK-2017 (NCT04089631) | 4812 | Stage II | NGS | MRD-positive patients are randomized to: Surveillance vs. ACT (capecitabine or CAPOX) | 5-year DFS | |
CIRCULATE PRODIGE 70 (NCT04120701) | 1980 | Stage II | ddPCR | MRD-positive patients are randomized to: Surveillance vs. ACT (mFOLFOX6) | 3-year DFS | |
CIRCULATE-US (NCT05174169) | 1912 | Stage III | Signatera | MRD-positive: mFOLFOX6 3–6 months/CAPOX 3 months/no treatment MRD-negative: mFOLFOX6 6 month/CAPOX 6 month/mFOLFOX6 + 5-FU | 5-year DFS | |
BESPOKE (NCT04264702) | 1788 | Stage I-IV | Signatera | MRD-guided group: surveillance or ACT Standard of care group: traditional ACT | The impact of SIGNATERA™ on adjuvant treatment decisions | |
TRACC (NCT04050345) [99] | 1621 | High-risk Stage II and III | NGS | Standard of care group: CAPOX 3 months/Capecitabine 6 months MRD-guided group: MRD-positive, Traditional ACT; MRD-negative, chemotherapy de-escalated | 3-year DFS | |
NRG GI-005 /COBRA (NCT04068103) | 1408 | Low-risk Stage IIA | LUNAR-1 (Guardant Health) | Standard of care group: Surveillance MRD-guided group: MRD-positive, traditional ACT; MRD-negative, surveillance | 3-year DFS | |
MEDOCC-CrEATE (NL6281/NTR6455) | 1320 | Stage II | PGDx elio™ | Standard of care group: standard follow-up according to guideline MRD-guided group: MRD-positive, 8 cycles of capecitabine plus oxaliplatin; MRD-negative, standard follow-up according to guideline | the proportion of patients receiving ACT when ctDNA is detectable after resection | |
VEGA-CIRCULATE (UMIN000039205) | 1240 | High-risk stage II and low-risk stage III | Signatera | MRD-negative patients are randomized to: CAPOX 3 months vs. Surveillance/ALTAIR study | 2-year DFS | |
DYNAMIC-III (ACTRN-12617001566325) | 1000 | Stage III | Safe-SeqS | Standard of care group: traditional ACT MRD-guided group: MRD-positive, chemotherapy escalated; MRD-negative, chemotherapy de-escalated | 3-year RFS | |
CINTS-R (NCT05601505) | 465 | LARC | NGS | Standard of care group: traditional nCRT MRD-guided group: MSI-H/TMB-H or POLD/POLE2 mutation willed be arranged to receive immune therapy following nCRT; The others are arranged to randomly receive TNT or nCRT | 2 years of Disease-related treatment failure, DrTF | |
DYNAMIC (ACTRN-12615000381583) | 450 | Stage II | Safe-SeqS | Standard of care group: treated at the discretion of the clinicians MRD-guided group: MRD-positive, ACT; MRD-negative, surveillance | 3-year RFS | |
DYNAMIC-RECTAL (ACTRN-12617001560381) | 408 | LARC | Safe-SeqS | Standard of care group: treated at the discretion of the clinicians MRD-guided group: MRD-positive, ACT; MRD-negative, surveillance/ACT | whether an adjuvant therapy strategy based on ctDNA results in addition to standard pathologic risk assessment may affect the number of patients treated with chemotherapy | |
IMPROVE-IT2 (NCT04084249) | 254 | High-risk Stage II and Stage III | ddPCR, NGS | Standard of care group: standard follow-up according to guideline MRD-guided group: MRD testing every 4 months post-op for 24 months; PET-CT every 3 months if MRD turns positive | Fraction of patients with relapse receiving curative resection or local treatment | |
ALTAIR-CIRCULATE (NCT04457297) | 240 | Resectable Stage II-IV | Signatera | MRD-positive patients after 3 months of CAPOX are randomized to: trifluridine/tipiracil vs. surveillance | 3-year DFS | |
BNT122-01 (NCT04486378) | 201 | Resected Stage II (High Risk) and Stage III | Not reported | mRNA vaccine RO7198457 vs. standard treatment group MRD tested every 3 months | 5-year DFS | |
PEGASUS (NCT04259944) | 140 | Resected MSS stage III and high-risk stage II (T4N0) | LUNAR-1 (Guardant Health) | MRD-positive: CAPOX 3 months MRD-negative: capecitabine 6 months but will be retested after 1 cycle, and if MRD turns positive, will be switched to CAPOX. | Number of post-surgery and post-adjuvant false negative cases after a double MRD-negative detection | |
NCT05062317 | 120 | CRLM | Not reported | ctDNA (Low Risk): less intense chemotherapy ctDNA (High Risk): more intense chemotherapy | 1-year RFS | |
NCT05635630 | 110 | mCRC | Not reported | MRD-positive: adjuvant therapy; The ctDNA status is evaluated every 2 months. MRD-negative: Patients of MRD-negative group are monitored by ctDNA every 3 months. | 2-year RFS | |
NCT03436563 | 74 | Stage IV | Signatera | MRD-positive following resection of all metastases: M7824 (anti-PDL1/TGFbetaRII fusion protein) 6 doses | ORR and ctDNA clearance rate | |
IMPROVE-IT (NCT03748680) | 64 | Stage I and II | ddPCR, NGS | MRD-positive patients are randomized to: observation vs. FOLFOX/CAPOX 6 months. | 3-year DFS | |
CLAUDE (NCT05350501) | 34 | Stage II/III/IV | Not reported | MRD-positive patients after curative treatment: EO2040 (peptide vaccine) + Nivolumab | Number and percentage of patients with Treatment-Emergent Adverse Events | |