A Multicenter Trial of YSQTG vs. Simulated Agents With Neoadjuvant Chemoradiotherapy or Chemoimmunotherapy for EC

Summary

Esophageal cancer is a high - incidence cancer type in China, characterized by high incidence, high mortality, and low survival rates. Over 90% of esophageal cancer cases in China are squamous cell carcinoma, while in Western countries, approximately 80% are adenocarcinomas. Current international guidelines, including those of the NCCN and CSCO, are not entirely suitable for the diagnosis and treatment of esophageal cancer in the Chinese context. In recent years, although the 5 - year survival rate for esophageal cancer has improved, significant challenges remain, such as severe side effects during chemoradiotherapy and targeted - immunotherapy, decreased patient tolerance and quality of life, and even interruption of treatment. To leverage the synergistic role of traditional Chinese medicine (TCM) in the treatment of major diseases, this study, which builds on previous research, is founded on the theory of "reinforcing healthy qi to strengthen the body, removing toxins, and resolving stasis." It aims to conduct a multicenter, randomized, controlled clinical trial of the TCM formula Yishen Qutong Granules, designed to reinforce healthy qi to strengthen the body and remove toxins, in combination with neoadjuvant concurrent therapy for locally advanced esophageal squamous cell carcinoma. The study will enroll 268 patients (1:1 ratio) with locally advanced esophageal squamous cell carcinoma (cTNM stage III - IVa) who are expected to undergo neoadjuvant concurrent therapy and are potentially resectable. On the basis of conventional Western medical treatment, the treatment group will be administered the patented TCM formula Yishen Qutong Granules orally, while the control group will receive a Yishen Qutong Simulated Granules orally. The primary outcome measure will be the clinical benefit rate (CBR, CBR = CR + PR + SD), with secondary outcomes including pathological response rate (mPR), R0 resection rate, and TCM syndrome symptom score. The study aims to establish an objective evaluation system for the efficacy and safety of combined treatment based on the integration of disease and syndrome differentiation. It will also elucidate the mechanisms underlying the therapeutic effects of Yishen Qutong Granules.

