Efficacy and Safety of Neoadjuvant Long-course Chemoradiation Plus Tislelizumab in Mid-low Locally Advanced Rectal Cancer: a Phase II, Multi-center, Open-label, Randomized Controlled Trial (POLARSTAR Trial)
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).
• aged 18\
⁃ 75
• ECOG score 0\
⁃ 2
• biopsy diagnosed rectal adenocarcinoma, distal margin within 10cm to anal verge
• no distant metastasis, staged II/III (T4b excluded) by MRI
• maximum diameter of rectal cancer lesion≥10mm according to baseline CT or MRI (i.e. a measurable lesion as per RECIST 1.1 criteria)
• willing and able to comply with study protocol
• consent to the use of blood and tissue specimens for study
• no history of previous anti-tumor treatment (e.g. radiation, chemo, immuno, bio, herbal, etc.)
• no disorders/diseases of immune system (e.g. systemic lupus erythematosus, rheumatoid arthritis, systemic vasculitis, scleroderma, pemphigus, dermatomyositis, mixed connective tissue disease, autoimmune hemolytic anemia, hyperthyroidism/hypothyroidism, ulcerative colitis, autoimmune hemolytic anemia, HIV infection, etc.)
• no significant dysfunction of major viscera (e.g. heart, lung, liver, kidney, etc.)
• no jaundice or gastrointestinal obstruction
• no acute/ongoing infection
• no significant irregularities in blood routine test and biochemical test results, particular requirements include: neutrophils≥1.5×109/L, HGB≥80g/L, platelet≥100×109/L, serum creatinine≤1.5×ULN, total bilirubin≤1.5×ULN, ALT、AST≤2.5×ULN
• no social or mental disorder
• for women of child-bearing age, a negative result of serological pregnancy test is required, and effective contraception measures from inclusion till 60 days after the last dose of study drug is required