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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A | Experimental | 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 | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PD-1 antibody | Drug | PD-1 antibody (Toripalimab): 240mg d1 q3w |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pathological complete response (pCR) rate | Rate of pathologic complete response (pCR) after surgery | 1 month after the surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Grade 3-4 adverse effects rate | Rate of chemotherapy, radiotherapy and immunotherapy related adverse events | From the date of randomization until 3 months after the completion neoadjuvant therapy |
| Anal function |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Zhen Zhang, MD | Contact | +86 18017312217 | zhen_zhang@fudan.edu.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fudan University Shanghai Cancer Center | Recruiting | Shanghai | Shanghai Municipality | 200030 | China |
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| ID | Term |
|---|---|
| C000711728 | spartalizumab |
| C000656314 | toripalimab |
| D000077150 | Oxaliplatin |
| D000069287 | Capecitabine |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
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| Oxaliplatin | Drug | Oxaliplatin: 130mg/m2 d1 q3w |
|
| Capecitabine | Drug | Capecitabine: 1000mg/m2 bid d1-14 q3w |
|
Anal function will be evaluated using LARS score
| From the date of randomization until 36 months after the surgery |
| Surgical complication | Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc. | The surgical complications were assessed within 3 months after the surgery |
| 3-year local recurrence free survival (LRFS) rate | Rate of 3-year local recurrence free survival | From the date of randomization until the date of first documented pelvic failure, assessed up to 36 months |
| 3-year disease free survival (DFS) rate | Rate of 3-year disease free survival | 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 |
| 3-year overall survival (OS) rate | Rate of 3-year overall survival | From the date of randomization until the date of death from any cause, assessed up to 36 months |
| D011741 |
| Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |