BIOmarker Driven Trial of VEGFR2 Inhibitor in Advanced Sarcoma

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After standard chemotherapy and surgery for the localized disease, pulmonary metastases of bone and soft tissue sarcoma 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. Previous studies ...

After standard chemotherapy and surgery for the localized disease, pulmonary metastases of bone and soft tissue sarcoma 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. Previous studies indicated that Apatinib, as well as other VEGFR inhibitor, showed a preliminary activity with a 4 month progression free rate (PFR) ranging from 40~60% in advanced bone and soft tissue sarcoma after multi-line chemotherapy failure. However, the great inter-individual variability of the agents suggests a lack of predictive biomarker in its clinical use. Furthermore, up to 10~30% of patients may encounter pneumothorax, a potentially life-threatening consequence. Other common debilitating adverse effects (AEs) include surgical wound complication, hand foot skin reaction, etc. 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. Therefore, the investigators aim to explored the efficacy of apatinib monotherapy for advanced bone and soft tissue sarcoma in VEGFR-2 (KDR) 604A>G positive population. We aim to validate our results in both retrospective as well as prospective fashion. First, retrospective data of another 20~25 patients will be analysed for VEGFR2 604A>G polymorphism status as an independent validation. Then, We design a prospective single-arm, open-label, biomarker-driven phase II clinical trial as follows: With all comers(biomarker positive and negative) allowed to be enrolled, only VEGFR-2 (KDR) 604A>G polymorphism positive will be measured for the primary objective. A total of 30 patients with biomarker positive is needed according to the statistical design. The primary objective is to validate the PFR of Apatinib in this population ? 70% at 4 months, against the null hypothesis of PFR ? 50% as in the general sarcoma patients.

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