OncoMatch/Clinical Trials/NCT06958419
Node-Sparing Short-Course Radiotherapy Plus Chemotherapy, Bevacizumab and PD-1 Inhibitor in Metastatic pMMR/MSS Colorectal Cancer (MODIFI-CRC)
Is NCT06958419 recruiting? Yes, currently enrolling (Jun 2026). This Phase 2/3 trial studies multiple treatments including Node-Sparing Radiotherapy plus first-line therapy and First-line treatment for immune checkpoint therapy.
Treatment: Node-Sparing Radiotherapy plus first-line therapy · First-line treatment — The current standard first-line treatment for metastatic colorectal cancer is chemotherapy combined with targeted therapy, yet the prognosis remains poor. Although combining immunotherapy, anti-angiogenic agents, and chemotherapy has shown some efficacy in MSS/pMMR metastatic patients, progression-free survival (PFS) remains suboptimal. Radiotherapy-particularly high-dose radiotherapy-can enhance tumor antigen release and potentially improve the response of MSS/pMMR colorectal cancer to PD-1 inhibitors. Tumor-draining lymph nodes (TDLNs) are key sites for PD-1-mediated anti-tumor activity, but radiation-induced damage and fibrosis may impair their immune function. Prior studies have reported a remarkable pathologic complete response (pCR) rate of 77.8% using node-sparing radiotherapy in locally advanced rectal cancer. This phase II/III study aims to evaluate whether node-sparing modified short-course radiotherapy combined with chemotherapy, bevacizumab, and PD-1 blockade can improve objective response rate (ORR) in phase II and progression-free survival (PFS) in phase III, together with treatment tolerance, and overall prognosis in patients with pMMR/MSS metastatic colorectal cancer.
Check if I qualifyExtracted eligibility criteria
Treatments studied
Other
Cancer type
Colorectal Cancer
Biomarker criteria
Excluded: Mismatch-repair deficient (MSI-H / dMMR)
Known MSI-H or dMMR status
Disease stage
Required: Stage IV
Metastatic disease required
Patients must be considered unsuitable for curative surgical resection or local treatment and must not have received prior systemic anti-tumor therapy for recurrent or metastatic disease. At least one measurable lesion per RECIST v1.1
Performance status
ECOG 0–1(Restricted strenuous activity)
Demographics
Prior therapy
Cannot have received: immunotherapy
Prior immunotherapy, including immune checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies), immune agonists (e.g., ICOS, CD40, CD137, GITR, OX40), or immune cell-based therapies targeting tumor immunity.
Cannot have received: EGFR-targeted therapy (cetuximab, panitumumab)
Exception: adjuvant or neoadjuvant therapy allowed if recurrence/metastasis ≥12 months after last dose
Prior adjuvant or neoadjuvant therapy targeting EGFR or VEGF/VEGFR pathways (e.g., bevacizumab, cetuximab, panitumumab, aflibercept, regorafenib, or biosimilars).
Cannot have received: VEGF/VEGFR-targeted therapy (bevacizumab, aflibercept, regorafenib)
Exception: adjuvant or neoadjuvant therapy allowed if recurrence/metastasis ≥12 months after last dose
Prior adjuvant or neoadjuvant therapy targeting EGFR or VEGF/VEGFR pathways (e.g., bevacizumab, cetuximab, panitumumab, aflibercept, regorafenib, or biosimilars).
Cannot have received: systemic anti-tumor therapy
Exception: adjuvant or neoadjuvant therapy allowed if recurrence/metastasis ≥12 months after last dose
must not have received prior systemic anti-tumor therapy for recurrent or metastatic disease. Patients with prior neoadjuvant or adjuvant therapy may be enrolled if recurrence or metastasis occurs ≥12 months after the last dose of such treatment.
Cannot have received: systemic or local anti-tumor therapy for locally advanced rectal cancer
Prior systemic or local anti-tumor therapy for locally advanced rectal cancer, including curative surgery, chemotherapy, radiotherapy, immunotherapy, biologics, or small-molecule targeted therapy.
Lab requirements
Blood counts
ANC ≥ 1.5 × 10⁹/L; platelet count ≥ 100 × 10⁹/L; hemoglobin ≥ 90 g/L (no use of blood products or growth factors within 7 days prior to treatment)
Kidney function
Calculated creatinine clearance (CrCl) ≥ 50 mL/min; urine protein < 2+ on dipstick or < 1.0 g per 24-hour urine collection
Liver function
Total bilirubin ≤ 1.5 × ULN; AST and ALT ≤ 2.5 × ULN; serum albumin ≥ 28 g/L
Cardiac function
Left ventricular ejection fraction (LVEF) ≥ 50%
Adequate organ function as defined below: Hematologic...Renal...Hepatic...Coagulation...Cardiac...
Structured fields extracted by AI. May contain errors — verify against the official protocol.
Frequently asked questions
Is NCT06958419 currently recruiting?
Yes, this trial is currently recruiting patients.
Can patients have received prior systemic therapy?
No. This trial requires treatment-naive patients — prior systemic therapy is an exclusion criterion.
Are patients with MLH1 alterations eligible?
No. MLH1 deficient mismatch repair is an exclusion criterion.
Are patients with MSH2 alterations eligible?
No. MSH2 deficient mismatch repair is an exclusion criterion.
What disease stage is eligible?
Stage IV is required (metastatic disease required).
Is there an age limit?
Yes. Patients must be 75 years or younger.
Could you qualify for this trial?
Enter your biomarker results to see how this trial's eligibility criteria match your specific cancer profile.
Check if I qualifyRelated pages