Paclitaxel Polymeric Micelles and Cisplatin Plus Sintilimab as Neoadjuvant Therapy for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma

Summary

Locally advanced Esophageal Squamous Cell Carcinoma (ESCC) has poor prognosis with standard therapies. Neoadjuvant immunochemotherapy improves pathological response rates, but optimal regimens remain undefined. Paclitaxel polymeric micelles offer enhanced tumor targeting (EPR effect) and reduced toxicity vs. conventional paclitaxel formulations, with no need for premedication. This single-arm, prospective trial evaluates the efficacy and safety of neoadjuvant sintilimab combined with paclitaxel polymeric micelles and cisplatin in resectable locally advanced ESCC.

Timeline

Start

2026-09-01

Primary completion

2027-12-31

Completion

2029-10-01

Publications

• Results Shi M, Gu A, Tu H, Huang C, Wang H, Yu Z, Wang X, Cao L, Shu Y, Wang H, Yang R, Li X, Chang J, Hu Y, Shen P, Hu Y, Guo Z, Tao M, Zhang Y, Liu X, Sun Q, Zhang X, Jiang Z, Zhao J, Chen F, Yu H, Zhang W, Sun J, Li D, Zhou J, Han B, Wu YL. Comparing nanoparticle polymeric micellar paclitaxel and solvent-based paclitaxel as first-line treatment of advanced non-small-cell lung cancer: an open-label, randomized, multicenter, phase III trial. Ann Oncol. 2021 Jan;32(1):85-96. doi: 10.1016/j.annonc.2020.10.479. Epub 2020 Oct 29.
• Results Lu Z, Wang J, Shu Y, Liu L, Kong L, Yang L, Wang B, Sun G, Ji Y, Cao G, Liu H, Cui T, Li N, Qiu W, Li G, Hou X, Luo H, Xue L, Zhang Y, Yue W, Liu Z, Wang X, Gao S, Pan Y, Galais MP, Zaanan A, Ma Z, Li H, Wang Y, Shen L; ORIENT-15 study group. Sintilimab versus placebo in combination with chemotherapy as first line treatment for locally advanced or metastatic oesophageal squamous cell carcinoma (ORIENT-15): multicentre, randomised, double blind, phase 3 trial. BMJ. 2022 Apr 19;377:e068714. doi: 10.1136/bmj-2021-068714.
• Results Lv H, Tian Y, Li J, Huang C, Sun B, Gai C, Li Z, Tian Z. Neoadjuvant Sintilimab Plus Chemotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma. Front Oncol. 2022 Apr 29;12:864533. doi: 10.3389/fonc.2022.864533. eCollection 2022.
• Results Yan X, Duan H, Ni Y, Zhou Y, Wang X, Qi H, Gong L, Liu H, Tian F, Lu Q, Sun J, Yang E, Zhong D, Wang T, Huang L, Wang J, Chaoyang Wang, Wang Y, Wan Z, Lei J, Zhao J, Jiang T. Tislelizumab combined with chemotherapy as neoadjuvant therapy for surgically resectable esophageal cancer: A prospective, single-arm, phase II study (TD-NICE). Int J Surg. 2022 Jul;103:106680. doi: 10.1016/j.ijsu.2022.106680. Epub 2022 May 18.
• Results Zheng Y, Liu XB, Sun HB, Xu J, Shen S, Ba YF, Yan M, Qin Z, Liu BX, Wang ZF, Liu SL, Zhang RX, Chen PN, Liang GH, Yuan D, Li ZX, Liu Q, Wang HR, Li HM, Lv H, Ma X, Zhu J, Yu YK, Xing WQ; written on Henan Cancer Hospital Thoracic Oncology Group (HCHTOG). A phase III study on neoadjuvant chemotherapy versus neoadjuvant toripalimab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: Henan Cancer Hospital Thoracic Oncology Group 1909 (HCHTOG1909). Ann Transl Med. 2021 Jan;9(1):73. doi: 10.21037/atm-20-5404.
• Results Qin J, Xue L, Hao A, Guo X, Jiang T, Ni Y, Liu S, Chen Y, Jiang H, Zhang C, Kang M, Lin J, Li H, Li C, Tian H, Li L, Fu J, Zhang Y, Ma J, Wang X, Fu M, Yang H, Yang Z, Han Y, Chen L, Tan L, Dai T, Liao Y, Zhang W, Li B, Chen Q, Guo S, Qi Y, Wei L, Li Z, Tian Z, Kang X, Zhang R, Li Y, Wang Z, Chen X, Hou Z, Zheng R, Zhu W, He J, Li Y. Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: the randomized phase 3 ESCORT-NEO/NCCES01 trial. Nat Med. 2024 Sep;30(9):2549-2557. doi: 10.1038/s41591-024-03064-w. Epub 2024 Jul 2.
• Results Zhang Z, Hong ZN, Xie S, Lin W, Lin Y, Zhu J, Yang X, Lin Z, Lin J, Kang M. Neoadjuvant sintilimab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: a single-arm, single-center, phase 2 trial (ESONICT-1). Ann Transl Med. 2021 Nov;9(21):1623. doi: 10.21037/atm-21-5381.
