Rectal Cancer
Conditions
Keywords
node-sparing radiation, PD-1, MSS, short-course radioation
Brief summary
This is a randomized, prospective, multicenter, open-label, Phase III clinical trial to evaluate node-sparing modified short-course radiation (Radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) combined with CAPOX and PD-1 Inhibitor (Tislelizumab) compared with standard short-course radiation combined with CAPOX for patients with MSS middle and low rectal cancer. A total of 170 patients will be enrolled in this trial. The primary endpoint is the rate of pathological complete response (pCR). The EFS rate, ORR, organ preservation rate, long-term prognosis, and adverse effects will also be analyzed.
Interventions
RADIATIONnode-sparing modified short-course radiotherapy
radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes: 25Gy/5Fx
DRUGPD-1 antibody
PD-1 antibody (Tislelizumab): 200mg d1 q3w
DRUGCapecitabine
Capecitabine: 1000mg/m2 d1-14 q3w
DRUGOxaliplatin
Oxaliplatin: 130mg/m2 d1 q3w
RADIATIONstandard short-course radiotherapy
radiation targeting the tumor bed and surrounding tumor-draining lymph nodes: 25Gy/5Fx
Sponsors
Sir Run Run Shaw Hospital
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. Patients who have a strong willingness to preserve the anus and are willing to receive neoadjuvant therapy. 2. Male or Female aged 18-75. 3. Patients diagnosed with low rectal cancer within 10 cm from the lower edge of the tumor to the anal verge by pelvic MRI and anorectoscopy, the clinical stage is cT3-4bN0/+M0, and the lymph nodes are limited to the mesorectum. 4. Histologically confirmed rectal adenocarcinoma; Genetic testing suggests MSI-L or MSS, or tumor biopsy immunohistochemistry reveals pMMR, that is, MSH1, MSH2, MSH6, and PMS2 are all positive. 5. Eastern Cooperative Oncology Group (ECOG) score 0-1. 6. No previous treatment (including anti-tumor therapy, immunotherapy or pelvic radiation). 7. Laboratory tests indicating no contraindications to radiotherapy, chemotherapy and immunotherapy. 8. Informed consent form signed.
Exclusion criteria
1. Patients with a previous history of malignant tumors besides rectal cancer. 2. Patients with distant metastases before enrollment. 3. Patients with positive internal or external iliac lymph nodes are assessed by MRI or CT. 4. Patients with obstruction, perforation, or bleeding that require emergency surgery. 5. Patients with severe concomitant diseases and estimated survival time ≤ 5 years. 6. Allergic to any component of the therapy. 7. Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of therapy. 8. Patients who have received any other experimental drug (including immunotherapy) or participated in another interventional clinical trial within 30 days before screening. 9. Factors leading to study termination, such as alcoholism, drug abuse, other serious illnesses (including psychiatric disorders) requiring combination therapy, and patients with severe laboratory abnormalities. 10. Patients with congenital or acquired immune deficiency (such as HIV infection). 11. Vulnerable groups, including mentally ill, cognitively impaired, critically ill patients, minors, pregnant or lactating women, illiterate, etc. 12. Other conditions that investigators consider not suitable for this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pathological complete response (pCR) rate | within 10 days after completion of surgery | Pathological complete response (pCR) rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| event free survival (EFS) | 3 years after randomization | the time from randomization until relapse or progression |
| overall response rate (ORR) | within 10 days after completion of chemotherapy | The ORR represents the proportion of patients whose tumor burden decreases by a pre-defined clinically meaningful threshold and is maintained for a minimum required duration, which included complete response (CR) rate and partial response (PR) rate |
| organ preservation rate | within 10 days after completion of chemotherapy | patients who are able to retain their rectum/anal sphincter after treatment, without requiring a permanent colostomy. |
| Disease free survival(DFS) | 3 years after chemotherapy or surgery | The three-year disease-free survival of patients. |
| Overall survival(OS） | 3 years after chemotherapy or surgery | The three-year overall survival of patients. |
| Adverse effects rate | From date of initiation of treatment until the date of death from any cause, assessed up to 5 years | Rate of radiotherapy, chemotherapy and immunotherapy related adverse events |
| Rectal specific quality of life assessment via QLQ-CR29 Rectal specific quality of life assessment via QLQ-CR29 Rectal specific quality of life assessment via QLQ-CR29 | Baseline and months 3, 6, 12, 24, 36, 60 after the chemotherapy or surgery | Rectal specific quality of life according to European Organization for Research and Treatment of Cancer ( EORTC) Quality of life questionnaire QLQ-CR29. scale from 0 to 100, A higher scale represents better function and a higher quality of life. |
| Quality of life assessment via QLQ-C30 | Baseline and months 3, 6, 12, 24, 36, 60 after the chemotherapy or surgery | Quality of life according to EORTC Quality of life Questionnaire QLQ-C30 version 3.0. Score range from 0 to 100 points. A higher score represents better function and a higher quality of life |
| Validation of the Wexner score | Baseline and months 3, 6, 12, 24, 36, 60 after the chemotherapy or surgery | The change of severity of fecal incontinence assessment according to Wexner score. a score from 0-20, where 0 is perfect continence and 20 is complete incontinence. |
Countries
China
Outcome results
None listed