Locally Advanced Rectal Cancer
Conditions
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.
Interventions
DRUGPD-1 antibody
PD-1 antibody (Toripalimab): 240mg d1 q3w
DRUGOxaliplatin
Oxaliplatin: 130mg/m2 d1 q3w
DRUGCapecitabine
Capecitabine: 1000mg/m2 bid d1-14 q3w
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
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response (pCR) rate | 1 month after the surgery | Rate of pathologic complete response (pCR) after surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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 |
| 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 |
Countries
China
Contacts
Primary ContactZhen Zhang, MD
Outcome results
None listed