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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Sarcoma, Soft Tissue
• Intervention / Treatment: Drug: Sintilimab; Drug: Doxorubicin Hydrochloride; Drug: Ifosfamide

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xin Liu, MD; Phone Number: 0086-021-64175590; Email: jeanettexin@hotmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Fudan University, Cancer Hospital
      • Contact: Xin Liu, MD; Phone Number: 0086-18017317720; Email: jeanettexin@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Zhejiang Cancer Hospital; Xijing Hospital; Shanghai Zhongshan Hospital; Tongji Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2020
• Primary Completion (Anticipated): March 30, 2022
• Study Completion (Anticipated): March 30, 2023

Study Registration Dates

• First Submitted: April 17, 2020
• First Submitted That Met QC Criteria: April 20, 2020
• First Posted (Actual): April 22, 2020

Study Record Updates

• Last Update Posted (Actual): July 14, 2020
• Last Update Submitted That Met QC Criteria: July 13, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: PD-1; doxorubicin; ifosfamide; first line treatment
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Ifosfamide; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: SAIS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: not yet decide, need to discuss with all collaborators

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No