This is a phase II/III, multi-center, open-label, 3-arm, randomized controlled trial assessing the efficacy and safety of neoadjuvant long-course chemoradiation combined with Tislelizumab (PD-1 inhibitor) and subsequent TME surgery, by comparing assorted endpoints between two experiment groups (Experiment group 1: chemoradiation+concurrent PD-1 inhibitor; Experiment group 2: chemoradiation+sequential PD-1 inhibitor) with a control group (chemoradiation only).
This phase II, multi-center, open-label, 3-arm, randomized trial aims to recruit patients aged 18-75 years, diagnosed histologically as rectal adenocarcinoma, without metastasis (by CT), staged II/III (by MRI, T4b excluded), with distal margin within 10cm to anal verge. All patients should have no history of immune diseases, nor history of immunotherapy or radiotherapy. Sample size was thoroughly calculated to be 186. Eligible participants will be randomly assigned to Experiment Arm 1 (50.4Gy radiation, capecitabine, and anti-PD1 starting at Day 8 of radiation), Experiment Arm 2 (50.4Gy radiation, capecitabine, and anti-PD1 starting 2 weeks after completion of radiation), and Control Arm (50.4Gy radiation, capecitabine) in a 1:1:1 ratio. Randomization is stratified by different centers, with a block size of 6. For both experiment arms, Tislelizumab (anti-PD1) is scheduled to be administered at 200mg each time for 3 times, with 3-week intervals. The primary endpoint is pCR rate, and secondary endpoints include sphincter-preserving rate, adverse event rates, and DFS and OS rate at 2, 3 and 5 years post-operation. Data will be analyzed with an intention-to-treat or modified intention-to-treat approach.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
186
Tislelizumab is added to long-course chemoradiation (CRT) of LARC patients, with CRT+concurrent Tislelizumab for Arm 1, CRT+sequential Tislelizumab for Arm 2, and CRT only for Arm 3
Beijing Friendship Hospital, Capital Medical University
Beijing, Beijing Municipality, China
RECRUITINGBeijing Cancer Hospital
Beijing, Beijing Municipality, China
COMPLETEDBeijing Chaoyang Hospital, Capital Medical University
Beijing, Beijing Municipality, China
COMPLETEDBeijing Hospital
Beijing, Beijing Municipality, China
COMPLETEDPeking Union Medical College Hospital
Beijing, Beijing Municipality, China
RECRUITINGPeking University First Hospital
Beijing, Beijing Municipality, China
RECRUITINGPeking University People's Hospital
Beijing, Beijing Municipality, China
RECRUITINGXuanwu Hospital, Capital Medical University
Beijing, Beijing Municipality, China
COMPLETEDpCR rate
pathological complete response rate
Time frame: within 10 days after surgery
NAR score
neoadjuvant rectal score
Time frame: within 10 days after surgery
2-y OS rate
2-year overall survival rate
Time frame: 2 year
2-y DFS rate
2-year disease free survival rate
Time frame: 2 year
3-y OS rate
3-year overall survival rate
Time frame: 3 year
3-y DFS rate
3-year disease free survival rate
Time frame: 3 year
5-y OS rate
5-year overall survival rate
Time frame: 5 year
5-y DFS rate
5-year disease free survival rate
Time frame: 5 year
median OS time
median length (in months) of overall survival period
Time frame: 0~60 months
median DFS time
median length (in months) of disease free survival period
Time frame: 0~60 months
R0 resection rate
rate of R0 resection
Time frame: within 10 days after surgery
sphincter preserving rate
proportion of patients with preserved anal sphincter
Time frame: instantly after surgery
nearly pCR rate
nearly pathological complete response rate
Time frame: within 10 days after surgery
ORR
objective response rate
Time frame: before surgery
immune-related adverse event rate
adverse event rate that is deemed to be associated with PD-1 inhibition
Time frame: from commencing of PD-1 inhibition to the 30th day after surgery
Grade 3+ immune-related adverse event rate
adverse event (above Grade 3) rate that is deemed to be associated with PD-1 inhibition
Time frame: from commencing of PD-1 inhibition to the 30th day after surgery
treatment-related adverse event rate
adverse event rate that is deemed to be associated with all treatments
Time frame: from commencing of treatment to the 30th day after surgery
Grade 3+ treatment-related adverse event rate
adverse event (above Grade 3) rate that is deemed to be associated with all treatments
Time frame: from commencing of treatment to the 30th day after surgery
cCR rate
clinical complete response rate
Time frame: before surgery
incidence rate of surgical complications
incidence rate of surgical complications within 30 days after surgery
Time frame: within 30 days after surgery
incidence rate of Grade 3+ surgical complications
incidence rate of Grade 3+ surgical complications within 30 days after surgery
Time frame: within 30 days after surgery
quality of life score
quality of life score during the 5 years after surgery, multiple timepoint assessment
Time frame: during the 5 years after surgery
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