Paclitaxel polymer micelles with gemcitabine and targeted drugs for advanced sarcoma

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

This Phase 2 study tests whether combining a new paclitaxel formulation with gemcitabine and a targeted drug can help people with advanced or metastatic bone or soft tissue sarcoma that progressed after first-line chemotherapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 46 (estimated)
• Ages: 12 Years to 70 Years
• Sex: All
• Sponsor: Shanghai 6th People's Hospital (other)
• Drugs / interventions: chemotherapy, Lenvatinib, Anlotinib
• Locations: 1 site (Shanghai, CH)
• Trial ID: NCT07359053 on ClinicalTrials.gov

What this trial studies

This is a Phase 2 interventional trial that gives patients with locally advanced unresectable or metastatic bone or soft tissue sarcoma a combination regimen of paclitaxel polymer micelles plus gemcitabine together with a targeted oral agent chosen by tumor type (lenvatinib for bone sarcoma or anlotinib for soft tissue sarcoma). The study aims to improve tumor control while using a polymer micelle formulation of paclitaxel that may reduce allergic and other toxic reactions compared with conventional paclitaxel. Eligible patients must have histologically confirmed disease, measurable lesions per RECIST 1.1, prior progression after first-line chemotherapy, and acceptable organ function and performance status. Treatment, safety monitoring, and imaging follow-up will be conducted at the enrolling center to measure response and side effects.

Who should consider this trial

Good fit: Adults with histologically confirmed advanced or metastatic bone or soft tissue sarcoma, measurable disease, prior progression after first-line chemotherapy, ECOG 0–2, life expectancy of at least three months, and adequate organ function are candidates for this trial.

Not a fit: Patients with contraindications to paclitaxel polymer micelles, gemcitabine, or anti-angiogenic targeted agents, those with inadequate organ function, or those with very limited life expectancy or poor performance status are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, the regimen could offer better tumor control than current second-line options and may have a lower risk of severe allergic reactions thanks to the polymer micelle paclitaxel formulation.

How similar studies have performed: Previous combinations of taxanes or gemcitabine with anti-angiogenic agents have shown activity in some sarcoma subtypes, but the paclitaxel polymer micelle formulation and this specific drug pairing are relatively novel and less extensively studied.

Eligibility criteria

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:

  1. 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.)
  2. At least one measurable lesion per RECIST 1.1 criteria.
  3. Disease progression after prior first-line standard chemotherapy; ECOG performance status 0-2.
  4. Life expectancy ≥ 3 months.
  5. Willing and able to comply with study procedures, treatment, and follow-up.
  6. No contraindications to paclitaxel polymer micelles, gemcitabine, or small-molecule anti-angiogenic targeted agents.
* Physical Examination and Laboratory Results:

  1. 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.)
  2. 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).
  3. Adequate renal function: Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥ 50 mL/min.
  4. 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:

  1. Aged 12-70 years (male and female).
  2. 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.
  3. 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).

Where this trial is running

Shanghai, CH

• Shanghai Sixth Peolple'S Hospital — Shanghai, CH, China (RECRUITING)

Study contacts

• Study coordinator: Chenliang Zhou, MD

Conditions: Sarcoma, advanced sarcoma, Paclitaxel Polymer Micelles