Surufatinib in Combination With Neoadjuvant Chemo-immunotherapy and Concurrent Chemoradiotherapy for Patients With Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma

Summary

The combination of surufatinib with neoadjuvant chemo-immunotherapy and definitive concurrent chemoradiotherapy represents a promising new therapeutic strategy that may further improve the prognosis of patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC). Therefore, we propose to conduct a prospective, single-arm, phase II clinical trial to evaluate the efficacy and safety of this regimen in patients with unresectable, locally advanced ESCC.

Timeline

Start

2025-07-20

Primary completion

2029-07-19

Completion

2029-07-19

Publications

• Background Zhang P, Chen Z, Shi S, Li Z, Ye F, Song L, Zhang Y, Yin F, Zhang X, Xu J, Cheng Y, Su W, Shi M, Fan S, Tan P, Zhong C, Lu M, Shen L. Efficacy and safety of surufatinib plus toripalimab, a chemotherapy-free regimen, in patients with advanced gastric/gastroesophageal junction adenocarcinoma, esophageal squamous cell carcinoma, or biliary tract cancer. Cancer Immunol Immunother. 2024 May 7;73(7):119. doi: 10.1007/s00262-024-03677-7.
• Background Xu J, Shen L, Zhou Z, Li J, Bai C, Chi Y, Li Z, Xu N, Li E, Liu T, Bai Y, Yuan Y, Li X, Wang X, Chen J, Ying J, Yu X, Qin S, Yuan X, Zhang T, Deng Y, Xiu D, Cheng Y, Tao M, Jia R, Wang W, Li J, Fan S, Peng M, Su W. Surufatinib in advanced extrapancreatic neuroendocrine tumours (SANET-ep): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Nov;21(11):1500-1512. doi: 10.1016/S1470-2045(20)30496-4. Epub 2020 Sep 20.
• Background Xu J, Shen L, Bai C, Wang W, Li J, Yu X, Li Z, Li E, Yuan X, Chi Y, Yin Y, Lou W, Xu N, Bai Y, Zhang T, Xiu D, Wang X, Yuan Y, Chen J, Qin S, Jia R, Lu M, Cheng Y, Zhou Z, Li J, He J, Su W. Surufatinib in advanced pancreatic neuroendocrine tumours (SANET-p): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Nov;21(11):1489-1499. doi: 10.1016/S1470-2045(20)30493-9. Epub 2020 Sep 20.
• Background Syed YY. Surufatinib: First Approval. Drugs. 2021 Apr;81(6):727-732. doi: 10.1007/s40265-021-01489-y.
• Background Wang J, Yu JP, Wang JL, Ni XC, Sun ZQ, Sun W, Nie B, Jiang JT, Sun SP, Wu CP. [Pathologic response and changes of serum VEGF during chemoradiotherapy may predict prognosis in non-surgical patients with esophageal carcinoma]. Zhonghua Zhong Liu Za Zhi. 2016 Aug;38(8):589-95. doi: 10.3760/cma.j.issn.0253-3766.2016.08.005. Chinese.
• Background Zhu Y, Wen J, Li Q, Chen B, Zhao L, Liu S, Yang Y, Wang S, Lv Y, Li J, Zhang L, Hu Y, Liu M, Xi M. Toripalimab combined with definitive chemoradiotherapy in locally advanced oesophageal squamous cell carcinoma (EC-CRT-001): a single-arm, phase 2 trial. Lancet Oncol. 2023 Apr;24(4):371-382. doi: 10.1016/S1470-2045(23)00060-8.
• Background Shinoda M, Ando N, Kato K, Ishikura S, Kato H, Tsubosa Y, Minashi K, Okabe H, Kimura Y, Kawano T, Kosugi S, Toh Y, Nakamura K, Fukuda H; Japan Clinical Oncology Group. Randomized study of low-dose versus standard-dose chemoradiotherapy for unresectable esophageal squamous cell carcinoma (JCOG0303). Cancer Sci. 2015 Apr;106(4):407-12. doi: 10.1111/cas.12622. Epub 2015 Mar 9.
• Background Suntharalingam M, Winter K, Ilson D, Dicker AP, Kachnic L, Konski A, Chakravarthy AB, Anker CJ, Thakrar H, Horiba N, Dubey A, Greenberger JS, Raben A, Giguere J, Roof K, Videtic G, Pollock J, Safran H, Crane CH. Effect of the Addition of Cetuximab to Paclitaxel, Cisplatin, and Radiation Therapy for Patients With Esophageal Cancer: The NRG Oncology RTOG 0436 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2017 Nov 1;3(11):1520-1528. doi: 10.1001/jamaoncol.2017.1598.
• Background Hulshof MCCM, Geijsen ED, Rozema T, Oppedijk V, Buijsen J, Neelis KJ, Nuyttens JJME, van der Sangen MJC, Jeene PM, Reinders JG, van Berge Henegouwen MI, Thano A, van Hooft JE, van Laarhoven HWM, van der Gaast A. Randomized Study on Dose Escalation in Definitive Chemoradiation for Patients With Locally Advanced Esophageal Cancer (ARTDECO Study). J Clin Oncol. 2021 Sep 1;39(25):2816-2824. doi: 10.1200/JCO.20.03697. Epub 2021 Jun 8.
• Background Conroy T, Galais MP, Raoul JL, Bouche O, Gourgou-Bourgade S, Douillard JY, Etienne PL, Boige V, Martel-Lafay I, Michel P, Llacer-Moscardo C, Francois E, Crehange G, Abdelghani MB, Juzyna B, Bedenne L, Adenis A; Federation Francophone de Cancerologie Digestive and UNICANCER-GI Group. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014 Mar;15(3):305-14. doi: 10.1016/S1470-2045(14)70028-2. Epub 2014 Feb 18.
• Background Xu Y, Dong B, Zhu W, Li J, Huang R, Sun Z, Yang X, Liu L, He H, Liao Z, Guan N, Kong Y, Wang W, Chen J, He H, Qiu G, Zeng M, Pu J, Hu W, Bao Y, Liu Z, Ma J, Jiang H, Du X, Hu J, Zhuang T, Cai J, Huang J, Tao H, Liu Y, Liang X, Zhou J, Tao G, Zheng X, Chen M. A Phase III Multicenter Randomized Clinical Trial of 60 Gy versus 50 Gy Radiation Dose in Concurrent Chemoradiotherapy for Inoperable Esophageal Squamous Cell Carcinoma. Clin Cancer Res. 2022 May 2;28(9):1792-1799. doi: 10.1158/1078-0432.CCR-21-3843.
• Background Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, Okawara G, Rosenthal SA, Kelsen DP. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002 Mar 1;20(5):1167-74. doi: 10.1200/JCO.2002.20.5.1167.
• Background Cooper JS, Guo MD, Herskovic A, Macdonald JS, Martenson JA Jr, Al-Sarraf M, Byhardt R, Russell AH, Beitler JJ, Spencer S, Asbell SO, Graham MV, Leichman LL. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA. 1999 May 5;281(17):1623-7. doi: 10.1001/jama.281.17.1623.
• Background Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

Drugs

Indications