STUDY TITLE: PRECISION-MRD: Prospective Observational Study of Biomarker-Directed Systemic Therapy for Colorectal Cancer Patients with Minimal Residual Disease

CtDNA technology has allowed for the detection of patients with microscopic metastatic disease despite resection followed by standard of care adjuvant therapy. NCCN guidelines support the use of biomarker directed targeted therapies.  The goal of this clinical research study is to learn about the effects of biomarker-targeted therapy on ctDNA in participants with CRC and MRD.  This is an observational study. Participants will be monitored while receiving biomarker-directed therapy that is determined by the treating oncologist (cancer doctor) per standard-of-care, independent of this study.

Key Eligibility Criteria

1. Histologically or cytologically confirmed diagnosis of colorectal adenocarcinoma.
2. Stage II-IV disease with no definitive radiographic evidence of disease following locoregional treatment. Small indeterminate lesions measuring < 10 mm may be permitted at the discretion of the principal investigator.
3. Presence of one of the following targetable biomarkers on tumor or blood molecular testing:

  • BRAF V600E mutation (Cohort A),
  • KRAS G12C mutation (Cohort B),
  • MSI-H status (Cohort C),or
  • HER2 amplification (Cohort D).

4. Positive ctDNA blood test obtained > 21 days after surgery or last administration of adjuvant therapy.
5. Prescribed one of the following standard-of-care targeted therapy regimens:

  • BRAF V600E Inhibitor + anti-EGFR antibody for BRAF V600E-mutated tumors,
  • KRAS G12C Inhibitor + anti-EGFR antibody for KRAS G12C-mutated tumors,
  • anti-PD-1 antibody +/- anti-CTLA-4 antibody for MMRd/MSI-H tumors, or
  • anti-HER2 therapies for HER2 amplified tumors.

Exclusion Criteria

1. Prior exposure to the following classes of biomarker-directed therapies: BRAF V600E inhibitors, anti-EGFR antibodies, KRAS G12C inhibitors, anti-PD-1/PD-L1 antibodies, anti-CTLA-4 antibodies, or anti-HER2 therapies.
2. Presence of a concurrent malignancy requiring active treatment.

Visit and Treatment Details

This study will follow standard-of-care treatment, duration, and restaging schedule as determined by the treating oncologist (cancer doctor).  Participants that take part in this research, will be responsible for following study directions and allowing blood samples to be collected every 3 months for correlative studies.

Standard-of-care targeted therapy regimens as determined by the treating oncologist (cancer doctor):

  • BRAF V600E Inhibitor + anti-EGFR antibody for BRAF V600E-mutated tumors,
  • KRAS G12C Inhibitor + anti-EGFR antibody for KRAS G12C-mutated tumors,
  • anti-PD-1 antibody +/- anti-CTLA-4 antibody for MMRd/MSI-H tumors, or
  • anti-HER2 therapies for HER2 amplified tumors.
Click below link to ClinicalTrials.gov for more details:

Study Record