A Prospective Phase Ib/II Trial of Preoperative Radiotherapy Combined With Chemotherapy and Immunotherapy in High-Risk Localized Soft Tissue Sarcoma
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, chemotherapy and immunotherapy in patients with high-risk localized soft tissue sarcoma.
There will be 52 patients with high-risk localized extremity and trunk soft tissue sarcoma recruited. The trail is designed as a two-stage study. In safety lead-in phase (phase Ib), using 3+3 design, 4 cycles of Pegylated Liposomal Doxorubicin (37.5 mg/m2, 30 mg/m2, q3w) or doxorubicin hydrochloride (75mg/m2, q3w), Sintilimab (200mg, q3w) and radiotherapy (BED=50-60Gy (α/β=10)) will be applied. In phase II, Pegylated Liposomal Doxorubicin 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed STS, G2 or G
- •The histological types include: pleomorphic undifferentiated sarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, myxofibrosarcoma, fibrosarcoma, angiosarcoma but not radiotherapy-induced angiosarcoma, etc.
- •Has>5 cm lesions, or the lesions are determined to be borderline resectable or unresectable by a multidisciplinary consultation.
- •Has imaging-confirmed localized lesions on the limbs or trunk without distant metastases.
- •Experience primary tumor or local recurrence after surgery (disease-free survival more than 2 months after surgery)
- •Aged from 18 to 70, with ECOG performance status 0-1, or aged from 70 to 75, with ECOG performance status
- •Has life expectancy more than 2 years
- •Demonstrate adequate organ function (bone marrow, liver, and kidney function) (Leukocytes ≥ 3 × 10^9 /L, Neutrophils ≥ 1.5 × 10^9 /L, Hemoglobin ≥ 90 g/L, Platelet count ≥ 100 × 10^9 /L, Total bilirubin ≤1.5 × institutional upper limit of normal (ULN), Aspartate transaminase ≤2.5 × ULN, Alanine transaminase ≤2.5 × ULN, Serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min.)
- •Fully informed and willing to provide written informed consent for the trial.
排除标准
- •The presences of regional or distant metastases detected by imaging evaluation
- •Patients with the following histological types: osteosarcoma, chordoma, classical chondrosarcoma, Kaposi's sarcoma, malignant mesothelioma, radiation-induced sarcomas.
- •Known 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 five years)
- •Known history of other chemotherapy within 4 weeks before enrolment, previous anti-PD1 treatment, previous radiotherapy in the radiation field, or has other contraindications to radiotherapy or surgery.
- •Uncontrolled hyperglycaemia or Coagulation disorder
- •Active infection requiring systemic anti-infective therapy
- •Previous major surgery within 2 weeks before enrolment (excluding minor operation such as diagnostic biopsy or peripherally inserted central catheter implantation)
- •Known history of immunodeficiency diseases or active autoimmune disease requiring systemic treatment
- •Female patients pregnant or breastfeeding, Male patients expecting to have babies
研究组 & 干预措施
Treatment Arm
There will be 52 patients with high-risk localized extremity and trunk soft tissue sarcoma recruited.
In safety lead-in phase (phase Ib): using 3+3 design, patients will receive 4 cycles of Pegylated Liposomal Doxorubicin or doxorubicin hydrochloride, sintilimab and radiotherapy.
In phase II: Pegylated Liposomal Doxorubicin in RP2D, sintilimab and radiotherapy will be applied as before.
干预措施: Doxorubicin (Drug)
Treatment Arm
There will be 52 patients with high-risk localized extremity and trunk soft tissue sarcoma recruited.
In safety lead-in phase (phase Ib): using 3+3 design, patients will receive 4 cycles of Pegylated Liposomal Doxorubicin or doxorubicin hydrochloride, sintilimab and radiotherapy.
In phase II: Pegylated Liposomal Doxorubicin in RP2D, sintilimab and radiotherapy will be applied as before.
干预措施: Anti-PD-1 monoclonal antibody (Drug)
Treatment Arm
There will be 52 patients with high-risk localized extremity and trunk soft tissue sarcoma recruited.
In safety lead-in phase (phase Ib): using 3+3 design, patients will receive 4 cycles of Pegylated Liposomal Doxorubicin or doxorubicin hydrochloride, sintilimab and radiotherapy.
In phase II: Pegylated Liposomal Doxorubicin in RP2D, sintilimab and radiotherapy will be applied as before.
干预措施: Radiotherapy (Radiation)
Treatment Arm
There will be 52 patients with high-risk localized extremity and trunk soft tissue sarcoma recruited.
In safety lead-in phase (phase Ib): using 3+3 design, patients will receive 4 cycles of Pegylated Liposomal Doxorubicin or doxorubicin hydrochloride, sintilimab and radiotherapy.
In phase II: Pegylated Liposomal Doxorubicin in RP2D, sintilimab and radiotherapy will be applied as before.
干预措施: Pegylated Liposomal Doxorubicin (Drug)
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, which will be scheduled 5-12 weeks after the last fraction of radiotherapy.
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
- Non-Perfused Volume (NPV)(The non-perfused volume (NPV) will be measured in four weeks before preoperative treatment and before surgery, which will be scheduled 5-12 weeks after the last fraction of radiotherapy.)
- Pathological Complete Response (pCR) and Near pCR Rate(The pathologic complete response (pCR) rate will be evaluated from surgical samples, immediately after surgery.)
- Acute Adverse Events(through study completion, an average of 6 months.)
- Wound Complications(Up to 120 days from the surgery.)
- 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.)
- Progression-Free Survival (PFS)(Up to 5 years)
- Overall Survival (OS)(Up to 5 years)
- Local Control Rate(Up to 5 years)
- 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.)
- 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.)