Apatinib With Ifosfamide Plus Etoposide for Relapsed or Refractory Osteosarcoma (OAIE)

Phase 2

Completed

• Conditions: Effect of Drug; Drug; Toxicity
• Interventions: Drug: Apatinib+IE; Drug: IE

• Registration Number: NCT05277480
• Lead Sponsor: Peking University People's Hospital

Brief Summary

Apatinib has led to positive responses in the treatment of osteosarcoma refractory to first-line chemotherapy. However, apatinib demonstrates only short-lived activity, and the disease control of musculoskeletal lesions is worse than that of pulmonary lesions. This treatment failure has been partly overcome by the addition of ifosfamide and etoposide (IE). We have ever retrospectively compared the activity of apatinib + IE in relapsed or refractory osteosarcoma in two sarcoma centers in China and concluded that for osteosarcoma with multiple sites of metastasis, apatinib + IE demonstrated clinically meaningful antitumor activity and delayed disease progression in patients with recurrent or refractory osteosarcoma after failure of chemotherapy. However to overcome the influence of other interventions on the outcome, we are currently performing a prospective trial to investigate this combination, from which more accurate data on this treatment strategy are expected.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-03-01
• Study First Submitted: 2022-03-03
• Study First Submitted QC: 2022-03-03
• Study First Posted: 2022-03-14
• Primary Completion: 2023-06-30
• Study Completion: 2023-11-26
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-29
• Last Update Posted: 2024-07-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 81

Inclusion Criteria

1. advanced recurrent and refractory osteosarcoma confirmed by histopathology;
2. initial treatment in the Orthopedic/Oncology Departments of Peking University People's Hospital or Peking University Shougang Hospital;
3. progression less than 6 months after first-line chemotherapy with a combination of high-dose methotrexate, doxorubicin, cisplatin and ifosfamide (first-line chemotherapy);
4. measurable lesions according to the Response Evaluation Criteria for Solid Tumors (RECIST 1.1) ;
5. Eastern Cooperative Oncology Group performance status ≤ 1 ;
6. acceptable haematologic, hepatic, and renal function.

Exclusion Criteria

1. those who had been previously treated with antiangiogenic TKIs and single IE chemotherapy;
2. those who had severe or uncontrolled medical disorders that could jeopardize the outcomes of the study. These confounding conditions included, cardiac clinical symptoms or disease with left ventricular ejection fraction<50%, and hypertension that could not be well controlled with antihypertensive drugs.;
3. all patients were assessed by the sarcoma board including a thoracic surgeon with at least 10 years surgical experience. Patients with lung metastases only were carefully assessed for eligibility for metastasectomy, of whom those who were suitable for surgery were excluded from this study;
4. weight loss of 20% or more before illness;
5. brain or leptomeningeal metastasis;
6. surgical procedure or radiotherapy within 4 weeks of enrollment;
7. activegastroduodenal ulcer, previous condition associated with risk of bleeding or requiring anticoagulation;
8. proteinuria or hematuria, denutrition with albuminemia <25 g/L;
9. women who were pregnant or breast feeding, other malignancy;
10. positive HBV/HCV/HIV serology, and known allergy to the experimental agents.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Apatinib+IE group	Apatinib+IE	IE: Ifosfamide Plus Etoposide
IE group	IE	IE: Ifosfamide Plus Etoposide

Primary Outcome Measures

Name	Time	Method
Progression free survival	2 years	from the start of target treatment until disease progression or death, whichever came first.

Secondary Outcome Measures

Name	Time	Method
Overall survival	3 years	from the date of treatment initiation to death from any cause.

Trial Locations

Locations (4)

Peking University People's Hospital; 🇨🇳 Beijing, Beijing, China

Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University; 🇨🇳 Nanjing, Jiangsu, China

Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China

Shanghai Jiao Tong University Affiliated Sixth People's Hospital; 🇨🇳 Shanghai, Shanghai, China