1734TiP - Pulmonary resectable metastases of osteosarcoma with apatinib and chemotherapy (PROACH): A multi-center phase II randomized clinical trial

Abstract

BackgroundThe prognosis of osteosarcoma at its metastatic stage remains unchanged over the last several decades. Although 60∼80% first pulmonary recurrences were reportedly to be resectable, it’s surprising that the vast majority of trials to date were designed for metastatic osteosarcoma that were considered inoperable. Apatinib, a VEGFR2 inhibitor, is marked by its superior overall response rate (ORR) of ∼55% compared with other anti-angiogenic agents. Therefore, we aim to assess the efficacy and safety of incorporating apatinib with second-line chemotherapy preoperatively for resectable pulmonary metastatic osteosarcoma, with the intent to shrink the lesions for easier resection and eradicate the micro-metastatic residue using the combination therapy. Trial designThis study is a multicenter, open-label, randomized phase II trial (ClinicalTrials ID: NCT03742193) in which ∼180 participants were to be randomized to an active control arm and an intervention arm in 1:1 ratio. Patients in the intervention arm will receive 250mg apatinib twice daily combined with gemcitabine-docetaxel (GD) regimen before and after the pulmonary metastasectomy, while the control arm will receive gemcitabine-docetaxel (GD) regimen only. Osteosarcoma patients with pulmonary recurrence only, which are potentially resectable at baseline will be recruited in the trial. The primary endpoint is progression-free survival (PFS) and the pre-specified target is an at least 30% decrease of hazard rate of progression in the experimental arm compared with the control arm. Error rate level of the trial was set at an one-sided α value of 0.1 and a power (1-β value) of 0.8, with mid-term assessment for both early efficacy and futility. Secondary objectives are to analyze the effect of the new regimen on overall survival, total resectability, objective response rate, clinical benefit rate, tolerability, as well as the potential predictive biomarker(s). Clinical trial identificationNCT03742193; release date: March 2018. Legal entity responsible for the studyAn IIT trial by Ruijin Hospital, Orthopaedic oncology group. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.