Pulmonary Resectable Metastases of Osteosarcoma With Anti-angiogenics and CHemotherapy
- Conditions
- Pulmonary MetastasesApatinibOsteosarcoma
- Interventions
- Drug: GD regimen
- Registration Number
- NCT03742193
- Lead Sponsor
- Ruijin Hospital
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 43
- age between 10 and 50 years;
- diagnosis of histologically confirmed high grade osteosarcoma;
- identification of pulmonary metastases without the existence of local recurrence(previous re-resection of local recurrence with wide margin is allowed).
- resectable pulmonary nodule(s), defined as nodule(s) that are removable by wedge resection/ segmentectomy/lobectomy without necessitating a pneumonectomy (e.g., nodules immediately adjacent to the main stem bronchus or main pulmonary vessels)
- prior treatment consisted of standard National Comprehensive Cancer Network (NCCN) guideline recommended first-line chemotherapy
- wide/radical-margin surgical resection of the primary tumor completed at least 4 weeks before enrollment.
- Eastern Cooperative Oncology Group(ECOG) performance status 0-2 with a life expectancy >3 months;
- adequate renal, hepatic, and hemopoietic function;
- normal or controlled blood pressure;
- no thoracic comorbidities with adequate pulmonary function eligible for thoracic surgery
- previously exposed to GD chemotherapy or VEGFR2 Tyrosine-kinase inhibitors (TKIs);
- existence of local recurrence;
- have had other kinds of malignant tumors at the same time;
- cardiac insufficiency or arrhythmia;
- uncontrolled complications, such as diabetes mellitus and so on;
- coagulation disorders or Hemorrhagic diseases ;
- metastases considered unresectable or borderline resectable at baseline
- intolerable of thoracis surgery
- pleural or peritoneal effusion that needs to be handled by surgical treatment;
- combined with other infections or wounds
- wound dystrophy, poor soft-tissue around implantation or other wound complications risky of non-healing given angiogenesis inhibitor assessed by the investigators
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Apatinib + GD group Apatinib Apatinib + GD regimen. For unilateral metastases,3 cycles before metastasectomy, and 4 cycles after. For bilateral metastases, 3 cycles before first metastasectomy, 1 cycle inbetween, and then second metastasectomy followed by 4 cycles. Apatinib monotherapy is then maintained until 1 year following complete resection. Apatinib + GD group GD regimen Apatinib + GD regimen. For unilateral metastases,3 cycles before metastasectomy, and 4 cycles after. For bilateral metastases, 3 cycles before first metastasectomy, 1 cycle inbetween, and then second metastasectomy followed by 4 cycles. Apatinib monotherapy is then maintained until 1 year following complete resection.
- Primary Outcome Measures
Name Time Method 12 months Progression-free survival rate(12mPFR) 12 months from the recruitment of the study 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
- Secondary Outcome Measures
Name Time Method Overall survival (OS) Baseline until death, followed through study completion, an average of 2 years calculated from the date of treatment start until last follow-up or death, whichever comes first.
Total resectability after neoadjuvant systemic therapy, an average of 8~9 weeks The number of patients undergoing pre-planned metastasectomy divided by the number of patients considered resectable at baseline
Progression free survival (PFS) Baseline until disease progression or death, whichever occurs first (followed through study completion, an average of 1.5 years) Progression free survival according to RECIST 1.1
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] through study completion, an average of 1 years The occurrence of each adverse events(AEs), severe AEs(SAEs) and death according the CTCAE_5.0
Objective response rate (ORR) after neoadjuvant systemic therapy, an average of 8~9 weeks Complete Response(CR)+Partial Response(PR) after neoadjuvant systemic therapy
Clinical benefit rate (CBR) after neoadjuvant systemic therapy, an average of 8~9 weeks CR+PR+stable disease (SD) after neoadjuvant systemic therapy
OS rate 12 and 24 months from baseline the proportion of OS at 12, 24 months
Trial Locations
- Locations (1)
Ruijin Hospital Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, Shanghai, China