The Combination of Sintilimab and AI (Doxorubicin, ADM/Ifosfamide, IFO) for the First Line Treatment of Select Type of Metastatic/Unresectable Soft Tissue Sarcoma

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Sarcoma, Soft Tissue

Intervention / Treatment
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* Drug: Sintilimab
* Drug: Doxorubicin Hydrochloride
* Drug: Ifosfamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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)； Exclusion Criteria: 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;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment<br>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. | Drug: Sintilimab<br>* immune check point inhibitor, 200mg, iv, d1<br>Drug: Doxorubicin Hydrochloride<br>* ADM, 60mg/m2, iv, d1<br>* Other names: ADM;Drug: Ifosfamide<br>* IFO, 1.8 g/m2/d, d1-5<br>* Other names: IFO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response rate, ORR | the best response rate | up to two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival, PFS | from first dose treatment to disease progression | up to three years | 
| adverse events, AE | treatment related adverse events, TRAEs | up to three years | 
| overall survival, OS | overall survival | up to three years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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doxorubicin, PD-1, ifosfamide, first line treatment