A Single Arm, Multi Centers, Phase II Study of Sintilimab, Doxorubicin and Ifosfamide at First-line Treatment of Soft Tissue Sarcoma Including Undifferentiated Pleomorphic Sarcoma, Synovial Sarcoma, Myxoid Liposarcoma and De-differentiated Liposarcoma
试验速览
- 阶段
- 2 期
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- overall response rate, ORR
研究概览
简要总结
This is a phase II trial to explore the feasibility of PD-1 immune check point inhibitor, sintilimab, in combination of stand of care chemotherapy in first-line treatment of selected soft tissue sarcoma.
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
- •Men and women aged 18-75 years;
- •Provide written informed consent;
- •Local advanced or metastatic unresectable sarcoma;
- •Histologically confirmed undifferentiated pleomorphic sarcoma, synovial sarcoma, de-differentiated liposarcoma and myxoid liposarcoma;
- •Performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale;
- •Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1;
- •Life span expectation over 3 months
- •Absolute neutrophil count (ANC) ≥1,500/mcL (within 7 days of treatment initiation) ；
- •Hemoglobin ≥9 g/dL (within 7 days of treatment initiation) ；
- •Platelets ≥ 90,000/mcL (within 7 days of treatment initiation) ；
- •Serum creatinine ≤ 1.5 X upper limit of normal (ULN) or creatinine clearance [CrCl]) ≥ 50 mL/min for subject with creatinine levels (within 7 days of treatment initiation) ；
- •Serum total bilirubin ≤ 1.5 X ULN (within 7 days of treatment initiation) ；
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 X ULN or =< 5 X ULN for subjects with liver metastases (within 7 days of treatment initiation)；
排除标准
- •Prior systemic therapy for advanced and metastatic disease, except adjuvant treatment（not received anthracycline）replase over 6 months;
- •Received any testing anti-cancer drugs within four weeks of treatment initiation;
- •Prior immune related therapy including but not limited to PD-1, PD-L1, CD137, CTLA4, T cell stimulation, check point inhibitor etc;
- •Symptomatic, untreated, or uncontrolled brain metastases present
- •clinical meaningful active bleeding;
- •Other malignant cancer history rather than soft tissue sarcoma within five year prior to treatment initiation;
- •Have active infections requiring therapy;
- •Have active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Patients that require inhaled steroids or local steroid injections would not be excluded from the study. Patients with hypothyroidism not from autoimmune disease that is stable on hormone replacement will not be excluded from the study.
- •Pregnant or breast-feeding；
- •Any serious or unstable medical condition or mental illness；
- •Serious systemic diseases such as heart disease, history of (non-infectious) pneumonitis;
- •Active HBV （>10000 copy/ml） and HCV （RNA> 1000copy/ml） infection；
- •Positive human immunodeficiency virus (HIV）or any acquired immunodeficiency syndrome, organ implantation;
研究组 & 干预措施
treatment
The patients with metastatic and unresectable soft tissue sarcoma including undifferentiated pleomorphic sarcoma, synovial sarcoma, de-differentiated liposarcoma and myxoid liposarcoma will be enrolled and given sintilimab (PD-1) , doxorubicin and doxorubicin every three weeks for 6 cycles followed by sintilimab mono therapy till disease progression. The first enrolled six patients is safety run-in step for observing drug-limiting toxicity (DLTs). If the combinatory treatment is intolerable, the doses of chemo regimens will be reduced according to drug instruction.
干预措施: Sintilimab (Drug)
treatment
The patients with metastatic and unresectable soft tissue sarcoma including undifferentiated pleomorphic sarcoma, synovial sarcoma, de-differentiated liposarcoma and myxoid liposarcoma will be enrolled and given sintilimab (PD-1) , doxorubicin and doxorubicin every three weeks for 6 cycles followed by sintilimab mono therapy till disease progression. The first enrolled six patients is safety run-in step for observing drug-limiting toxicity (DLTs). If the combinatory treatment is intolerable, the doses of chemo regimens will be reduced according to drug instruction.
干预措施: Doxorubicin Hydrochloride (Drug)
treatment
The patients with metastatic and unresectable soft tissue sarcoma including undifferentiated pleomorphic sarcoma, synovial sarcoma, de-differentiated liposarcoma and myxoid liposarcoma will be enrolled and given sintilimab (PD-1) , doxorubicin and doxorubicin every three weeks for 6 cycles followed by sintilimab mono therapy till disease progression. The first enrolled six patients is safety run-in step for observing drug-limiting toxicity (DLTs). If the combinatory treatment is intolerable, the doses of chemo regimens will be reduced according to drug instruction.
干预措施: Ifosfamide (Drug)
结局指标
主要结局
overall response rate, ORR
时间窗: up to two years
the best response rate
次要结局
- progression free survival, PFS(up to three years)
- adverse events, AE(up to three years)
- overall survival, OS(up to three years)
研究者
Zhiguo Luo, MD, PhD
Chief Clinical Professor
Fudan University