Clinical trial NCT06840665: MR-guided Adaptive Radiotherapy Combined With PD-1 Antibody and CAPOX for Locally Advanced Rectal Cancer
Official title: A Prospective, Randomized, Phase II Trial of MR-guided Adaptive Radiotherapy Combined With PD-1 Antibody and CAPOX for Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Rectal Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2025-02-21
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Pathological complete response (pCR) rate
timeFrame: 1 month after the surgery
Secondary outcomes:
measure: Grade 3-4 adverse effects rate
timeFrame: From the date of randomization until 3 months after the completion neoadjuvant therapy
measure: Anal function
timeFrame: From the date of randomization until 36 months after the surgery
measure: Surgical complication
timeFrame: The surgical complications were assessed within 3 months after the surgery
measure: 3-year local recurrence free survival (LRFS) rate
timeFrame: From the date of randomization until the date of first documented pelvic failure, assessed up to 36 months
measure: 3-year disease free survival (DFS) rate
timeFrame: 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
measure: 3-year overall survival (OS) rate
timeFrame: From the date of randomization until the date of death from any cause, assessed up to 36 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
References: