The Combination of Sintilimab and AI (Doxorubicin, ADM/Ifosfamide, IFO) for the First Line Treatment of Select Type of Metastatic/Unresectable Soft Tissue Sarcoma
Phase 2
- Conditions
- Sarcoma, Soft Tissue
- Interventions
- Registration Number
- NCT04356872
- Lead Sponsor
- Fudan University
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 45
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;
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description treatment Sintilimab 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. treatment Doxorubicin Hydrochloride 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. treatment Ifosfamide 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.
- Primary Outcome Measures
Name Time Method overall response rate, ORR up to two years the best response rate
- Secondary Outcome Measures
Name Time Method progression free survival, PFS up to three years from first dose treatment to disease progression
adverse events, AE up to three years treatment related adverse events, TRAEs
overall survival, OS up to three years overall survival
Trial Locations
- Locations (1)
Fudan University, Cancer Hospital
🇨🇳Shanghai, Shanghai, China