Locally Advanced Rectal Cancer, Neoadjuvant Therapy
Conditions
Brief summary
TORCH-iTNT is a prospective, multicentre, randomized phase II trial. 198 LARC (T3-4/N+M0, distance from anal verge ≤12cm) patients will be treated with total neoadjuvant therapy (TNT) and assigned to Group A and Group B (1:1). Group A receives 6 cycles of Toripalimab combined with CAPOX (ToriCAPOX). Group B receives SCRT (25Gy/5Fx) followed by 6 cycles of ToriCAPOX. TME surgery is scheduled after TNT while a watch and wait (W&W) option can be applied to patients achieving clinical complete response (cCR). The primary endpoint is complete response (CR, pathological complete response \[pCR\] plus cCR) rate. The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, organ or anal preservation rate, 3-year DFS rate, etc.
Interventions
DRUGPD-1 inhibitor
PD-1 inhibitor (Toripalimab): 240mg d1 q3w
DRUGCapecitabine
Capecitabine: 1000mg/m2 bid d1-14 q3w
RADIATIONShort-course radiotherapy
Short-course radiotherapy: 25Gy/5Fx
DRUGOxaliplatin
Oxaliplatin 130mg/m2 d1 q3w
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-70 years old, female and male; 2. Pathological confirmed adenocarcinoma; 3. The distance from anal verge ≤ 10 cm; 4. MSI/MMR status: MSS/pMMR; 5. Clinical stage T3-4 and/or N+, without distance metastases; 6. At least one of the following factors is present: distance from the anus ≤5 cm, cT4, cN2, positive cMRF, positive cEMVI, or positive lateral lymph nodes; 7. KPS ≥ 70; 8. No radiotherapy, chemotherapy, immunotherapy, or any other anti-tumor therapy had been administered prior to enrollment; 9. Baseline blood and biochemical indicators meet the following criteria: neutrophils ≥ 1.5 × 10\^9/L, Hb ≥ 90 g/L, PLT ≥ 100 × 10\^9/L, ALT/ AST ≤ 2.5 ULN, Cr ≤ 1 ULN; 10. With good compliance and signed the consent form.
Exclusion criteria
1. Pregnancy or breast-feeding women; 2. Known history of other malignancies within 5 years; 3. Known history of severe neurological or mental illness (such as schizophrenia, dementia or epilepsy); 4. Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction; 5. Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment; 6. Uncontrolled infection which needs systemic therapy; 7. Active autoimmune disease or immunodeficiencies, known history of organ transplantation or systematic use of immunosuppressive agents; 8. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection; 9. Allergic to any component of the therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete response (CR) rate | 1 month after the surgery or the decision of W&W | Rate of complete response (CR), including the rate of pathologic complete response (pCR) after surgery and the rate of cCR with W\&W strategy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Grade 3-4 adverse effects rate | From date of randomization until 3 months after the completion neoadjuvant therapy | Rate of chemotherapy, radiotherapy and immunotherapy related adverse events |
| 3 year organ or anal preservation rate | From date of randomization until the resection of rectum or anus, assessed up to 36 months. | 3 year organ or anal preservation rate |
| 3 year disease free survival rate | From 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 local recurrence free survival rate | From 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 distant metastasis free survival rate | From date of randomization until the date of first documented distant metastasis, assessed up to 36 months. | Rate of 3 year distant metastasis free survival |
| 3 year overall survival rate | From date of randomization until the date of death from any cause, assessed up to 36 months. | Rate of 3 year overall survival |
| Rate of surgical complications | The surgical complications were assessed within 3 months after the surgery. | Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc. |
Countries
China
Contacts
CONTACTZhen Zhang, MD
CONTACTYaqi Wang, MD
PRINCIPAL_INVESTIGATORZhen Zhang, MD
Fudan University
Outcome results
None listed