Moderately Hypofractionated Radiotherapy, pMMR/MSS, Rectal Cancer, Serplulimab
Conditions
Brief summary
This study aims to observe and evaluate the efficacy and safety of moderately hypofractionated radiotherapy combined with chemotherapy and immunotherapy, compared with conventional neoadjuvant chemoradiotherapy, in patients with high-risk locally advanced colorectal cancer.
Interventions
CapOx Regimen Recommended Dose：Capecitabine: 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle.Oxaliplatin: 130 mg/m² intravenously on day 1 of each 21-day cycle. Serplulimab: 300 mg intravenously on day 1 of each 21-day cycle. Moderately Hypofractionated Radiotherapy：Delivered using a simultaneous integrated boost (SIB) technique.Gross tumor volume (GTV): 3.5 Gy per fraction; clinical target volume (CTV): 3.0 Gy per fraction.Once daily, 5 fractions per week, for a total of 10 fractions.Total dose: GTV 35 Gy, CTV 30 Gy.
DRUGSerplulimab
CapOx Regimen Recommended Dose：Capecitabine: 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle.Oxaliplatin: 130 mg/m² intravenously on day 1 of each 21-day cycle. Serplulimab: 300 mg intravenously on day 1 of each 21-day cycle. Long-course Concurrent Chemoradiotherapy：Delivered using a conventional fractionation schedule.Gross tumor volume (GTV): 1.8-2.0 Gy per fraction, total dose 50-50.4 Gy.Clinical target volume (CTV): 1.8 Gy per fraction, total dose 45 Gy.Once daily, 5 fractions per week.GTV receives 25-28 fractions; CTV receives 25 fractions.
OTHERCapOx+Long-course radiotherapy
CapOx Regimen Recommended Dose：Capecitabine: 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle.Oxaliplatin: 130 mg/m² intravenously on day 1 of each 21-day cycle. Long-course Concurrent Chemoradiotherapy：Delivered using a conventional fractionation schedule.Gross tumor volume (GTV): 1.8-2.0 Gy per fraction, total dose 50-50.4 Gy.Clinical target volume (CTV): 1.8 Gy per fraction, total dose 45 Gy.Once daily, 5 fractions per week.GTV receives 25-28 fractions; CTV receives 25 fractions.
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years and ≤ 75 years. * Histologically confirmed colorectal adenocarcinoma with the lower margin of the lesion ≤ 10 cm from the anal verge as assessed by MRI, and immunohistochemistry confirming pMMR, or genetic testing demonstrating MSI-L or MSS. * Presence of at least one of the following high-risk factors as assessed by pelvic MRI: cT4a/b; N2; extramural vascular invasion (EMVI+); mesorectal fascia involvement (MRF+); enlarged lateral lymph node (longest diameter \> 7 mm). * Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1 * No prior surgery, radiotherapy, chemotherapy, or targeted therapy. * Able to tolerate radiotherapy, chemotherapy, and immunotherapy: ECOG performance status score 0-2. Laboratory results: white blood cell count ≥ 4.0 × 10⁹/L, platelet count ≥ 100 × 10⁹/L, hemoglobin ≥ 80 g/L, ALT \< 2 × ULN, total bilirubin \< 35 μmol/L, serum creatinine \< 1.5 × ULN or creatinine clearance ≥ 50 mL/min, thyroid-stimulating hormone within normal range (patients with stable thyroid function after hormone replacement therapy may be enrolled). * Willing to participate and able to provide written informed consent.
Exclusion criteria
* Presence of distant metastasis. * Patients with stage I or II rectal cancer who do not require preoperative neoadjuvant therapy. * Severe diseases involving the heart, lung, brain, kidney, gastrointestinal tract, or other systemic conditions. * Untreated chronic hepatitis B or HBV carriers with HBV DNA \> 500 IU/mL, or patients positive for HCV RNA. Patients with inactive hepatitis B surface antigen (HBsAg) carriers, those with hepatitis B who have been treated and are stable (HBV DNA \< 500 IU/mL), and those who have been cured of hepatitis C may be enrolled. * Active autoimmune disease or history of autoimmune disease with potential for relapse. * Receipt of corticosteroids (at a dose equivalent to prednisone \> 10 mg/day) or other immunosuppressive therapy within 2 weeks prior to study drug administration. * History of thyroid dysfunction. * Severe chronic or active infection requiring systemic antifungal or antiviral therapy, including tuberculosis infection. * History of allergic constitution or allergy to multiple drugs. * History of prior pelvic radiotherapy. * History of inflammatory bowel disease. * Unwillingness to participate or inability to provide written informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Remission (CR) Rate | At the time of surgery for pCR, and at 1 year after achieving cCR for sustained cCR | Definition: The proportion of participants achieving complete remission, defined as: Pathologic complete response (pCR): No residual viable tumor cells detected in the resected specimen after neoadjuvant treatment (ypT0N0) Sustained clinical complete response (cCR): No evidence of residual tumor on digital rectal examination, endoscopy, and MRI, maintained for more than 1 year without surgery Assessment Method: Evaluated by investigators based on imaging, endoscopic findings, pathology (for surgical cases), and clinical examination |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 3-Year Disease-Free Survival (DFS) Rate | Up to 3 years after randomization | Time from randomization to evidence of disease recurrence within 3 years |
| 3-Year Overall Survival (OS) Rate | up to 5 years | Time from randomization to death from any cause. |
| 3-Year Event-Free Survival (EFS) Rate | up to 3 years from treatment | Defined as the time from the start of treatment to the occurrence of any of the following events, whichever occurs first: disease progression that precludes surgery, postoperative disease progression or recurrence (per RECIST v1.1), or death from any cause. |
| Objective Response Rate | Up to 1 years | The rate of participants that achieve either a complete response (CR) or a partial response (PR). |
| AE rate | 24months | Adverse event incidence rate |
Countries
China
Outcome results
None listed