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Sintilimab plus bevacizumab and CapeOx (BBCAPX) on first-line treatment in patients with RAS mutant, microsatellite stable, metastatic colorectal cancer: study protocol of a randomized, open-label, multicentric study.
Fang, Xuefeng; Zhong, Chenhan; Weng, Shanshan; Hu, Hanguang; Wang, Jian; Xiao, Qian; Wang, Jianwei; Sun, Lifeng; Xu, Dong; Liao, Xiujun; Dong, Caixia; Zhang, Suzhan; Li, Jun; Ding, Kefeng; Yuan, Ying.
Afiliación
  • Fang X; Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.
  • Zhong C; Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.
  • Weng S; Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.
  • Hu H; Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.
  • Wang J; Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.
  • Xiao Q; Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.
  • Wang J; Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.
  • Sun L; Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.
  • Xu D; Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.
  • Liao X; Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.
  • Dong C; Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.
  • Zhang S; Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.
  • Li J; Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China. 2307016@zju.edu.cn.
  • Ding K; Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China. dingkefeng@zju.edu.cn.
  • Yuan Y; Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China. dingkefeng@zju.edu.cn.
BMC Cancer ; 23(1): 676, 2023 Jul 18.
Article en En | MEDLINE | ID: mdl-37464378
BACKGROUND: Rat sarcoma viral oncogene homolog (RAS) gene mutation is a common molecular event in colorectal cancer (CRC). The prognosis of mCRC (metastatic colorectal cancer) patients with RAS mutation is poor and capecitabine and oxaliplatin (CapeOx) plus bevacizumab has shown to be one of the standard therapeutic regimens as first line for these patients with objective response rate (ORR) of ~ 50% and median progression-free survival (mPFS) of 8-9 months. Immunotherapy, especially anti-programmed death 1 (PD-1) monoclonal antibody has demonstrated ground-breaking results in deficient mismatch repair (dMMR) / microsatellite instability-high (MSI-H) mCRC patients. However, the response rate of in microsatellite stable (MSS) patients is extremely low. In addition, preclinical studies have demonstrated that anti-Vascular endothelial growth factor (VEGF) agents, such as bevacizumab, can induce tumor vascular normalization and enhance antitumor immunity. Previous study indicated the combination of chemotherapy, anti-VEGF agents (bevacizumab) with immune checkpoint inhibitors may have promising clinical activity in RAS mutant, MSS refractory mCRC patients. Based on these evidences, we will explore the combination of CapeOx with bevacizumab and sintilimab (anti-PD-1 monoclonal antibody) in RAS mutant, MSS mCRC patients as first-line therapy. METHODS: This is a randomized, open-label, multicentric clinical trial. In the sintilimab arm, patients will receive sintilimab in combination with CapeOx and bevacizumab. In the control arm, patients will receive CapeOx and bevacizumab. This trial will recruit 494 patients from 20 centers and randomly (1:1) disseminated into two groups. The primary endpoint is the PFS. The secondary endpoints include overall survival, safety, ORR, and disease control rate. DISCUSSION: This study may provide new ideas for optimizing oncology treatment planning for RAS mutant, MSS mCRC patients in the first-line set. TRIAL REGISTRATION: This study is short for BBCAPX and has been registered at clinicaltrials.gov registry with identifier NCT05171660.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias del Recto / Neoplasias Colorrectales / Neoplasias del Colon Tipo de estudio: Clinical_trials / Guideline / Prognostic_studies Límite: Humans Idioma: En Revista: BMC Cancer Asunto de la revista: NEOPLASIAS Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias del Recto / Neoplasias Colorrectales / Neoplasias del Colon Tipo de estudio: Clinical_trials / Guideline / Prognostic_studies Límite: Humans Idioma: En Revista: BMC Cancer Asunto de la revista: NEOPLASIAS Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido