Liposomal Irinotecan in Combination With Temozolomide and Bevacizumab in Patients With Advanced STS

A Study of Liposomal Irinotecan in Combination With Temozolomide and Bevacizumab in Patients With Relapsed or Refractory Soft Tissue Sarcoma

The study is expected to include 24 patients with metastatic or surgically unresectable relapsed/refractory soft tissue sarcoma confirmed by histological evidence, who have received at least one line of systemic treatment previously. The efficacy and safety of liposome irinotecan combined with temozolomide and bevacizumab in the treatment of relapsed/refractory soft tissue sarcoma will be evaluated.

Study Overview

• Status: Not yet recruiting
• Conditions: Soft Tissue Sarcoma (Excluding GIST)
• Intervention / Treatment: Drug: Irinotecan Hydrochloride Liposome Injection(II) combined with temozolomide and bevacizuma

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ying Dong; Phone Number: 0571 56978177; Email: dongying74@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • 2nd Affiliated Hospital, School of Medicine
      • Contact: Ying Dong; Phone Number: 0571-56978177; Email: dongying74@edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥14 years old, gender not limited;
2. For metastatic or surgically unresectable recurrent and refractory soft tissue sarcomas confirmed by histological evidence, this combination therapy regimen can be used as determined by the researcher.
3. Disease progression or intolerable toxicity has occurred after at least one line of systemic therapy (with or without targeted therapy) in the past.
4. At least one measurable lesion (RECIST v1.1);
5. ECOG: 0-2;
6. Expected survival period ≥3 months;
7. Good function of major organs, that is, meeting the following criteria (without receiving any blood components or cell growth factors within 14 days prior to randomization) :

Neutrophils ≥1.5*109/L; Platelet count ≥80*109/L; Hemoglobin ≥9g/dl; Serum albumin ≥3g/dl; (2) Total bilirubin ≤ 1.5 times the upper limit of the normal value (biliary drainage is allowed for biliary obstruction); ALT and AST≤ 3 times the upper limit of the normal value (for patients with liver metastasis, it can be relaxed to ≤ 5 times the upper limit of the normal value).

(3) Serum creatinine ≤ 1.5 times the upper limit of the normal value, creatinine clearance rate ≥60ml/min; (4) INR≤ 1.5 times the upper limit of the normal value and APTT≤ 1.5 times the upper limit of the normal value (screening can be conducted for anticoagulant therapy with stable doses such as low-molecular-weight heparin or warfarin and INR within the expected therapeutic range of the anticoagulant); (5) Electrocardiogram: QTcF≤450ms(for males), ≤470ms(for females); (6) Cardiac color Doppler ultrasound: LVEF (left ventricular ejection fraction) ≥50%; Women of childbearing age must undergo a blood pregnancy test within 3 days before randomization, and the result must be negative. They must also be willing to take appropriate contraceptive measures during the trial and for 6 months after the end of treatment. For men, it should be agreed to use appropriate methods of contraception during the study period and within 3 months after the end of treatment; 9. The subjects voluntarily joined this study and signed the informed consent form.

Exclusion Criteria:

1. Patients with known central nervous system metastases;
2. Severe gastrointestinal dysfunction (with bleeding, obstruction; inflammation above grade 2; diarrhea above grade 1);
3. Patients who have a history of treatment with irinotecan, temozolomide, bevacizumab or similar drugs;
4. Within the two weeks prior to randomization, there was third space effusion (such as a large amount of pleural effusion) that could not reach a stable state except for ascites (no intervention treatment is required after the drainage tube is removed);
5. Patients with ascites with clinical symptoms who require puncture or drainage, or those who have received ascites drainage within the past 3 months (except for those with only a small amount of ascites shown on imaging and controllable, but without clinical symptoms);
6. Currently accompanied by interstitial pneumonia or interstitial lung disease, or those with a history of interstitial pneumonia or interstitial lung disease requiring hormone therapy in the past, or other conditions that may interfere with the judgment and management of immune-related lung toxicity such as pulmonary fibrosis or organizing pneumonia (for example, Subjects with obliterative bronchiolitis, pneumoconiosis, drug-related pneumonia, idiopathic pneumonia, or those with active pneumonia or severely impaired lung function as shown by chest CT during the screening period; Active tuberculosis
7. Subjects with active autoimmune diseases or a history of autoimmune diseases that may relapse [including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism (subjects that can be controlled only through hormone replacement therapy can be enrolled)]; Those with skin diseases that do not require systemic treatment, such as vitiligo, psoriasis, alopecia, controlled type 1 diabetes treated with insulin, or childhood asthma that has been completely relieved and does not require any intervention in adulthood can be enrolled.
8. Known peripheral neuropathy (CTCAE≥ grade 3);
9. Known dihydropyrimidine dehydrogenase (low activity) or deficiency;
10. Severe infections (CTCAE > grade 2) occurred within 4 weeks prior to randomization, such as severe pneumonia requiring hospitalization, bacteremia, infectious complications, etc. There were symptoms and signs of infection within 2 weeks prior to randomization, requiring intravenous antibiotic treatment (except for prophylactic antibiotic use).

