MAGNATE-S: A Phase 2 Exploratory Study of Paclitaxel Polymer Micelles Combined With Gemcitabine and Anti-Angiogenic TKIs (Lenvatinib or Anlotinib) for Advanced Bone and Soft Tissue Sarcomas
Design: This is an exploratory study, planning to enroll approximately 46 patients in total, divided into two separate groups (23 for bone sarcoma, 23 for soft tissue sarcoma). Process: Eligible and consenting patients will receive periodic combined drug therapy. Doctors will regularly evaluate efficacy and monitor safety through blood tests, US, CT, or MRI scans. Primary Goal: The main focus is to see how many patients experience significant tumor shrinkage (Objective Response Rate), and to record all adverse reactions that occur. Biomarker Research: To better understand treatment mechanisms and identify potential predictive markers, this study includes the collection of biological samples for future research, with careful design to minimize additional burden. Small extra blood samples will be collected during scheduled routine blood draws required for clinical monitoring. If a tumor biopsy or surgery is performed as part of necessary clinical care, the investigators will request permission to preserve a portion of the remaining tissue that would otherwise be discarded. These samples may be analyzed using techniques such as genetic or protein testing. What does this mean for participants? Potential Benefits: Participants have the opportunity to receive the new drug Paclitaxel Polymer Micelles free of charge and may benefit from it. Their participation will provide valuable treatment experience for all future patients with similar conditions. Potential Risks: The drug combination may increase the risk of certain side effects, such as fatigue, nausea, high blood pressure, hand-foot skin reactions, or decreased blood cell counts. The research team has developed detailed plans to prevent and manage these situations. Voluntary Principle: Participation is completely voluntary. Patients have the right to withdraw from the study at any time, for any reason, without affecting their right to receive other routine medical care. In summary, this study explores a regimen combining a novel nano-drug, chemotherapy, and precise targeted therapy, aiming to find a more effective and safer treatment option for patients with advanced bone and soft tissue sarcomas who have failed first-line treatment.
• 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.