ctDNA methylation-guided adjuvant therapy after removing colorectal liver metastases

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a multicenter phase II randomized trial comparing ctDNA methylation-guided adjuvant therapy to conventional postoperative treatment in patients with resected colorectal cancer liver metastases. ctDNA methylation testing is performed about one week after surgery to decide on surveillance versus chemotherapy with or without targeted therapy, with decisions driven by ctDNA status and dynamics. In the ctDNA-guided arm, treatment is intensified if ctDNA is detectable and paused upon ctDNA clearance, up to a 6-month total duration and at most two restarts; ctDNA-negative patients enter regular surveillance. In the conventional arm, adjuvant therapy is chosen by investigators per standard practice. Stratification factors include RAS/BRAF status and primary tumor sidedness.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Age 18 to 75 years, regardless of sex.
* Histopathologically confirmed colorectal adenocarcinoma with liver metastases confirmed by contrast-enhanced CT or MRI.
* Liver metastases assessed as resectable by a multidisciplinary team, with R0 resection completed. Simultaneous or staged resection of the primary tumor and liver metastases is permitted. R0 resection is defined as negative surgical margins with no macroscopic or microscopic residual disease.
* No residual disease on contrast-enhanced CT or MRI performed within one month after surgery, confirming no evidence of disease (NED).
* No previous systemic anticancer treatment for metastatic disease, including chemotherapy, targeted therapy, or immunotherapy. If prior neoadjuvant or adjuvant chemotherapy was administered, the interval between the last dose and the diagnosis of liver metastases must be at least six months.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Postoperative peripheral blood samples (two 10-mL tubes) can be obtained for ctDNA methylation testing.
* Able to understand and voluntarily sign written informed consent.
* Willing and able to comply with the follow-up schedule specified in the study protocol.

Exclusion Criteria:

* Non-adenocarcinoma histology, such as neuroendocrine tumor, squamous cell carcinoma, or adenosquamous carcinoma.
* Extrahepatic metastases, including metastases to the lungs, bones, brain, peritoneum, or distant lymph nodes.
* Previous local treatment of the primary tumor or metastatic lesions, such as radiofrequency ablation or radiotherapy, without complete tumor eradication.
* Residual disease confirmed by imaging one month after surgery, indicating that NED has not been achieved.
* Microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) status and considered suitable for immunotherapy by the investigator.
* Severe hepatic or renal dysfunction (ALT/AST \>3 times the upper limit of normal \[ULN\], total bilirubin \>1.5 times ULN, or creatinine \>1.5 times ULN), or impaired bone marrow function (white blood cell count \<3.0 × 10\^9/L, neutrophil count \<1.5 × 10\^9/L, platelet count \<75 × 10\^9/L, or hemoglobin \<90 g/L).
* Uncontrolled severe hypertension (persistent systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg), severe infection, active hepatitis B (HBV DNA \>1000 copies/mL), hepatitis C (positive HCV RNA), or human immunodeficiency virus infection.
* History of serious cardiovascular or cerebrovascular disease, including New York Heart Association (NYHA) functional class III or higher, myocardial infarction or unstable angina within the past six months, or uncontrolled arrhythmia.
* Known allergy or contraindication to chemotherapy agents potentially used in the study (oxaliplatin, irinotecan, 5-fluorouracil, or capecitabine) or targeted agents (cetuximab beta or bevacizumab).
* Other malignancies, except non-melanoma skin cancer or cervical carcinoma in situ that has been treated curatively with no evidence of recurrence for more than five years.
* Pregnancy or breastfeeding, or refusal by participants of reproductive potential to use effective contraception during the study.
* History of alcohol abuse or drug abuse.
* Cognitive impairment or severe psychiatric illness that prevents understanding of or compliance with study requirements.
* Any other clinical or laboratory condition that, in the investigator's opinion, makes the participant unsuitable for this study.

Where it's running

• Fudan University Shanghai Cancer Center
  Shanghai, Shanghai Municipality, China Recruiting

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Using plasma ctDNA methylation to guide adjuvant chemotherapy for high-risk T3N0 colorectal cancer

  This will test whether a blood ctDNA methylation test can help choose stronger chemotherapy after surgery for people with high-risk T3N0 (stage II) colorectal cancer who are ctDNA-positive one month after surgery.

  Recruiting Phase 2 Fudan University · Shanghai · NCT07562711

• Plasma ctDNA methylation-guided adjuvant chemotherapy for stage I / low-risk stage II colorectal cancer

  This trial will test whether using a blood test for ctDNA methylation one month after surgery to guide adjuvant chemotherapy (such as capecitabine) helps clear ctDNA and lower recurrence risk in adults with stage I or low-risk stage II colorectal cancer who are ctDNA-positive.

  Recruiting Phase 2 Fudan University · Shanghai · NCT07562659

• Plasma ctDNA methylation-guided adjuvant chemotherapy for people with T4N0 and low‑risk stage III colorectal cancer.

  This trial will test whether using a blood test (plasma ctDNA methylation) to guide 3 vs 6 months of adjuvant chemotherapy or to switch regimens helps people with T4N0 or low‑risk stage III colorectal cancer after surgery.

  Recruiting Phase 2 Fudan University · Shanghai · NCT07562503

• Plasma ctDNA methylation–guided adjuvant chemotherapy for high-risk stage III colorectal cancer

  This trial will test whether adding bevacizumab to standard FOLFOX or CAPOX chemotherapy based on plasma ctDNA results helps adults with high-risk stage III colorectal cancer (T4N+ or T1-3N2).

  Recruiting Phase 2 Fudan University · Shanghai · NCT07562490

• AK104 plus radiotherapy with standard first-line treatment for pMMR/MSS colorectal cancer liver metastases

  This trial will test whether adding AK104 and targeted liver radiotherapy to standard first-line therapy helps people with pMMR/MSS colorectal cancer that has spread to the liver.

  Recruiting Phase 2 Fudan University · Shanghai · NCT07544784

• AI-based prediction of liver metastasis after colorectal cancer surgery

  This project will try a deep learning model that combines CT scans, digitized pathology slides, and routine clinical data to predict which stage I–III colorectal cancer patients are likely to develop liver metastases after curative surgery.

  Recruiting Tongji Hospital · Wuhan, Hubei · NCT07399236

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.