Apatinib Combined With Liposomal Irinotecan for Refractory or Metastatic Osteosarcoma

March 15, 2026 updated by: Xie Lu, Peking University People's Hospital

Safety and Efficacy of Apatinib Combined With Irinotecan Liposome Injection in the Treatment of Recurrent or Metastatic Osteosarcoma: A Single-Arm, Open-Label, Prospective Multicenter Clinical Study

In advanced osteosarcoma where traditional chemotherapy has failed, the multi-targeted tyrosine kinase inhibitor apatinib has become a mainstream systemic treatment option in China. However, for patients with a high tumor burden or extra-pulmonary lesions, these drugs are prone to secondary resistance, necessitating combination with chemotherapy for more effective comprehensive control. Liposomal irinotecan, a newly approved topoisomerase inhibitor, exhibits lower toxicity compared to traditional irinotecan and is one of the second-line chemotherapy agents for osteosarcoma, making it a suitable candidate for combination therapy with apatinib.

The primary objective of this study is to determine the optimal regimen of apatinib combined with liposomal irinotecan injection, while the secondary objective is to evaluate the safety and efficacy of this combination in patients with refractory osteosarcoma who have progressed after second-line chemotherapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Osteosarcoma is the most common primary malignant bone tumor in adolescents and young adults. Although multimodal treatment including surgery and multi-agent chemotherapy has improved survival for patients with localized disease, the prognosis of patients with recurrent or metastatic osteosarcoma remains poor.

Targeting tumor angiogenesis has emerged as a promising therapeutic strategy for osteosarcoma. Apatinib is an oral small-molecule tyrosine kinase inhibitor that selectively inhibits VEGFR-2 and has demonstrated clinical activity in advanced osteosarcoma in previous studies.

Irinotecan is a topoisomerase I inhibitor with antitumor activity in several malignancies. Liposomal irinotecan is a nanoliposomal formulation that improves the pharmacokinetic profile and intratumoral delivery of irinotecan, potentially enhancing its antitumor effect.

This investigator-initiated study is designed to evaluate the safety, tolerability, and preliminary efficacy of apatinib combined with liposomal irinotecan in patients with recurrent or refractory osteosarcoma. Patients will receive oral apatinib daily in combination with intravenous liposomal irinotecan administered every two weeks until disease progression, unacceptable toxicity, or withdrawal of consent.

The primary objective is to evaluate the safety and tolerability of the combination therapy. Secondary objectives include evaluation of antitumor activity such as objective response rate, progression-free survival, and overall survival.

Study Type

Interventional

Enrollment (Estimated)

56

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Beijing, China
        • Recruiting
        • Peking University People's Hospital
        • Contact:
          • Peking University People's Hospital Lu Peking University People's Hospital
          • Phone Number: 86+01086491441
          • Email: xie.lu@hotmail.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. The subject or their legal representative must sign a written informed consent form prior to enrollment.
  2. Diagnosis of refractory osteosarcoma confirmed by histopathology. Pathological confirmation is mandatory for localized tumors and isolated pulmonary lesions; it is not required for multiple pulmonary metastases.
  3. Disease progression after standard, adequate first-line and second-line chemotherapy regimens for osteosarcoma, or progression within 6 months of stopping such therapy.
  4. At least one measurable target lesion according to RECIST version 1.1 criteria.
  5. ECOG Performance Status score of 0 or 1, with an expected survival of ≥3 months.
  6. Recovery from prior therapies: all side effects (except alopecia) must have resolved to Grade 1 or lower per NCI-CTCAE version 5.0.
  7. Adequate organ function as indicated by the following peripheral blood counts and serum biochemistry results
  8. Women of childbearing potential must agree to use effective contraception (e.g., intrauterine device, oral contraceptives, or condoms) during the study and for 6 months after study completion; they must have a negative serum or urine pregnancy test within 7 days prior to study enrollment and must not be breastfeeding. Male participants must agree to use effective contraception or have undergone surgical sterilization during the study and for 6 months after its completion.

Exclusion Criteria:

  1. Prior treatment with apatinib.
  2. Prior use of irinotecan or other analogues of topoisomerase inhibitors.
  3. Known allergic reactions, hypersensitivity, or intolerance to apatinib, liposomal irinotecan, or any of their excipients.
  4. Within 3 weeks after the last dose of any prior therapy, including systemic cytotoxic drug therapy, targeted therapy, radiotherapy, immunotherapy, or any other investigational therapy.
  5. Diagnosis of other malignancies within the past 3 years, except for adequately treated cutaneous basal cell carcinoma, carcinoma in situ of the cervix, or breast cancer that has undergone radical resection and remained disease-free for >3 years.
  6. Patients with known brain metastasis, spinal cord compression, carcinomatous meningitis, or those with imaging evidence of leptomeningeal disease or unstable brain lesions detected by CT or MRI during screening.
  7. Patients with symptomatic serous cavity effusions (e.g., pleural effusion, ascites, or pericardial effusion) requiring surgical intervention.
  8. Uncontrolled hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg despite optimal medical therapy).
  9. Other poorly controlled diseases.
  10. Participation in clinical trials of other antitumor drugs within the 4 weeks prior to enrollment.
  11. Treatment with strong CYP3A4 inhibitors within 7 days prior to study participation, or treatment with strong CYP3A4 inducers within 12 days prior to study participation.
  12. Patients currently receiving concurrent antitumor therapy.
  13. Patients with target lesions having previously received radiotherapy, but without subsequent progression.
  14. Patients who have received any vaccination during the treatment period, or have received an adenovirus-based vaccine within 4 weeks.
  15. Lactating women.
  16. Any condition that, in the investigator's judgment, may compromise the subject's well-being or ability to comply with or fulfill the study requirements.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Apatinib + Liposomal Irinotecan
Patients receive apatinib orally once daily in combination with liposomal irinotecan administered intravenously every week until disease progression or unacceptable toxicity.
Drug: Liposomal Irinotecan
Intravenous liposomal irinotecan administered on Day 1, 8, and 15 of each 3-week cycle.
Drug: Apatinib in arm1
Oral VEGFR-2 tyrosine kinase inhibitor administered in combination with liposomal irinotecan.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recommended Phase II Dose (RP2D)
Time Frame: 6 weeks
Determination of the recommended phase II dose based on dose-limiting toxicity (DLT) observed during the first two cycles (6 weeks).
6 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Objective Response Rate (ORR)
Time Frame: Every 6 weeks up to 24 months
Every 6 weeks up to 24 months
Progression-Free Survival (PFS)
Time Frame: From treatment initiation until disease progression or death, up to 24 months
From treatment initiation until disease progression or death, up to 24 months
Overall Survival，OS
Time Frame: From treatment initiation until death from any cause, up to 24 months
From treatment initiation until death from any cause, up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University People's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 5, 2026

Primary Completion (Estimated)

March 5, 2027

Study Completion (Estimated)

January 1, 2028

Study Registration Dates

First Submitted

March 6, 2026

First Submitted That Met QC Criteria

March 15, 2026

First Posted (Actual)

March 18, 2026

Study Record Updates

Last Update Posted (Actual)

March 18, 2026

Last Update Submitted That Met QC Criteria

March 15, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PKUPH-sarcoma 24

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Osteosarcoma

Clinical Trials on Liposomal Irinotecan

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Spain

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe