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

Sarcoma, Soft Tissue Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04356872
• Other study ID #: SAIS
• Status: Recruiting
• Phase: Phase 2
• Start date: April 8, 2020
• Est. completion date: March 30, 2023

Study information

• Verified date: July 2020
• Source: Fudan University
• Contact: Xin Liu, MD
• Phone: 0086-021-64175590
• Email: jeanettexin[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: March 30, 2023
• Est. primary completion date: March 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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;

Related Conditions & MeSH terms

• Sarcoma
• Sarcoma, Soft Tissue

Intervention

Drug:
• Sintilimab
immune check point inhibitor, 200mg, iv, d1
• Doxorubicin Hydrochloride
ADM, 60mg/m2, iv, d1
• Ifosfamide
IFO, 1.8 g/m2/d, d1-5

Locations

Country	Name	City	State
China	Fudan University, Cancer Hospital	Shanghai	Shanghai

Sponsors (5)

Lead Sponsor	Collaborator
Fudan University	Shanghai Zhongshan Hospital, Tongji Hospital, Xijing Hospital, Zhejiang Cancer Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	PD-L1 expression	PD-L1 expression will be detected by Immunohistologic chemistry, IHC or PCR method	up to two years
Other	tumor infiltrating lymphocytes measurement	tumor infiltrating lymphocytes will be measured by flowcytometry using tissue and/or peripheral blood sample;	up to two years
Primary	overall response rate, ORR	the best response rate	up to two years
Secondary	progression free survival, PFS	from first dose treatment to disease progression	up to three years
Secondary	adverse events, AE	treatment related adverse events, TRAEs	up to three years
Secondary	overall survival, OS	overall survival	up to three years