This is an open-label, single arm, phase 2 study. The study is to evaluate the activity of combination therapy of hypofractionated radiotherapy, Irinotecan Hydrochloride Liposome plus 5-FU and leucovorin (NALIRIF), Anti-PD1 and target therapy in patients with locally recurrent rectal cancer (LRRC). The inclusion LRRC patients were failed to oxaliplatin treatment in prior chemotherapy or chemoradiotherapy due to toxicity or progression. Patients will receive 25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation for pelvic recurrence, 25-50Gy/5Fx irradiation for all metastasis sites, and 8 cycles of NALIRIF + anti-PD1 + target therapy, followed by multidisciplinary team (MDT) for decision: radical surgery, sustained system +/- local treatment of non resection. The primary endpoint was local objective response rate. Secondary endpoints were extrapelvic objective response rate, complete response rate, R0 resection rate, duration of response, progression-free survival, overall survival, and safety and tolerability of the treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
44
25-40Gy/5Fx or 15-30Gy/5Fx (previous pelvic radiation) for pelvic recurrence. 25-50GY/5Fx for all metastasis tumors. Dose Constraints are based on SABR-COMET 10 trial.
70mg/m2 (UGT1A1\*28 6/6) or 55mg/m2 (UGT1A1\*28 6/7), IV, q2w
400 mg/m\^2 bolus over 2 hours followed by 2400 mg/m\^2 continuous infusion over 48 hours d1, q2w
400mg/m2, IV, q2w
240mg, IV, q2w
500 mg/m2, IV, q2w
5mg/kg, IV, q2w
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
Complete response rate
proportion of patients with confirmed complete 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 3 year
Progression-Free Survival(PFS)
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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