Apatinib plus liposomal irinotecan for refractory or metastatic osteosarcoma

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

This trial tests whether combining the oral drug apatinib with intravenous liposomal irinotecan helps patients whose osteosarcoma has progressed after standard chemotherapy.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 56 (estimated)
• Ages: 12 Years to 65 Years
• Sex: All
• Sponsor: Peking University People's Hospital (Academic / other)
• Drugs / interventions: apatinib, chemotherapy, immunotherapy
• Locations: 1 site (Beijing)
• Trial ID: NCT07479732 on ClinicalTrials.gov

What this trial studies

This phase 1/2, investigator-initiated trial at Peking University People's Hospital combines daily oral apatinib with intravenous liposomal irinotecan given every two weeks in patients with refractory or metastatic osteosarcoma after prior first- and second-line chemotherapy. The phase 1 portion will identify the optimal dose/regimen and characterize safety and tolerability, while the phase 2 portion will measure preliminary antitumor activity including objective response rate, progression-free survival, and overall survival. Eligible participants must have measurable disease by RECIST v1.1, ECOG performance status 0–1, and adequate organ function, and treatment continues until progression, unacceptable toxicity, or withdrawal. The trial targets patients with high tumor burden or extrapulmonary lesions where single-agent antiangiogenic therapy often leads to secondary resistance.

Who should consider this trial

Good fit: Adults with histologically confirmed refractory or metastatic osteosarcoma who progressed after standard first- and second-line chemotherapy, have at least one measurable lesion, ECOG 0–1, and adequate organ function are ideal candidates.

Not a fit: Patients with poor performance status (ECOG ≥2), uncontrolled organ dysfunction, or intolerance to tyrosine kinase inhibitors or irinotecan are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could provide better tumor control and longer progression-free survival for patients whose osteosarcoma no longer responds to standard chemotherapy.

How similar studies have performed: Single-agent apatinib has shown activity in advanced osteosarcoma in prior reports and liposomal irinotecan has improved pharmacokinetics, but this specific combination is relatively novel and not yet widely tested.

Eligibility criteria

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.

Where this trial is running

Beijing

• Peking University People's Hospital — Beijing, China (Recruiting)

Study contacts

• Study coordinator: Xie Lu LuXie

Conditions Osteosarcoma; Osteosarcoma Metastatic