A Prospective Phase Ib/II Trial of Radiotherapy Combined With Tyrosine Kinase Inhibitor and Immune Checkpoint Inhibitor in High-Risk Localized Soft Tissue Sarcoma (IRIS)
This is a prospective, single-center, single-arm, phase Ib/II clinical trial. The study aims to evaluate the safety and efficacy of the treatment which combines radiotherapy, Sintilimab (Anti-PD1 Antibody) and Surufatinib (small-molecule Tyrosine Kinase inhibitor) in patients with high-risk localized soft tissue sarcoma. There will be 52 patients with high-risk localized extremity and trunck soft tissue sarcoma recruited. The trail is designed as a two-stage study. In safety lead-in phase (phase Ib), using 3+3 design, 6 cycles of Surufatinib (250mg, 200mg, qd) and Sintilimab (200mg, q3w) will be applied. And radiotherapy (BED=50-60Gy (α/β=10)) will begin in week 4 of the therapy. In extended phase (phase II), Surufatinib will be applied in the recommended phase 2 dose (RP2D) according to phase Ib. And 200mg Sintilimab and radiotherapy will be applied as before. The dose-limiting toxicity (DLT) in phase Ib and objective response rate (ORR) in phase Ib+Phase II will be mainly analyzed.
• Aged from 18 to 70, with life expectancy more than 2 years
• Histologically confirmed STS, G2 or G3
• Has imaging-confirmed localized lesions on the limbs or trunk without distant metastases
• Has\>5 cm lesions, or the lesions are determined to be borderline resectable or unresectable by a multidisciplinary consultation.
• Experience local recurrence after surgery (disease-free survival more than 2 months after surgery) or primary tumor
• ECOG performance status 0-1
• Demonstrate adequate organ function (bone marrow, liver, kidney and clotting function) within 7 days before the first administration without using blood products or hematopoietic stimulating factors.
• Fully informed and willing to provide written informed consent for the trial