The aim of this study is to evaluate the efficacy and safety of Apatinib monotherapy for relapsed or refractory advanced bone and soft tissue sarcoma with VEGFR-2 (KDR) 604A>G polymorphism as predictive biomarker
Name: Apatinib monotherapy
Description: The proportion of patients that are progression-free according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Measure: progression free rate (PFR) Time: 4 months from recruitmentDescription: The proportion of patients with negative biomarker that are progression-free according to RECIST 1.1
Measure: progression free rate (PFR) in biomarker negative sub-cohort Time: 4 months from recruitmentDescription: The difference of PFS between biomarker positive and biomarker negative sub-cohorts with log-rank test
Measure: progression free survival(PFS) between biomarker positive and negative sub-cohorts Time: Baseline until disease progression or death, whichever occurs first, assessed for an average of 8 monthsDescription: Correlation of KDR 604 AA,AG,GG genotype with the incidence of pulmonary lesion cavitation or pneumothorax among all comers
Measure: Correlation of KDR polymorphism with pulmonary lesion cavitation/pneumothorax Time: 4 months from recruitmentDescription: Correlation of KDR 604 AA,AG,GG genotype with the incidence of hair depigmentation among all comers
Measure: Correlation of KDR polymorphism with hair depigmentation Time: 4 months from recruitmentDescription: Correlation of KDR 604 AA,AG,GG genotype with progression free survival according to RECIST 1.1 among all comers
Measure: Correlation of KDR polymorphism with progression-free survival(PFS) Time: Baseline until disease progression or death, whichever occurs first, assessed for an average of 8 monthsDescription: The occurrence of each adverse events(AEs), severe AEs(SAEs) and death according the CTCAE_5.0
Measure: Incidence of Treatment-Emergent Adverse Events Time: through study completion, an average of 8 monthsDescription: Correlation of CSF1R (rs10079250) genotype with the incidence of wound complications among all comers
Measure: Correlation of CSF1R polymorphism (rs10079250) with wound complication Time: through study completion, an average of 8 monthsDescription: Correlation of PDGFRα (rs35597368) genotype with the incidence of hand foot skin reaction among all comers
Measure: Correlation of PDGFRα polymorphism (rs35597368) with hand foot skin reaction Time: through study completion, an average of 8 monthsDescription: to correlate the incidence of targeted therapy related AEs (pulmonary lesion cavitation, pneumothorax, hair depigmentation) with the PFS
Measure: Early identification of AEs as predictive biomarker Time: Baseline until disease progression or death, whichever occurs first, assessed for an average of 8 monthsDescription: The PFS for each subgroups in terms of clinicopathological characteristics (age, gender, histological type, solitary or multiple metastases, unilateral or bilateral metastases, early or late metastases, calcifying or non-calcifying lesions, with or without lesion cavitation, with or without AEs [especially pneumothorax, hand-foot skin reactions, hair depigmentation], etc
Measure: Exploratory outcome: Subgroup analysis of progression-free survival(PFS) Time: Baseline until disease progression or death, whichever occurs first, assessed for an average of 8 monthsDescription: To explore the molecular basis underlying the difference of biomarker positive and negative sub-cohorts using next generation sequencing
Measure: Exploratory outcome: the molecular analysis of tumor sample Time: through study completion, an average of 8 monthsDescription: to compare the growth pattern/ distribution of pulmonary versus extrapulmonary lesion at baseline and at disease progression between the two sub-cohorts
Measure: Exploratory outcome: the pattern of disease progression between the sub-cohorts Time: Baseline until disease progression or death, whichever occurs first, assessed for an average of 8 monthsDescription: to compare the diagnostic value of the 1.0 mm versus 5.0 mm CT scan for the radiological evaluation of small lung nodule as tumor recurrence
Measure: Exploratory outcome: 1.0-mm CT scan for pulmonary assessment Time: Baseline until disease progression or death, whichever occurs first, assessed for an average of 8 monthsAllocation: N/A
Single Group Assignment
There are 3 SNPs
Correlation of CSF1R polymorphism (rs10079250) with wound complication.
Correlation of CSF1R (rs10079250) genotype with the incidence of wound complications among all comers.
Our preliminary data suggests that rs2071559_VEGFR2 604A>G polymorphism is associated pulmonary tumor cavitation (predisposes one to pneumothorax), hair depigmentation, superior efficacy and less likelihood of extra-pulmonary lesion.
Correlation of PDGFRα polymorphism (rs35597368) with hand foot skin reaction.
Correlation of PDGFRα (rs35597368) genotype with the incidence of hand foot skin reaction among all comers.