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.
Patient is 18-75 years old at the time of signing the informed consent form.
ECOG performance status 0-1.
MRI/enhanced CT confirmed pelvic recurrence. According to RECIST 1.1, there is at least one measurable pelvic lesion.
Distant metastasis lesions are no more than 5 and metastatic organ are no more than 3.
Neutrophil < 1.5×10^9/L, PLT < 100×10^9/L (PLT < 80×10^9/L in patients with liver metastasis), or Hb < 90g/L; blood transfusion within 2 weeks before enrollment is not allowed to meet the enrollment criteria.
TBIL > 1.5 ULN, or TBIL > 2.5 ULN in patients with liver metastasis.
AST or ALT > 2.5 ULN, or ALT and / or AST > 5 ULN in patients with liver metastasis.
Cr > 1.5 ULN, or creatinine clearance < 50ml / min (calculated according to Cockcroft Gault formula).
Single group
PD-1 antibody
DrugPD-1 antibody (Toripalimab): 240mg q3w or 160mg q2w
Capecitabine
DrugCapecitabine: 1000mg/m2 d1-14 q3w
5FU
Drug400 mg/m2 (bolus) and 2400 mg/m2 (continuous infusion for 48hr)
folinic acid
Drug400 mg/m2 q2w
Oxaliplatin
Drug130 mg/m² q3w or 85 mg/m² q2w
Irinotecan
Drug180 mg/m² q2w and 200 mg/m² q3w
Raltitrexed
Drug2 mg/m² q2w and 3 mg/m² q3w
Cetuximab
Drug400 mg/m² q2w
Bevacizumab
Drug5 mg/kg q2w or 7.5mg/kg q3w
Radiation
Radiation25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation (pelvic radiation history) for pelvic recurrence tumor. 35-60Gy/5-8Fx irradiation for distance metastasis tumor.
Local 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.
Extrapelvic objective response rate
proportion of patients with confirmed extrapelvic complete or partial response per RECIST 1.1.
R0 resection rate
the proportion of patients who achieve R0 resection of pelvic recurrent tumour after therapy.
Duration of response (DOR)
time from the first documented pelvic objective response to pelvic or extrapelvic disease progression in patients with confirmed response.
Progression-Free Survival
time from the date of start treatment until disease progression or censored at last follow-up or death.
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