Timeline

Start

2024-08-22

Primary completion

2025-10-31

Completion

2027-10-31

Publications

• Background Deboever N, Jones CM, Yamashita K, Ajani JA, Hofstetter WL. Advances in diagnosis and management of cancer of the esophagus. BMJ. 2024 Jun 3;385:e074962. doi: 10.1136/bmj-2023-074962.
• Background DaSilva LL, Aguiar PN Jr, de Lima Lopes G. Immunotherapy for Advanced Esophageal Squamous Cell Carcinoma-Renewed Enthusiasm and a Lingering Challenge. JAMA Oncol. 2021 Nov 1;7(11):1613-1614. doi: 10.1001/jamaoncol.2021.4410. No abstract available.
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• Background The Lancet. GLOBOCAN 2018: counting the toll of cancer. Lancet. 2018 Sep 22;392(10152):985. doi: 10.1016/S0140-6736(18)32252-9. Epub 2018 Sep 20. No abstract available.
• Background Conway E, Wu H, Tian L. Overview of Risk Factors for Esophageal Squamous Cell Carcinoma in China. Cancers (Basel). 2023 Nov 27;15(23):5604. doi: 10.3390/cancers15235604.
• Background Morgan E, Soerjomataram I, Rumgay H, Coleman HG, Thrift AP, Vignat J, Laversanne M, Ferlay J, Arnold M. The Global Landscape of Esophageal Squamous Cell Carcinoma and Esophageal Adenocarcinoma Incidence and Mortality in 2020 and Projections to 2040: New Estimates From GLOBOCAN 2020. Gastroenterology. 2022 Sep;163(3):649-658.e2. doi: 10.1053/j.gastro.2022.05.054. Epub 2022 Jun 4.
• Background Liu J, Yang Y, Liu Z, Fu X, Cai X, Li H, Zhu L, Shen Y, Zhang H, Sun Y, Chen H, Yu B, Zhang R, Shao J, Zhang M, Li Z. Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma. J Immunother Cancer. 2022 Mar;10(3):e004291. doi: 10.1136/jitc-2021-004291.
• Background 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.
• Background Luo H, Lu J, Bai Y, Mao T, Wang J, Fan Q, Zhang Y, Zhao K, Chen Z, Gao S, Li J, Fu Z, Gu K, Liu Z, Wu L, Zhang X, Feng J, Niu Z, Ba Y, Zhang H, Liu Y, Zhang L, Min X, Huang J, Cheng Y, Wang D, Shen Y, Yang Q, Zou J, Xu RH; ESCORT-1st Investigators. Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial. JAMA. 2021 Sep 14;326(10):916-925. doi: 10.1001/jama.2021.12836.
• Background 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, Zhang X, Li Q, Wang G, Chen B, Mao T, Kong M, Guo X, Lin T, Liu M, Fu J. Long-term Efficacy of Neoadjuvant Chemoradiotherapy Plus Surgery for the Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma: The NEOCRTEC5010 Randomized Clinical Trial. JAMA Surg. 2021 Aug 1;156(8):721-729. doi: 10.1001/jamasurg.2021.2373.
• Background Wang ZX, Cui C, Yao J, Zhang Y, Li M, Feng J, Yang S, Fan Y, Shi J, Zhang X, Shen L, Shu Y, Wang C, Dai T, Mao T, Chen L, Guo Z, Liu B, Pan H, Cang S, Jiang Y, Wang J, Ye M, Chen Z, Jiang D, Lin Q, Ren W, Wang J, Wu L, Xu Y, Miao Z, Sun M, Xie C, Liu Y, Wang Q, Zhao L, Li Q, Huang C, Jiang K, Yang K, Li D, Liu Y, Zhu Z, Chen R, Jia L, Li W, Liao W, Liu HX, Ma D, Ma J, Qin Y, Shi Z, Wei Q, Xiao K, Zhang Y, Zhang Y, Chen X, Dai G, He J, Li J, Li G, Liu Y, Liu Z, Yuan X, Zhang J, Fu Z, He Y, Ju F, Liu Z, Tang P, Wang T, Wang W, Zhang J, Luo X, Tang X, May R, Feng H, Yao S, Keegan P, Xu RH, Wang F. Toripalimab plus chemotherapy in treatment-naive, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial. Cancer Cell. 2022 Mar 14;40(3):277-288.e3. doi: 10.1016/j.ccell.2022.02.007. Epub 2022 Mar 3.
• Background Obermannova R, Alsina M, Cervantes A, Leong T, Lordick F, Nilsson M, van Grieken NCT, Vogel A, Smyth EC; ESMO Guidelines Committee. Electronic address: [email protected]. Oesophageal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022 Oct;33(10):992-1004. doi: 10.1016/j.annonc.2022.07.003. Epub 2022 Jul 29. No abstract available.
• Background Ajani JA, D'Amico TA, Bentrem DJ, Cooke D, Corvera C, Das P, Enzinger PC, Enzler T, Farjah F, Gerdes H, Gibson M, Grierson P, Hofstetter WL, Ilson DH, Jalal S, Keswani RN, Kim S, Kleinberg LR, Klempner S, Lacy J, Licciardi F, Ly QP, Matkowskyj KA, McNamara M, Miller A, Mukherjee S, Mulcahy MF, Outlaw D, Perry KA, Pimiento J, Poultsides GA, Reznik S, Roses RE, Strong VE, Su S, Wang HL, Wiesner G, Willett CG, Yakoub D, Yoon H, McMillian NR, Pluchino LA. Esophageal and Esophagogastric Junction Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2023 Apr;21(4):393-422. doi: 10.6004/jnccn.2023.0019.
• Background Yang H, Wang F, Hallemeier CL, Lerut T, Fu J. Oesophageal cancer. Lancet. 2024 Nov 16;404(10466):1991-2005. doi: 10.1016/S0140-6736(24)02226-8.
• Background Qi L, Wang J, Hou S, Liu S, Zhang Q, Zhu S, Liu S, Zhang S. Unraveling the tumor microenvironment of esophageal squamous cell carcinoma through single-cell sequencing: A comprehensive review. Biochim Biophys Acta Rev Cancer. 2025 Feb;1880(1):189264. doi: 10.1016/j.bbcan.2025.189264. Epub 2025 Jan 11.

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