MAGNATE-S: Paclitaxel Polymer Micelles Combo in Advanced Sarcoma

Inclusion criteria

• Informed Consent: The subject has signed the informed consent form after receiving and understanding full explanation regarding the trial's purpose, procedures, anticipated efficacy, pharmacological actions, and risks.
• Target Population:

• Histologically confirmed advanced/metastatic bone or soft tissue sarcoma. (If recurrence or metastasis is not definitive, a biopsy with frozen section is recommended. Enrollment may proceed if frozen pathology suggests recurrence/metastasis.)
• At least one measurable lesion per RECIST 1.1 criteria.
• Disease progression after prior first-line standard chemotherapy; ECOG performance status 0-2.
• Life expectancy ≥ 3 months.
• Willing and able to comply with study procedures, treatment, and follow-up.
• No contraindications to paclitaxel polymer micelles, gemcitabine, or small-molecule anti-angiogenic targeted agents.
• Physical Examination and Laboratory Results:

• Adequate hematologic function: i) Absolute neutrophil count (ANC) ≥ 1.8 × 10⁹/L; ii) Platelet count ≥ 100 × 10⁹/L; iii) Hemoglobin ≥ 90 g/L. (If transfusions are given during screening, a repeat test after 1 week must meet these criteria.)
• Adequate hepatic function: i) Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ii) AST and ALT ≤ 2.5 × ULN (≤ 5 × ULN if liver metastases are present); Alkaline phosphatase (ALP) ≤ 5 × ULN (liver mets) or ≤ 10 × ULN (bone mets).
• Adequate renal function: Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥ 50 mL/min.
• Adequate coagulation: INR ≤ 1.5 × ULN and PT/aPTT ≤ 1.5 × ULN, unless on stable anticoagulant therapy.
• Hepatitis B: Subjects positive for HBsAg are eligible if, in the investigator's judgment, their chronic hepatitis B is stable and does not increase the subject's risk.
• Cardiac Function: No symptomatic cardiac insufficiency at baseline (NYHA class ≤ II) and no clinically significant ECG abnormalities.
• Age and Reproductive Status:

• Aged 12-70 years (male and female).
• Subjects of childbearing potential must agree to use effective contraception during the trial. A negative serum or urine pregnancy test within 24 hours before chemotherapy is required for women of childbearing potential.
• Female subjects must not be breastfeeding.

Exclusion criteria

• Known allergy or intolerance to any component or excipient of the investigational products.
• Primary brain tumor or central nervous system (CNS) metastases (including leptomeningeal metastases), except for a single, well-controlled, asymptomatic brain metastasis. CNS tumors still presenting with increased intracranial pressure or neuropsychiatric symptoms after treatment.
• Uncontrolled acute or chronic infections, or other severe concurrent medical conditions.
• History of other malignancies within the past 5 years, except for cured basal cell carcinoma of the skin or carcinoma in situ of the cervix.
• Active hepatitis or hepatic tumor burden exceeding 50% of the total liver volume.
• Uncontrolled third-space fluid accumulation not manageable by drainage (e.g., moderate to large pleural effusion, pericardial effusion, or ascites). Minimal asymptomatic fluid not requiring intervention may be allowed upon strict review.
• Psychiatric illness or cognitive impairment leading to poor compliance or inability to cooperate and report treatment responses.
• Severe organic disease or major organ failure (e.g., decompensated heart or lung failure) precluding tolerance to chemotherapy.
• Coagulopathy (INR >1.5, APTT >1.5 × ULN), bleeding tendency (e.g., active gastric ulcer, stool occult blood [++], hematemesis and/or melena within the past 3 months, hemoptysis), or tumor proximity to major blood vessels.
• Coronary artery disease above grade I, arrhythmia (including QTc interval >450 ms for males, >470 ms for females), use of antiarrhythmic medication, or relevant underlying cardiac disease/cardiac insufficiency.
• Renal insufficiency, history of renal disease, or proteinuria (urine protein ≥2+ or 24-hour urine protein >1.0 g).
• History of organ transplantation.
• History of substance abuse, chronic alcoholism, or infectious diseases such as AIDS.
• Long-term use of corticosteroids or immunosuppressants.
• Vaccination with live or attenuated vaccines (e.g., measles, mumps, rubella, varicella, yellow fever, rabies, BCG, oral typhoid) within 4 weeks prior to enrollment, or planned vaccination during the study. COVID-19 vaccination is permitted.
• Active hepatitis B (HBV DNA ≥1×10⁴ copies/mL or ≥2000 IU/mL) or hepatitis C (HCV RNA ≥15 IU/mL) infection; positive HIV antibody (unless clinically indicated); or positive syphilis antibody (TPPA).
• Any other condition deemed by the investigator to prevent completion of the trial or render the subject unsuitable (e.g., tumors like GIST or ALK-mutant inflammatory myofibroblastic tumor unsuitable for this chemotherapy regimen).