Clinical trial NCT04356872: The Combination of Sintilimab and AI (Doxorubicin, ADM/Ifosfamide, IFO) for the First Line Treatment of Select Type of Metastatic/Unresectable Soft Tissue Sarcoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Sarcoma, Soft Tissue
Keywords: PD-1
doxorubicin
ifosfamide
first line treatment
Lead sponsor: Fudan University
Sponsor class: OTHER
Collaborators: name: Zhejiang Cancer Hospital
name: Tongji Hospital
name: Xijing Hospital
name: Shanghai Zhongshan Hospital
First posted: 2020-04-22
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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;

Primary outcomes:
measure: overall response rate, ORR
timeFrame: up to two years
Secondary outcomes:
measure: progression free survival, PFS
timeFrame: up to three years
measure: adverse events, AE
timeFrame: up to three years
measure: overall survival, OS
timeFrame: up to three years
Other outcomes:
measure: PD-L1 expression
timeFrame: up to two years
measure: tumor infiltrating lymphocytes measurement
timeFrame: up to two years
Locations:
city: Shanghai
country: China
facility: Fudan University, Cancer Hospital
state: Shanghai
Study officials:
References: