Efficacy and Safety of Concurrent PD-1 Inhibitor and Radiotherapy With Immunonutrition for Esophageal Squamous Cell Carcinoma

NCT06342167 | Active Not Recruiting Phase 2

• 1 other identifier: NCC4409
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 9

Brief Summary

At present, concurrent chemoradiotherapy (cCRT) with platin-based dual-drug regimen is the standard treatment for inoperable, locally advanced esophageal cancer in patients with a good performance status. However, cCRT has substantial toxic effects, and a large number of patients with older age, malnutrition and other morbidities, cannot tolerate cCRT. Several phase II trials showed combining PD-1 inhibitor with definitive cCRT provided encouraging activity and acceptable toxicity in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). Therefore, this single-arm, multicenter, phase II trial aims to assess the efficacy and safety of immunotherapy plus radiotherapy with immunonutrition support in patients with LA-ESCC and positive PD-L1 expression who are intolerant to cCRT.

Conditions

Locally Advanced Esophageal Squamous Cell Carcinoma; Sintilimab; Radiotherapy; Concurrent Chemoradiotherapy; Immunonutrition

Outcome Measures

Primary Outcomes (1)

• 1-year Progression-free survival rate (PFS)

  Progression-free survival rate is defined the rate of progress event at 1-years after radiotherapy. Progression event is defined as event of primary tumor and regional recurrence, or distant metastasis

  From start of treatment until 1 years of follow-up.

Secondary Outcomes (5)

• Objective response rate

  Measured at 3 months after completion of radiotherapy

• Progression-free survival

  Measured at months 6, 12, 18, and 24.

• Overall survival rate

  Measured at months 6, 12, 18, and 24.

• Overall survival

  From start of treatment until 3 years of follow-up.

• Incidence of adverse events

  Measured at months 6, 12, 18, and 24.

Study Arms (1)

Concurrent immunotherapy and radiotherapy

EXPERIMENTAL

Sintilimab + radiotherapy + enteral nutritional emulsion (TPF-T)

Radiation: Radiotherapy; Drug: Programmed Cell Death Protein 1 Inhibitor; Dietary Supplement: Immunonutrition support

Interventions

Radiotherapy RADIATION

Interventions consist of 50-60 Gy in 25-30 fractions of radiotherapy.

Concurrent immunotherapy and radiotherapy

Programmed Cell Death Protein 1 Inhibitor DRUG

200 mg of Sintilimab administered every three weeks concurrently with radiotherapy and after radiotherapy as consolidation therapy up to 1year.

Also known as: PD-1 Inhibitor

Concurrent immunotherapy and radiotherapy

Immunonutrition support DIETARY_SUPPLEMENT

600-1600 ml of TPF-T per day according to the nutrition status evaluation

Also known as: enteral nutritional emulsion

Concurrent immunotherapy and radiotherapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years or order.
• Diagnosed with locally advanced or early stage esophageal squamous cell carcinoma by pathological examinations of the primary lesion and imaging examinations, which are not resectable.
• Confirmed to be unresectable and unable to tolerate synchronous chemoradiotherapy by multidisciplinary consultation, and has not undergone systemic drug therapy in the past.
• PD-L1 tumor proportion score or combined positive score of ≥1%.
• At least one measurable lesion on imaging according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 -2.
• Expected survival time of more than three months.
• Adequate organ function defined as the following laboratory indicators:
• Absolute neutrophil count (ANC) ≥ 1.5×109/L without use of granulocyte colony-stimulating factor in the past 14 days.
• Platelet count ≥ 100×109/L without blood transfusion in the past 14 days.
• Hemoglobin \> 9g/dL without blood transfusion or use of erythropoietin-stimulating agents in the past 14 days.
• Total bilirubin ≤ 1.5×upper limit of normal (ULN).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5×ULN.
• Creatinine ≤ 1.5×ULN and creatinine clearance calculated using the Cockcroft-Gault formula) ≥ 60 ml/min.
• Good coagulation function, defined as an international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5×ULN.