11. Have received any of the following treatments:

    The concomitant medication contained CYP3A4, CYP2C8 strong suppressor/strong inducer or UGT1A1 strong suppressor within 2 weeks prior to randomization; Use immunosuppressants or systemic hormones for immunosuppressive purposes within 2 weeks before randomization (dose >10mg/ day, prednisone or other equivalent therapeutic hormones); <s:1> Received radiotherapy within 2 weeks prior to randomization; Undergo major surgeries (such as thoracotomy, laparotomy, etc.) within 4 weeks before randomization; The patient has received any other clinical study drug treatment within 4 weeks prior to randomization, unless it is an observational (non-interventional) clinical study or follow-up of an interventional clinical study.

12. Abnormal coagulation function, with a bleeding tendency, or currently undergoing thrombolytic or anticoagulant therapy. Prophylactic use of low-dose aspirin (≤100mg/ day) and low-molecular-weight heparin (enoxaparin 40mg/ day and other low-molecular-weight heparin at equivalent doses) is permitted.
13. There are poorly controlled clinical symptoms or diseases of the heart, such as: (1) NYHA grade 2 or above heart failure; (2) Unstable angina pectoris; (3) Has suffered a myocardial infarction within six months; (4) Patients with clinically significant supraventricular or ventricular arrhythmias who require treatment or intervention;
14. Within the 3 years prior to randomization, the patient had a malignant tumor other than relapsed or refractory soft tissue sarcoma, excluding well-treated carcinoma in situ, cutaneous basal cell or squamous cell carcinoma, etc., which showed no signs of recurrence.
15. Individuals who are known to be allergic to irinotecan liposomes, other liposome products, temozolomide, bevacizumab, or any of the components in the above products;
16. Those who are known to have acquired immune deficiency syndrome (AIDS) or test positive for HIV, or are active syphilis carriers;
17. There is a clear history of neurological or mental disorders in the past, including epilepsy or dementia;
18. As determined by the researchers, the subjects have other factors that may force them to terminate the study halfway, such as non-compliance with the protocol, suffering from other serious diseases (including mental disorders) that require concurrent treatment, having severely abnormal laboratory test values of clinical significance, family or social factors that may affect the safety of the subjects or the collection of trial data, etc.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Irinotecan Hydrochloride Liposome Injection（II） combined with temozolomide and bevacizumab	Drug: Irinotecan Hydrochloride Liposome Injection(II) combined with temozolomide and bevacizuma; Irinotecan Hydrochloride Liposome Injection(II) : 56.5 mg/m2, intravenous infusion for 90 minutes (+30 minutes), day 1, 3 weeks as one study cycle; Clotemozolomide: 100 mg/m2/day × 5 days, with 3 weeks as one study cycle; Bevacizumab: 7.5 mg/kg, intravenous infusion, 1 day, 3 weeks as one study cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Progression-free survival (PFS) is a measure used in clinical trials and medical research to evaluate the effectiveness of treatments, especially in oncology. It refers to the length of time during and after treatment that a patient lives with a disease without it getting worse. In other words, PFS is the duration from the start of treatment until the disease progresses or until the patient dies from any caus，whichever came first, assessed up to 24 months	through study completion， assessed up to 24 months
Safety-Adverse events (AE)	Adverse events (AE)/serious adverse events (SAE) (judged based on NCI-CTCAE 5.0), etc.	through study completion，assessed up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	From the date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months	through study completion, an average of 1 year
12-week PFS rate	the percentage of patients who remain progression-free after 12 weeks treatment	12 weeks
overall survival	From the date of enrollment until the date of death from any cause or the end of the study, whichever came first, assessed up to 24 months	through study completion, an average of 2 years
Disease Control Rate (DCR）	From the date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months	through study completion, an average of 1 year
Duration of remission (DoR）	From the date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): March 31, 2026
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: February 5, 2026
• First Submitted That Met QC Criteria: March 4, 2026
• First Posted (Actual): March 9, 2026

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Sarcoma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Dacarbazine; Triazenes; Imidazoles; Temozolomide
• Other Study ID Numbers: 2025-1631

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No