This is a phase 1/2 study evaluating safety, tolerability, and efficacy of Sulfatinib in combination with chemotherapy (ifosfamide and etoposide) in children and adolescents with refractory or relapsed osteosarcoma ( combination Sulfatinib).

The study consists of 2 cohorts:

Cohort 1 (Traditional chemotherapy) will evaluate the efficacy of ifosfamide and etoposide in children, adolescents, and young adults with relapsed or refractory osteosarcoma.

Cohort 2 (Combination Expansion) will evaluate the efficacy of Sulfatinib in combination with ifosfamide and etoposide in children, adolescents, and young adults with relapsed or refractory osteosarcoma.

Sulfatinib will be provided as hard capsules containing 300 mg Sulfatinib. Sulfatinib capsules should be dissolved in water or apple juice for those who are unable to swallow capsules.

Inclusion Criteria:

1. Osteosarcoma subjects Male or female participants aged 2 to 25 years at the time of informed consent(Histologically or cytologically confirmed diagnosis of high grade osteosarcoma)
2. Recurrent or refractory solid tumor malignancies that have treated with standard anticancer therapy but have no available treatment options.
3. Evaluable or measurable disease that met the following criteria: 1. Participants must have an evaluable or measurable disease based on RECIST 1.1, using computed tomography (CT)/ magnetic resonance imaging (MRI). 2. Lesions that have been treated locally, such as external beam radiation therapy (EBRT) or radiofrequency (RF) ablation, must subsequently grow clearly to be considered target lesions.
4. Life expectancy is 3 months or more.
5. Adequate bone marrow function : ①. Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L. ②. Hemoglobin ≥ 8.0 g/ deciliter (hemoglobin ≤ 8.0 g/ deciliter is acceptable if corrected by growth factors or transfusion before starting sovanitinib). ③. Platelet count ≥ 75 x 10^9/L.
6. Adequate liver function: 1. Bilirubin ≤ 1.5 times the upper limit of normal (ULN). 2. Alkaline phosphatase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 times of ULN.
7. Adequate renal function, such as creatinine clearance (or radioisotope glomerular filtration rate [GFR]), must be greater than 70 mL/min/ 1.73 square meters.

(8)A baseline left ventricular ejection fraction (LVEF) of 50% or greater, as determined by echocardiography, indicates adequate cardiac function.

(9) Good control of blood pressure (BP) with or without antihypertensive medication was defined as : blood pressure below 95% for sex, age, and height/length at screening (according to National Heart, Lung, and Blood Institute guidelines) and no change in antihypertensive medication during the cycle 1 of project. participants with osteosarcoma had blood pressure ≤150/90 mm Hg at screening and had no change in antihypertensive therapy during the cycle 1 of project.

(10)Parents or legal representative (guardian) shall sign the written informed consent and obtain the consent of minor participants. Written informed consent from subjects ≥18 years of age. Willing and able to abide by the researchers determine solutions, plans, and toxicity of follow-up management.

Exclusion Criteria:

1. Any active infection or infectious disease.
2. Any medical condition or other condition that the investigator believes will prevent the participant from participating in the clinical study.
3. Other organ toxicity (except hair loss) caused by previous anti-cancer treatment (research drug, chemotherapy or radiotherapy)
4. Known hypersensitivity to any component of the product (soventinib or ingredient).
5. Any other anti-tumor treatment is given at the same time.
6. He has been treated with sovantinib before.
7. Two or more previous VEGF/VEGFR targeted therapies.
8. Currently receiving any study drug or device in another clinical trial or within 30 days before informed consent.
9. Clinically significant ECG abnormalities, including significant baseline QT or QTc interval prolongation (e.g., QTc interval duplication is demonstrated to be greater than 480 milliseconds).
10. Gastrointestinal malabsorption or any other condition that the investigator believes may affect the absorption of sovantinib.
11. Gastrointestinal bleeding or active hemoptysis (at least half a teaspoon of bright red blood) occurred within 3 weeks before the first administration of the study drug.
12. Active second malignant tumor (excluding superficial melanoma, in situ, basal or squamous cell skin cancer with definite treatment) within 2 years before enrollment.
13. Previously treated with ifosfamide with nephrotoxicity or encephalopathy grade greater than or equal to grade 3.

Women who were breastfeeding or pregnant at the time of screening or baseline. If a negative screening pregnancy test is obtained more than 72 hours before the first administration of the study drug, a separate baseline assessment is required.

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