• Results He W, Wang C, Li C, Nie X, Li H, Li J, Zhao N, Chen H, Miao X, Han Y, Peng L, Leng X. The efficacy and safety of neoadjuvant immunotherapy in resectable locally advanced esophageal squamous cell carcinoma: A systematic review and meta-analysis. Front Immunol. 2023 Feb 17;14:1118902. doi: 10.3389/fimmu.2023.1118902. eCollection 2023.
• Results Faron M, Cheugoua-Zanetsie M, Tierney J, Thirion P, Nankivell M, Winter K, Yang H, Shapiro J, Vernerey D, Smithers BM, Walsh T, Piessen G, Nilsson M, Boonstra J, Ychou M, Law S, Cunningham D, de Vathaire F, Stahl M, Urba S, Valmasoni M, Williaume D, Thomas J, Lordick F, Tepper J, Roth J, Gebski V, Burmeister B, Paoletti X, van Sandick J, Fu J, Pignon JP, Ducreux M, Michiels S; MANATEC-02 Collaborative Group. Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma. J Clin Oncol. 2023 Oct 1;41(28):4535-4547. doi: 10.1200/JCO.22.02279. Epub 2023 Jul 12.
• Results Kato K, Machida R, Ito Y, Daiko H, Ozawa S, Ogata T, Hara H, Kojima T, Abe T, Bamba T, Watanabe M, Kawakubo H, Shibuya Y, Tsubosa Y, Takegawa N, Kajiwara T, Baba H, Ueno M, Takeuchi H, Nakamura K, Kitagawa Y; JCOG1109 investigators. Doublet chemotherapy, triplet chemotherapy, or doublet chemotherapy combined with radiotherapy as neoadjuvant treatment for locally advanced oesophageal cancer (JCOG1109 NExT): a randomised, controlled, open-label, phase 3 trial. Lancet. 2024 Jul 6;404(10447):55-66. doi: 10.1016/S0140-6736(24)00745-1. Epub 2024 Jun 11.
• Results Tang H, Wang H, Fang Y, Zhu JY, Yin J, Shen YX, Zeng ZC, Jiang DX, Hou YY, Du M, Lian CH, Zhao Q, Jiang HJ, Gong L, Li ZG, Liu J, Xie DY, Li WF, Chen C, Zheng B, Chen KN, Dai L, Liao YD, Li K, Li HC, Zhao NQ, Tan LJ. Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial. Ann Oncol. 2023 Feb;34(2):163-172. doi: 10.1016/j.annonc.2022.10.508. Epub 2022 Nov 15.
• Results Ando N, Kato H, Igaki H, Shinoda M, Ozawa S, Shimizu H, Nakamura T, Yabusaki H, Aoyama N, Kurita A, Ikeda K, Kanda T, Tsujinaka T, Nakamura K, Fukuda H. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol. 2012 Jan;19(1):68-74. doi: 10.1245/s10434-011-2049-9. Epub 2011 Aug 31.
• Results Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Chen Z, Yang H, Wang J, Pang Q, Zheng X, Yang H, Li T, Lordick F, D'Journo XB, Cerfolio RJ, Korst RJ, Novoa NM, Swanson SJ, Brunelli A, Ismail M, Fernando HC, Zhang X, Li Q, Wang G, Chen B, Mao T, Kong M, Guo X, Lin T, Liu M, Fu J; AME Thoracic Surgery Collaborative Group. Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial. J Clin Oncol. 2018 Sep 20;36(27):2796-2803. doi: 10.1200/JCO.2018.79.1483. Epub 2018 Aug 8.
• Results van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. doi: 10.1056/NEJMoa1112088.
• Results Kitagawa Y, Ishihara R, Ishikawa H, Ito Y, Oyama T, Oyama T, Kato K, Kato H, Kawakubo H, Kawachi H, Kuribayashi S, Kono K, Kojima T, Takeuchi H, Tsushima T, Toh Y, Nemoto K, Booka E, Makino T, Matsuda S, Matsubara H, Mano M, Minashi K, Miyazaki T, Muto M, Yamaji T, Yamatsuji T, Yoshida M. Esophageal cancer practice guidelines 2022 edited by the Japan esophageal society: part 1. Esophagus. 2023 Jul;20(3):343-372. doi: 10.1007/s10388-023-00993-2. Epub 2023 Mar 18. No abstract available.
• Results Jiang W, Zhang B, Xu J, Xue L, Wang L. Current status and perspectives of esophageal cancer: a comprehensive review. Cancer Commun (Lond). 2025 Mar;45(3):281-331. doi: 10.1002/cac2.12645. Epub 2024 Dec 26.
• Results Abnet CC, Arnold M, Wei WQ. Epidemiology of Esophageal Squamous Cell Carcinoma. Gastroenterology. 2018 Jan;154(2):360-373. doi: 10.1053/j.gastro.2017.08.023. Epub 2017 Aug 18.
• Results 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.
• Results Uhlenhopp DJ, Then EO, Sunkara T, Gaduputi V. Epidemiology of esophageal cancer: update in global trends, etiology and risk factors. Clin J Gastroenterol. 2020 Dec;13(6):1010-1021. doi: 10.1007/s12328-020-01237-x. Epub 2020 Sep 23.

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Indications