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 (May 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
Cancer type
Colorectal Cancer
Biomarker criteria
Excluded: MLH1 deficient mismatch repair
Known MSI-H or dMMR status
Excluded: MSH2 deficient mismatch repair
Known MSI-H or dMMR status
Excluded: MSH6 deficient mismatch repair
Known MSI-H or dMMR status
Excluded: PMS2 deficient mismatch repair
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)
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.
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