Locally Advanced Rectal Cancer
Conditions
Brief summary
TORCH is a prospective, multicentre, randomized phase II trial. 130 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. Group A receives SCRT (25Gy/5Fx) followed by 6 cycles of Toripalimab combined with CAPOX (ToriCAPOX). Group B receives 2 cycles of ToriCAPOX followed by SCRT and 4 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, 3-year DFS rate, etc.
Interventions
DRUGPD-1 antibody
PD-1 antibody (Toripalimab): 240mg d1 q3w
DRUGCapecitabine
Capecitabine: 1000mg/m2 bid d1-14 q3w
DRUGOxaliplatin
Oxaliplatin: 130mg/m2 d1 q3w
RADIATIONShort-course radiotherapy
Shor-course radiotherapy: 25Gy/5Fx
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. Pathological confrmed adenocarcinoma 2. Clinical stage T3-4 and/or N+ 3. The distance from anal verge ≤12 cm 4. Without distance metastases 5. Age 18-70 years old, female and male 6. KPS \> =70 7. 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 8. 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 previous anti-tumor treatment, including radiotherapy, chemotherapy, immune checkpoint inhibitors, T cell-related therapy, etc 4. Known history of severe neurological or mental illness (such as schizophrenia, dementia or epilepsy) 5. Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction 6. Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment 7. Uncontrolled infection which needs systemic therapy 8. Active autoimmune disease or immunodefciencies, known history of organ transplantation or systematic use of immunosuppressive agents 9. Known history of human immunodefciency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection 10. Active Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (i.e., HBsAg positive or HBV DNA positive, HCV RNA positive if anti-HCV antibody testing positive) 11. Allergic to any component of the therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete response (CR) rate | The status of cCR will be evaluated after the completion of neoadjuvant therapy. The pCR rate will be evaluated after surgery. The cCR patients who adopted W&W strategy will be included into the CR rate caluculation. | 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 |
|---|---|---|
| 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 |
| Grade 3-4 adverse effects rate | From date of randomization until the date of death from any cause, assessed up to 5 years | Rate of chemotherapy, radiotherapy and immunotherapy related adverse events |
| Rate of Surgical complications | The surgery was scheduled 2-4 weeks after the end of neoadjuvant therapy. And the surgical complications were assessed up to 5 years from the surgery. | Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc. |
| Scores of Quality of Life | From date of randomization until the date of death from any cause, assessed up to 10 years | Quality of life will be evaluated using EORTC QLQ-C30, EORTC QLQ-CR29, LARS score and Wexner score. |
| 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 |
Countries
China
Outcome results
None listed