The aim of this study is to evaluate the efficacy and safety of Second-line chemotherapy combined with Apatinib for the patients with resectable pulmonary metastasis of osteosarcoma.
After standard chemotherapy and surgery for the localized disease, pulmonary metastases of osteosarcoma occurs in up to 40% of cases and still remain challenging without satisfactory regimen. Apatinib is a oral kinase inhibitor of receptor tyrosine targeting VEGFR2. A pilot study indicated that Apatinib improved the PFS after multi-line chemotherapy failure, and might partly reversed chemo-refractory status for advanced osteosarcoma. Thus, the investigators explored the efficacy of combining Apatinib with current available second-line chemotherapy compared to chemotherapy alone for treating first resectable pulmonary metastases of osteosarcoma following the failure of first-line chemotherapy and wide/radical-margin surgery. Participants will receive 250 mg of apatinib twice daily combined with gemcitabine-docetaxel (GD) regimen before and after the surgical resection of the pulmonary metastases. Osteosarcoma patients with pulmonary recurrence only at baseline will be recruited in the study. The primary end point is progression-free survival rate (PFR) compared with historical control. A12 month PFR of 30% or less is considered inactive, while a 12 month PFR of 50% or greater is regarded as of interest for additional development. With a type I error rate of 5% and a power of 83%, the number of patients needed for this design is 43.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
43
Apatinib 250mg tablet by mouth, bid. 48 hrs break before and 96 hrs after the surgical resection of the pulmonary metastases.
One cycle: gemcitabine 900 mg/m\^2 over 90 min on Day 1, and gemcitabine 900 mg/m\^2 and docetaxel 75 mg/m\^2 on Day 8. Every 21 days were eligible. 1\~2 -week break before and 2-week break after the surgical resection of the pulmonary metastases is taken.
Ruijin Hospital Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, China
12 months Progression-free survival rate(12mPFR)
The proportion of patients with progression-free survival at 12 months according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). A 12mPFR of 30% or less is considered inactive, while a 12mPFR of 50% or greater is regarded as of interest for additional development
Time frame: 12 months from the recruitment of the study
Overall survival (OS)
calculated from the date of treatment start until last follow-up or death, whichever comes first.
Time frame: Baseline until death, followed through study completion, an average of 2 years
Total resectability
The number of patients undergoing pre-planned metastasectomy divided by the number of patients considered resectable at baseline
Time frame: after neoadjuvant systemic therapy, an average of 8~9 weeks
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
The occurrence of each adverse events(AEs), severe AEs(SAEs) and death according the CTCAE\_5.0
Time frame: through study completion, an average of 1 years
Objective response rate (ORR)
Complete Response(CR)+Partial Response(PR) after neoadjuvant systemic therapy
Time frame: after neoadjuvant systemic therapy, an average of 8~9 weeks
Clinical benefit rate (CBR)
CR+PR+stable disease (SD) after neoadjuvant systemic therapy
Time frame: after neoadjuvant systemic therapy, an average of 8~9 weeks
Progression free survival (PFS)
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Progression free survival according to RECIST 1.1
Time frame: Baseline until disease progression or death, whichever occurs first (followed through study completion, an average of 1.5 years)
OS rate
the proportion of OS at 12, 24 months
Time frame: 12 and 24 months from baseline