OncoMatch/Clinical Trials/NCT06958432
Node-Sparing Short-Course Radiotherapy Sequential Chemotherapy and PD-1 Inhibitor for Mid/Low pMMR/MSS Rectal Cancer (MODIFI-RC-II)
Is NCT06958432 recruiting? Yes, currently enrolling (Jun 2026). This Phase 2/3 trial studies multiple treatments including Node-Sparing Radiotherapy plus Chemotherapy and PD-1 inhibitor and Conventional Radiotherapy plus Chemotherapy and PD-1 inhibitor for rectal cancer.
Treatment: Node-Sparing Radiotherapy plus Chemotherapy and PD-1 inhibitor · Conventional Radiotherapy plus Chemotherapy and PD-1 inhibitor — Most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) and respond poorly to PD-1 inhibitors. Radiotherapy can enhance tumor antigen release and improve responsiveness to PD-1 blockade in MSS/pMMR rectal cancer. Tumor-draining lymph nodes (TDLNs) are critical sites for anti-tumor immune activation, but radiation-induced damage and fibrosis may impair lymphatic drainage and immune responses. Previous studies have reported a remarkable pathologic complete response (pCR) rate of 77.8% using node-sparing radiotherapy in locally advanced rectal cancer. This study aims to evaluate whether node-sparing short-course radiotherapy followed by sequential chemotherapy and PD-1 blockade can improve complete response rate in the phase II part and event-free survival in phase III part, together with sphincter preservation, treatment tolerance, and prognosis in patients with mid-low pMMR/MSS rectal cancer.
Check if I qualifyExtracted eligibility criteria
Treatments studied
Other
Cancer type
Colorectal Cancer
Biomarker criteria
Required: MSH2 proficient mismatch repair (pMMR) (positive immunohistochemical staining)
proficient mismatch repair (pMMR), defined by positive immunohistochemical staining for MSH1, MSH2, MSH6, and PMS2
Required: MSH6 proficient mismatch repair (pMMR) (positive immunohistochemical staining)
proficient mismatch repair (pMMR), defined by positive immunohistochemical staining for MSH1, MSH2, MSH6, and PMS2
Required: PMS2 proficient mismatch repair (pMMR) (positive immunohistochemical staining)
proficient mismatch repair (pMMR), defined by positive immunohistochemical staining for MSH1, MSH2, MSH6, and PMS2
Required: MLH1 proficient mismatch repair (pMMR) (positive immunohistochemical staining)
proficient mismatch repair (pMMR), defined by positive immunohistochemical staining for MSH1, MSH2, MSH6, and PMS2
Disease stage
Required: Stage T3-4N0M0, TANYN+M0
Excluded: Stage T1N0, T2N0
Performance status
ECOG 0–1(Restricted strenuous activity)
Demographics
Prior therapy
Cannot have received: radiotherapy
No prior systemic or local anti-tumor treatment for rectal cancer, including radiotherapy, chemotherapy, immunotherapy, biologics, or small-molecule targeted therapy
Cannot have received: chemotherapy
No prior systemic or local anti-tumor treatment for rectal cancer, including radiotherapy, chemotherapy, immunotherapy, biologics, or small-molecule targeted therapy
Cannot have received: immunotherapy
No prior systemic or local anti-tumor treatment for rectal cancer, including radiotherapy, chemotherapy, immunotherapy, biologics, or small-molecule targeted therapy
Cannot have received: biologics
No prior systemic or local anti-tumor treatment for rectal cancer, including radiotherapy, chemotherapy, immunotherapy, biologics, or small-molecule targeted therapy
Cannot have received: small-molecule targeted therapy
No prior systemic or local anti-tumor treatment for rectal cancer, including radiotherapy, chemotherapy, immunotherapy, biologics, or small-molecule targeted therapy
Cannot have received: curative surgery
Prior systemic or local anti-tumor therapy for locally advanced rectal cancer, including curative surgery, chemotherapy, radiotherapy, immunotherapy (e.g., immune checkpoint inhibitors, agonists, or cell-based therapies), biologics, or small-molecule targeted therapy
Lab requirements
Blood counts
ANC ≥ 1.5 × 10⁹/L; Platelet count ≥ 100 × 10⁹/L; Hemoglobin ≥ 90 g/L
Kidney function
Calculated creatinine clearance (CrCl) ≥ 50 mL/min using Cockcroft-Gault formula; Urine protein < 2+ on dipstick or < 1.0 g per 24-hour 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, defined as follows: Hematologic (without use of blood components or growth factors within 7 days prior to treatment initiation): Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; Platelet count ≥ 100 × 10⁹/L; Hemoglobin ≥ 90 g/L; Renal: Calculated creatinine clearance (CrCl) ≥ 50 mL/min using the Cockcroft-Gault formula; Urine protein < 2+ on dipstick or < 1.0 g per 24-hour collection; Hepatic: Total bilirubin ≤ 1.5 × ULN; AST and ALT ≤ 2.5 × ULN; Serum albumin ≥ 28 g/L; Coagulation: INR and APTT ≤ 1.5 × ULN; Cardiac: Left ventricular ejection fraction (LVEF) ≥ 50%
Structured fields extracted by AI. May contain errors — verify against the official protocol.
Frequently asked questions
Is NCT06958432 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.
Does this trial require MSH2?
Yes, MSH2 proficient mismatch repair (pMMR) is a required biomarker for enrollment.
Does this trial require MSH6?
Yes, MSH6 proficient mismatch repair (pMMR) is a required biomarker for enrollment.
Does this trial require PMS2?
Yes, PMS2 proficient mismatch repair (pMMR) is a required biomarker for enrollment.
What disease stage is eligible?
Stage T3-4N0M0 or TANYN+M0 is 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 qualify