MR-guided Adaptive Radiotherapy Combined With PD-1 Antibody and CAPOX for Locally Advanced Rectal Cancer

A Prospective, Randomized, Phase II Trial of MR-guided Adaptive Radiotherapy Combined With PD-1 Antibody and CAPOX for Locally Advanced Rectal Cancer

NeoPulsar is a prospective, randomized phase II trial. 46 LARC (T3-4/N+M0, distance from anal verge ≤12cm) patients will be treated with MR-guided adaptive radiotherapy (30Gy/6Fx) combined with 6 cycles of Toripalimab and CAPOX. TME surgery is scheduled after TNT. The primary endpoint is pathological complete response (pCR) rate. The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, anal function, surgical complication, 3-year LRFS rate, 3-year DFS rate, 3-year OS rate, etc.

Inclusion Criteria:

1. Age 18-70 years old, male or female
2. Pathologically confirmed rectal adenocarcinoma
3. The distance from anal verge ≤ 10 cm
4. Clinical stage T3-4 and/or N+
5. No evidence of distance metastases
6. MSI/MMR status: MSS/pMMR
7. Karnofsky score >=70
8. Adequate organ function and have no contraindications to surgery, radiochemotherapy, or immunotherapy
9. No chemotherapy or any other anti-tumor therapy prior to enrollment
10. No immunotherapy prior to enrollment
11. With good compliance during the study
12. Signed written informed consent

Exclusion Criteria:

1. Known history of other malignancies within 5 years， except cured skin cancer and cervical cancer in situ
2. Pregnancy or breast-feeding women
3. Individuals with a history of uncontrolled epilepsy, central nervous system disease, or psychiatric disorders that, in the judgment of the investigator, are of such clinical severity that they may prevent the signing of an informed consent form or affect the patient's adherence to oral medications
4. Individuals with clinically serious (i.e., active) heart disease, such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmia requiring pharmacologic intervention, or history of myocardial infarction within the last 12 months
5. Individuals with a history of organ transplantation requiring immunosuppressive therapy and long-term hormone therapy
6. Individuals with autoimmune diseases
7. Individuals with severe uncontrolled recurrent infections，or other severe uncontrolled concomitant diseases
8. Baseline hematology and biochemistry not meeting the following criteria: Hb≥90g/L; NEU ≥1.5×109/L; PLT ≥100×109/L; ALT, AST ≤2.5 times the upper limit of normal; ALP ≤2.5 times the upper limit of normal; TB <1.5 times the upper limit of normal; Cr <1 time the upper limit of normal; Alb ≥30g/L
9. Individuals with dihydropyrimidine dehydrogenase (DPD) deficiency
10. Individuals allergic to any drug component of the study