The study is a prospective, single-center, single-arm, two-cohort, phase II clinical trial. Patients aged 18 years or older who had pelvic recurrence rectal cancer with or without resectable distant metastasis, with treatment naive disease (cohort A) or progressive disease after first-line chemotherapy (cohort B), Eastern Cooperative Oncology Group performance status of 0-1, will receive 25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation (pelvic radiation history), 18 weeks toripalimab and investigator's choice of chemotherapy +/- target therapy, and stereotactic ablative radiotherapy (SABR) for all metastatic lesions between chemoimmunotherapy cycles, followed by multidisciplinary team (MDT) for decision:follow-up of complete response (CR), radical surgery, sustained treatment of non resection, or exit. The primary endpoint was local objective response rate. Secondary endpoints were extrapelvic objective response rate, R0 resection rate, duration of response, progression-free survival, overall survival, and safety and tolerability of the treatment. Shanghai Junshi Biomedical Technology Co., Ltd. Provides the first three cycles of toripalimab for free and has purchased liability insurance for clinical trial subjects.
For patients with locally recurrent rectal cancer (LRRC), response rate of chemoradiotherapy is 40-50% and only approximately 40-50% of patients with recurrent rectal cancer can undergo R0 resection. Recent studies have shown promising synergistic effects of the combination of immunotherapy (PD-1/PD-L1 antibodies) and neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). Thus, for LRRC patients, addition of immunotherapy to CRT is likely to further improve the response rate and prognosis.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
93
PD-1 antibody (Toripalimab): 240mg q3w or 160mg q2w
Capecitabine: 1000mg/m2 d1-14 q3w
400 mg/m2 (bolus) and 2400 mg/m2 (continuous infusion for 48hr)
400 mg/m2 q2w
130 mg/m² q3w or 85 mg/m² q2w
180 mg/m² q2w and 200 mg/m² q3w
2 mg/m² q2w and 3 mg/m² q3w
400 mg/m² q2w
5 mg/kg q2w or 7.5mg/kg q3w
25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation (pelvic radiation history) for pelvic recurrence tumor. 35-60Gy/5-8Fx irradiation for distance metastasis tumor.
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
RECRUITINGLocal objective response rate
the proportion of patients with the best pelvic response of confirmed complete or partial response according to RECIST 1.1, as assessed by the investigator.
Time frame: up to 1 year
Extrapelvic objective response rate
proportion of patients with confirmed extrapelvic complete or partial response per RECIST 1.1.
Time frame: up to 1 year
R0 resection rate
the proportion of patients who achieve R0 resection of pelvic recurrent tumour after therapy.
Time frame: up to 1 year
Duration of response (DOR)
time from the first documented pelvic objective response to pelvic or extrapelvic disease progression in patients with confirmed response.
Time frame: up to 1 year
Progression-Free Survival
time from the date of start treatment until disease progression or censored at last follow-up or death.
Time frame: up to 3 year
Overall Survival
from the date of start treatment until the date of death from any cause or censored at last follow-up.
Time frame: up to 3 year
Safety and tolerability of the treatment
proportion of patients with treatment-related acute toxicities as assessed by NCI CTCAE v5.0, from treatment initiation until 90 days upon completion of immunotherapy.
Time frame: up to 1 year
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