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

Sponsor

Fudan University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04356872

Collaborator

Zhejiang Cancer Hospital (Other), Tongji Hospital (Other), Xijing Hospital (Other), Shanghai Zhongshan Hospital (Other)

Enrollment

Location

Arm

35.7

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma, Soft Tissue	Drug: Sintilimab Drug: Doxorubicin Hydrochloride Drug: Ifosfamide	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 8, 2020

Anticipated Primary Completion Date :

Mar 30, 2022

Anticipated Study Completion Date :

Mar 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Sintilimab immune check point inhibitor, 200mg, iv, d1 Drug: Doxorubicin Hydrochloride ADM, 60mg/m2, iv, d1 Other Names: ADM Drug: Ifosfamide IFO, 1.8 g/m2/d, d1-5 Other Names: IFO

Arm

Intervention/Treatment

Experimental: 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.

Drug: Sintilimab

immune check point inhibitor, 200mg, iv, d1

Drug: Doxorubicin Hydrochloride

ADM, 60mg/m2, iv, d1

Other Names:

ADM

Drug: Ifosfamide

IFO, 1.8 g/m2/d, d1-5

Other Names:

IFO

Outcome Measures

Primary Outcome Measures

overall response rate, ORR [up to two years]
the best response rate

Secondary Outcome Measures

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

Other Outcome Measures

PD-L1 expression [up to two years]
PD-L1 expression will be detected by Immunohistologic chemistry, IHC or PCR method
tumor infiltrating lymphocytes measurement [up to two years]
tumor infiltrating lymphocytes will be measured by flowcytometry using tissue and/or peripheral blood sample；

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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;