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

Phase 2

Recruiting

• Conditions: Locally Advanced Rectal Cancer
• Interventions: Drug: PD-1 antibody; Drug: Oxaliplatin; Drug: Capecitabine

• Registration Number: NCT06840665
• Lead Sponsor: Fudan University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-08-13
• Status Verified: 2025-02
• Study First Submitted: 2025-02-15
• Study First Submitted QC: 2025-02-19
• Last Update Submitted: 2025-02-19
• Study First Posted: 2025-02-21
• Last Update Posted: 2025-02-21
• Primary Completion: 2026-08-12
• Study Completion: 2027-02-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 46

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A	PD-1 antibody	The patients will receive conventional pelvic radiotherapy (30Gy/6Fx), combined with 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT.
Group A	Oxaliplatin	The patients will receive conventional pelvic radiotherapy (30Gy/6Fx), combined with 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT.
Group A	Capecitabine	The patients will receive conventional pelvic radiotherapy (30Gy/6Fx), combined with 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT.
Group B	PD-1 antibody	The patients will receive lymph node-sparing radiotherapy (30Gy/6Fx), combined with 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT.
Group B	Oxaliplatin	The patients will receive lymph node-sparing radiotherapy (30Gy/6Fx), combined with 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT.
Group B	Capecitabine	The patients will receive lymph node-sparing radiotherapy (30Gy/6Fx), combined with 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT.

Primary Outcome Measures

Name	Time	Method
Pathological complete response (pCR) rate	1 month after the surgery	Rate of pathologic complete response (pCR) after surgery

Secondary Outcome Measures

Name	Time	Method
Grade 3-4 adverse effects rate	From the date of randomization until 3 months after the completion neoadjuvant therapy	Rate of chemotherapy, radiotherapy and immunotherapy related adverse events
Anal function	From the date of randomization until 36 months after the surgery	Anal function will be evaluated using LARS score
Surgical complication	The surgical complications were assessed within 3 months after the surgery	Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.
3-year local recurrence free survival (LRFS) rate	From the date of randomization until the date of first documented pelvic failure, assessed up to 36 months	Rate of 3-year local recurrence free survival
3-year disease free survival (DFS) rate	From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months	Rate of 3-year disease free survival
3-year overall survival (OS) rate	From the date of randomization until the date of death from any cause, assessed up to 36 months	Rate of 3-year overall survival

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China