Utidelone Capsules Combined With Doxorubicin for Advanced Soft Tissue Sarcoma

Prior treatment

• Within the 3 years prior to enrollment, the participant had suffered from other malignant tumors, excluding cured cases of skin basal cell carcinoma or skin squamous cell carcinoma, cervical carcinoma in situ, or thyroid papillary carcinoma.
• The participant had previously received anthracycline-based treatment, or had contraindications to doxorubicin treatment (the relevant contraindications can be found in the doxorubicin instructions), or was assessed by the investigator as not suitable for doxorubicin treatment.
• Participants with previous use of oltiderone.
• Within 2 weeks prior to enrollment, the participant had received traditional Chinese medicine or Chinese patent medicine with anti-tumor indications; within 2 weeks prior to enrollment, the participant had received local radiotherapy.
• Within 4 weeks prior to enrollment, the participant had undergone major surgical treatment, significant traumatic injury, or planned to undergo major surgery during the study period, or had long-standing unhealed wounds or fractures.
• Planned to receive surgical treatment, radiotherapy, or other systemic anti-tumor therapy for soft tissue sarcoma during the study.
• The adverse effects of previous antineoplastic therapy have not recovered to CTCAE 5.0 grade ≤1 (except for toxicities without safety risk judged by investigators, such as alopecia).
• Participants with symptomatic/uncontrolled central nervous system metastases or leptomeningeal metastases, including but not limited to participants with confirmed progressive brain metastases on imaging 2 months after radiotherapy or other local therapies, or participants deemed ineligible for enrollment by the investigator.
• History of severe cardiovascular and cerebrovascular diseases, including but not limited to:
  • Severe cardiac rhythm or conduction abnormalities, such as clinically significant ventricular arrhythmias requiring intervention, second- or third-degree atrioventricular block; history of myocardial infarction, coronary angioplasty, or coronary artery bypass grafting; average QTcF ≥450 ms (male)/QTcF ≥470 ms (female) from three 12-lead ECGs at rest \[see formula in Appendix 3\]; New York Heart Association (NYHA) Class II-IV heart failure;
  • Stroke or other Grade ≥3 cerebrovascular events within 3 months prior to enrollment; or symptomatic cerebral infarction;
  • Clinically uncontrolled hypertension;
  • Past or current other high-risk cardiovascular and cerebrovascular diseases deemed to interfere with this trial by the investigator.
• Within the previous 4 weeks prior to enrollment, participants had participated in another interventional clinical study or received treatment from other studies (participants who have completed other study treatments and are currently in the follow-up period are allowed to enroll in this study).

Other illness

• Tumor with active bleeding.
• Uncontrolled bone metastases, defined as participants with existing or imminent fracture risk, requiring surgery or local radiotherapy in the near term, or with other critical conditions as assessed by the investigator.
• Participants with gastrointestinal diseases such as esophageal obstruction, pyloric obstruction, intestinal obstruction, or status post gastrointestinal resection, or other factors causing dysphagia that affect oral drug administration and absorption.
• Participants with active infection requiring current systemic anti-infective therapy.
• Participants with psychiatric disorders or poor compliance.

Lab values

• Participants with other severe systemic diseases or abnormal laboratory findings that render them unsuitable for participation in this study as judged by the investigator.

Other

• Tumor subtypes including gastrointestinal stromal tumor, non-pleomorphic rhabdomyosarcoma, undifferentiated small round cell sarcoma, desmoplastic small round cell tumor, alveolar soft part sarcoma, clear cell sarcoma, etc.
• CTCAE 5.0 grade \> 1 for symptomatic peripheral neuropathy.
• Participants with uncontrolled pleural effusion or ascites requiring repeated drainage (once monthly or more frequently), and moderate or greater pericardial effusion.
• Pregnancy (positive pregnancy test) or lactation.

• Fully understand the purpose, content, process of the trial and possible adverse reactions, voluntarily participate as a subject, and sign the informed consent form;
• Age of 18-70 years old (including 18 and 70 years old) at the time of informed consent (ICF) signing, regardless of gender.
• Histopathologically /cytologically confirmed unresectable locally advanced or metastatic soft tissue sarcoma (classified per the 5th WHO classification, including leiomyosarcoma, liposarcoma, angiosarcoma, epithelioid sarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, malignant peripheral nerve sheath tumor, myxofibrosarcoma, pleomorphic rhabdomyosarcoma, etc.).
• No prior systemic anti-tumor therapy for advanced soft tissue sarcoma. For participants with prior neoadjuvant or adjuvant therapy, disease progression must occur \>6 months after the last treatment.
• At least one measurable lesion according to RECIST v1.1 definition.
• ECOG performance status of 0 or 1, with an expected survival of more than 12 weeks.
• Within 1 week before enrollment, the participant's blood routine examination was basically normal, and within 2 weeks before enrollment, the participant did not receive recombinant human granulocyte colony-stimulating factor (rhG-CSF) or blood products/erythropoietin (EPO).
  • Absolute neutrophil count (ANC) ≥1.5×10⁹/L;
  • Platelet count (PLT) ≥100×10⁹/L;
  • Hemoglobin ≥9.0 g/dL.
• Blood biochemical examination was basically normal within 1 week before enrollment.
  • Total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN);
  • Alanine aminotransferase (ALT) ≤3 × ULN (≤5 × ULN for participants with liver metastases);
  • Aspartate aminotransferase (AST) ≤3 × ULN (≤5 × ULN for participants with liver metastases).
• Left ventricular ejection fraction (LVEF) of echocardiography is ≥ 55%.
• Eligible participants of reproductive potential (male and female) must agree to use reliable contraception (hormonal, barrier methods or abstinence) together with their partner during the study period and for at least 6 months after the last study drug administration. Females of childbearing potential must have a negative serum or urine pregnancy test prior to enrollment.