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)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •The presence of regional or distant metastases detected by imaging evaluation
- •The following histological types: osteosarcoma, chordoma, classic chondrosarcoma, Kaposi's sarcoma, malignant mesothelioma, radiation-induced sarcomas
- •History of another primary malignant tumor within the past three years or at the same time (excluding localized basal cell carcinoma, cutaneous squamous cell carcinoma, ductal carcinoma in situ, lobular carcinoma in situ, adenocarcinoma in situ of cervix, or other previous malignant tumor with a disease-free survival of more than 10 years)
- •Receiving any other chemotherapy or targeted therapy within 4 weeks before enrollment
- •Prior treatment using anti-PD1 immunotherapy
- •Prior radiotherapy towards the target lesion or has other contraindications to radiotherapy or surgery
- •Baseline laboratory indicators do not meet the following criteria: neutrophils
- •≥1.5×10^9/L, Hb≥90g/L, PLT≥100×10^9/L , ALT ≤2.5 ULN, AST ≤2.5 ULN, Cr≤ 1.5 ULN or creatinine clearance rate <50ml/min, TBIL ≤1.5 ULN, APTT≤1.5 ULN, PT ≤1.5 ULN
- •Urinary protein ≥ 2+, or 24-hour urine protein ≥1.0g/24h
- •Uncontrolled hypertension: SBP >140mmHg or DBP > 90mmHg
- •Uncontrolled hyperglycemia or coagulation disorder
- •Active infection requiring systemic anti-infective therapy
- •Uncontrolled mental diseases
- •Previous surgery within 2 weeks of before enrollment (excluding diagnostic biopsy or peripherally inserted central catheter implantation)
- •History of immunodeficiency diseases or active autoimmune disease requiring systemic treatment
- •Pregnant or lactating women
- •Allergic to any component of the therapy
研究组 & 干预措施
Treatment Arm
There will be 52 patients with high-risk localized extremity and truncal soft tissue sarcoma recruited.
In safety lead-in phase (phase Ib): using 3+3 design, patients will receive 6 cycles of Surufatinib in three different dosages and Sintilimab. And radiotherapy will begin in week 4.
In extended phase (phase II): Surufatinib in RP2D, Sintilimab and radiotherapy will be applied as before.
干预措施: Sintilimab (Drug)
Treatment Arm
There will be 52 patients with high-risk localized extremity and truncal soft tissue sarcoma recruited.
In safety lead-in phase (phase Ib): using 3+3 design, patients will receive 6 cycles of Surufatinib in three different dosages and Sintilimab. And radiotherapy will begin in week 4.
In extended phase (phase II): Surufatinib in RP2D, Sintilimab and radiotherapy will be applied as before.
干预措施: Surufatinib (Drug)
Treatment Arm
There will be 52 patients with high-risk localized extremity and truncal soft tissue sarcoma recruited.
In safety lead-in phase (phase Ib): using 3+3 design, patients will receive 6 cycles of Surufatinib in three different dosages and Sintilimab. And radiotherapy will begin in week 4.
In extended phase (phase II): Surufatinib in RP2D, Sintilimab and radiotherapy will be applied as before.
干预措施: Radiotherapy (Radiation)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: The objective response rate (ORR) will be evaluated before surgery.
The percentage of patients with objective response. Objective response is defined as complete response (CR) or partial response (PR) per response evaluation criteria (RECIST v1.1) before surgery.
次要结局
- Wound Complications(Up to 120 days from the surgery.)
- Local Control Rate(From the start of treatment to local recurrence, up to 5 years.)
- Quality of Life (QoL) according to the Musculoskeletal Tumor Society (MSTS)(Quality of Life (QoL) will be evaluated at least five times: before treatment, at 3, 6, 12 and 24 months respectively after surgery.)
- Quality of Life (QoL) according to the Short Form (SF)-36 questionnaires(Quality of Life (QoL) will be evaluated at least five times: before treatment, at 3, 6, 12 and 24 months respectively after surgery.)
- Non-Perfused Volume (NPV)(The non-perfused volume (NPV) will be measured in four weeks before preoperative treatment and before surgery in week18-21.)
- Adverse Events(From the beginning of treatment to 90 days after the end of the last treatment.)
- Quality of Life (QoL) according to the Toronto Extremity Salvage Score (TESS)(Quality of Life (QoL) will be evaluated at least five times: before treatment, at 3, 6, 12 and 24 months respectively after surgery.)
- Pathological Complete Response (pCR) and Near pCR Rate(The pathologic complete response (pCR) rate will be evaluated from surgical samples, immediately after surgery.)
- Progression-Free Survival (PFS)(Up to 5 years)
- Overall Survival (OS)(Up to 5 years)