OncoTargets and Therapy (Sep 2021)

Study on Efficacy and Safety of Low-Dose Apatinib Combined with Camrelizumab and SOX Regimen as First-Line Treatment of Locally Advanced and Unresectable Gastric/Gastroesophageal Junction Cancer: A Protocol for an Open-Label, Dose Escalation and Extension Phase Ib Clinical Trial

  • Wang KX,
  • Cui TY,
  • Yang XD,
  • Wang GQ,
  • Jiang QS,
  • Sun H,
  • Jiang NY,
  • Yong XM,
  • Shi CB,
  • Ding YB,
  • Chen XF,
  • Fang YY

Journal volume & issue
Vol. Volume 14
pp. 4859 – 4865

Abstract

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Kang-Xin Wang,1,* Ting-Yun Cui,1,* Xu-Dong Yang,2 Guo-Qun Wang,1 Qiu-Sheng Jiang,2 Hui Sun,1 Nan-Yuan Jiang,1 Xiao-Min Yong,3 Chuan-Bing Shi,4 Yong-Bin Ding,2 Xiao-Feng Chen,1,5,* Yue-Yu Fang1,* 1Department of Oncology, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China; 2Department of General Surgery, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China; 3Department of Radiology, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China; 4Department of Pathology, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), Nanjing, 211800, People’s Republic of China; 5Department of Oncology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yue-Yu FangDepartment of Oncology, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), No. 166 Shanghe Street, Pukou District, Nanjing, 211800, People’s Republic of ChinaEmail [email protected] ChenDepartment of Oncology, The First Affiliated Hospital with Nanjing Medical University, Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital), No. 300 Guangzhou Road, Nanjing, 210029, People’s Republic of ChinaEmail [email protected]: The standard treatment for advanced gastric/gastroesophageal junction cancer (AGC/GEJC) is palliative chemotherapy combined with targeted therapy. The SOX regimen (S-1 plus oxaliplatin) is recommended as neoadjuvant or palliative first-line chemotherapy in Asian patients. Apatinib, an oral VEGFR tyrosine kinase inhibitor, is associated with additional survival benefit as third- or subsequent-line therapy. However, the median overall survival time of AGC/GEJC is only 8– 11 months in the West and 13– 17 months in East Asia/Japan, even with the application of anti-angiogenic agents. Hence, the multimodal and individual management of patients is challenging standards to improve prognosis, including the preferential use of low-dose anti-angiogenic drugs and immunotherapy, as well as the application of multi-disciplinary treatment (MDT)-directed conversion therapy.Methods/Design: This single-center study was designed to combine low-dose apatinib with camrelizumab plus the SOX regimen in diagnosed potentially resectable and initially unresectable AGC/GEJC. This a prospective, open-label, single-arm, dose escalation and extension phase Ib clinical trial, conducted in Jiangsu Province Hospital, beginning from June 2020. All patients will first receive this combined regimen (3 weeks/cycle) for at most eight cycles, then apatinib and camrelizumab in maintenance therapy until disease progression, intolerable toxicity, death, a maximum 2 years of treatment or discontinuation for any reason. Follow-up and evaluation will be carried out regularly. If surgery is allowed by MDT discussions, oral apatinib will be discontinued during the last preoperative cycle. The primary endpoints are the objective response rate and maximum tolerated dose according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) and the Common Terminology Criteria for Adverse Events (CTCAE) criteria (version 5.0).Discussion: This study will assess the response and side effects of AGC/GEJC patients in the use of low-dose apatinib combined with camrelizumab and the SOX regimen, and this combined therapy is expected to be a feasible and optimized first-line treatment option. In addition, this study will provide robust evidence and novel ideas for conversion therapy.Trial Registration: ChiCTR.gov.cn: ChiCTR2000034109.Keywords: clinical trial, AGC/GEJC, low-dose apatinib, camrelizumab, SOX regimen, protocol

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