Table 2 Inclusion and exclusion criteria of JCOG1802

(1) Histologically-proven STS

(2) H&E slides used for diagnosis of STS are available

(3) STS with metastatic disease (Stage IV in AJCC- TNM 8th edition), unresectable primary sarcoma, or unresectable recurrent sarcoma

(4) Disease progression confirmed within 6 months

(5) Disease to fulfill either following (i)-(iv), chemotherapy here including perioperative chemotherapy

(i) Disease progression during doxorubicin-based chemotherapy

(ii) Disease progression after termination of doxorubicin-based chemotherapy because of other than disease progression during chemotherapy

(iii) Local recurrence and/or metastasis of disease which has been disappeared by treatment including doxorubicin-based chemotherapy

(iv) Disease progression of residual disease after doxorubicin-based chemotherapy

(6) History of chemotherapy for sarcoma is only doxorubicin-based chemotherapy

(7) No treatment history for sarcoma and other cancers with trabectedin, eribulin or pazopanib

(8) Age 16 years or older

(9) ECOG (Eastern Cooperative Oncology Group) performance status (PS): 0–2

(10) Measurable or non-measurable disease

(11) Oral intake possible

(12) Adequate organ function as proved by the following laboratory studies within 14 days prior to registration; neutrophil count ≥ 1,500 /mm3; hemoglobin ≥ 8.0 g/dL; platelet count ≥ 100,000 /mm3; TB (total bilirubin) ≤ 1.5 mg/dL; AST ≤ 100 U/L; ALT ≤ 100 U/L; renal function to fulfill either following (a) or (b); (a) creatinine ≤ 1.5 mg/dL; (b) creatinine clearance ≥ 50 mL/min; ALP ≤ 900 U/L; CPK ≤ 600 U/L for men, ≤ 400 U/L for women; PT-INR ≤ 1.38; APTT ≤ 44.4 s; TSH: 0.5–4.5 micro unit/mL; FT4: 0.9–1.8 ng/dL

(13) Normal findings or no need of treatment on electrocardiogram (ECG) within 28 days prior to registration

(14) More than 50% of ejection fraction in echocardiography within 28 days prior to registration

(15) Written informed consent. If the patient's age is under 18 years old, the additional consent must be obtained from the patient's parent or legal guardian

(1) Synchronous or metachronous (within 2 years) malignancy except cancer with 95% or more of 2-year relative survival rate

(2) Diagnosed with active infectious disease requiring systemic treatment

(3) Febrile more than 38 degrees Celsius at the registration

(4) Pregnancy, possible pregnancy, within 28 days after delivery or breast-feeding, or male subjects who want pregnancy of their partner

(5) Psychological disorder difficult to participate in this study

(6) Receiving continuous systemic corticosteroid or immunosuppressant treatment (PO or IV)

(7) Systolic blood pressure > 140 mmHg and diastolic blood pressure > 90 mmHg in two consecutive times measured in a hospital on the day of registration (irrespective of antihypertensive agents use)

(8) Interstitial pneumonia, pulmonary fibrosis or severe emphysema confirmed on chest CT

(9) HBs antigen positive

(10) History of cardiovascular disease as follow;

(a) Myocardial infarction within the last 6 months, unstable angina pectoris within the last 3 weeks (b) Angioplasty surgery or stent implantation, or coronary artery bypass graft within 6 months (c) Heart failure class III or IV according to NYHA Classification (d) Uncontrolled valve disease, dilative cardiomyopathy, or hypertrophic myocardiopathy

(11) Active bleeding

(12) Symptomatic brain metastasis or brain metastasis requiring treatment (screening of brain metastasis is not required for clinically unnecessary patients)

(13) Pleural effusion, ascitic fluid, pericardial effusion requiring drainage