ctDNA-Guided Immunotherapy for dMMR/MSI-H Colon Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorFudan University
About this trial
This prospective, multicenter, single-arm phase II interventional study evaluates whether longitudinal circulating tumor DNA (ctDNA) monitoring can guide neoadjuvant immunotherapy and surgical decision-making in dMMR/MSI-H colon cancer. Participants with ctDNA clearance proceed to curative surgery, whereas those with persistent ctDNA positivity escalate to combined PD-1 and CTLA-4 inhibitor therapy.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Written informed consent obtained before any study-related procedures.
Age 18 to 75 years, inclusive.
Histologically confirmed colon adenocarcinoma, mucinous adenocarcinoma, or signet-ring cell carcinoma, with the tumor located at least 15 cm from the anal verge.
dMMR/MSI-H status confirmed by immunohistochemistry, polymerase chain reaction, or next-generation sequencing.
Disqualifiers
Prior treatment with a PD-1 inhibitor, CTLA-4 inhibitor, or other immunotherapy.
Symptomatic or high-risk bowel obstruction, bleeding, perforation, pneumonitis, or other conditions that may compromise safe study participation.
Another malignancy diagnosed within 5 years before the first study treatment, except for specified definitively treated low-risk malignancies.
Current participation in another interventional clinical study, or receipt of another investigational drug or investigational device within 4 weeks before the first study treatment.
Trial design
Design model
Single group
Treatments tested in this trial
PD-1 inhibitor
Drug200 mg intravenously on Day 1 of each 3-week cycle. All participants receive initial monotherapy.
CTLA-4 inhibitor
Drug1 mg/kg intravenously on Day 1 of each 3-week cycle. Administered with the PD-1 inhibitor only to participants with persistent ctDNA positivity after 3-4 cycles of monotherapy.
ctDNA/MRD testing
Diagnostic testPeripheral-blood ctDNA testing at baseline and after 3-4 cycles of monotherapy; every 2 cycles during combination therapy, when applicable; and 1 month after surgery.
Curative Surgery
Procedure/SurgeryCurative surgery after ctDNA clearance or after no more than 4 cycles of combination treatment.
Treatment groups
23 Participants
are divided into 1 treatment groupGroup A: ctDNA-Guided Neoadjuvant Immunotherapy |Experimental treatment 4 interventions
Trial outcomes
Primary outcomes
1
Pathological Complete Response Rate
Pathological assessment of the surgical resection specimen; pCR is defined as no residual viable cancer cells after treatment (ypT0N0M0).
Time frame
At curative surgery, following completion of neoadjuvant therapySecondary outcomes
1
Major Pathological Response Rate
Pathological assessment of the surgical resection specimen; MPR is defined as residual viable tumor cells ≤10%.
Time frame
At curative surgery, following completion of neoadjuvant therapy2
3-Year Event-Free Survival
Time from enrollment to first radiographic disease progression or death, whichever occurs first.
Time frame
From enrollment up to 3 years3
3-Year Overall Survival
Time from enrollment to death from any cause.
Time frame
From enrollment up to 3 years4
Concordance of ctDNA Status With Pathological Complete Response
Preoperative ctDNA status will be compared with postoperative pathological complete response results.
Time frame
After 3-4 cycles of PD-1 inhibitor monotherapy (21-day cycles) and at curative surgery; for persistent ctDNA positivity, every 2 cycles of PD-1 plus CTLA-4 inhibitor therapy (21-day cycles; up to 4 cycles).Sponsors and contacts
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Source ClinicalTrials.gov