You may not qualify if:

• Subjects with any of the following conditions cannot participate in the study:
• A high risk of bleeding or perforation due to clear invasion of adjacent organs (large arteries or trachea) by the tumor, or with fistula.
• Diagnosed with malignancies other than esophageal cancer within 3 years prior to the first dose (excluding cured basal cell carcinoma or squamous cell carcinoma of the skin and/or radically resected carcinoma in situ).
• Previous immunological or immunomodulatory drugs as systemic whole-body treatment, including thymic peptides, interferon, interleukins, except for local use to control pleural effusion.
• Previous chest radiotherapy.
• A history of allogeneic organ transplantation (except for corneal transplantation) or allogeneic hematopoietic stem cell transplantation.
• Allergic to the study drug, Sintilimab, or its excipients.
• A history of human immunodeficiency virus (HIV) infection (i.e., HIV1/2 antibody positive).
• Untreated active hepatitis B defined as HBsAg positive and HBV-DNA copy number greater than the upper limit of the normal value in the laboratory of the study center.
• Note: Patients with hepatitis B who meet the following criteria can also be included:
• HBV viral load \<1000 copies/ml (200IU/ml) before the first dose; the patient should receive anti-HBV treatment throughout chemotherapy in the entire study to avoid viral reactivation.
• For patients who are anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load (-), no prophylactic anti-HBV treatment is required, but close monitoring of viral reactivation is needed.
• Active hepatitis C virus (HCV) infection defined as HCV antibody positive and HCV-RNA levels higher than the detection limit.
• Having received live vaccines within 30 days prior to the first dose (Cycle 1, Day 1).
• Note: It is allowed to receive inactivated virus vaccines for seasonal influenza within 30 days prior to the first dose, but attenuated live influenza vaccines administered intranasally are not allowed.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (9)

Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Beijing, Beijing Municipality, 100021, China

Location

Department of Radiation Oncology，Clinical Oncology School of Fujian Medical University，Fujian Cancer Hospital

Fujian, Fujian, China

Location

Department of Oncology, Affiliated Hospital, Hebei University of Engineering

Handan, Hebei, China

Location

Department 1st of Radiation Oncology, Anyang Tumor Hospital

Anyang, Henan, China

Location

Department of Radiation Oncology the first affiliated hospital of Xinxiang Medical University

Xinxiang, Henan, China

Location

Department of Radiation Oncology, General Hospital of Ningxia Medical University

Yinchuan, Ningxia, China

Location

Department of Radiation Oncology，Fei County People's Hospital

Feixian, Shandong, China

Location

Department of Radiation Oncology, Affiliated hospital of Jining Medical University

Jining, Shandong, China

Location

Taizhou hospital of Wenzhou Medical University

Taizhou, Zhejiang, 317000, China

Location

Related Publications (10)

• Park S, Oh D, Choi YL, Chi SA, Kim K, Ahn MJ, Sun JM. Durvalumab and tremelimumab with definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma. Cancer. 2022 Jun 1;128(11):2148-2158. doi: 10.1002/cncr.34176. Epub 2022 Mar 23.

  PMID: 35319779 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.

  PMID: 36990609 BACKGROUND

• Tachihara M, Tsujino K, Ishihara T, Hayashi H, Sato Y, Kurata T, Sugawara S, Shiraishi Y, Teraoka S, Azuma K, Daga H, Yamaguchi M, Kodaira T, Satouchi M, Shimokawa M, Yamamoto N, Nakagawa K; West Japan Oncology Group (WJOG). Durvalumab Plus Concurrent Radiotherapy for Treatment of Locally Advanced Non-Small Cell Lung Cancer: The DOLPHIN Phase 2 Nonrandomized Controlled Trial. JAMA Oncol. 2023 Nov 1;9(11):1505-1513. doi: 10.1001/jamaoncol.2023.3309.

  PMID: 37676681 BACKGROUND

• Ohri N, Jolly S, Cooper BT, Kabarriti R, Bodner WR, Klein J, Guha C, Viswanathan S, Shum E, Sabari JK, Cheng H, Gucalp RA, Castellucci E, Qin A, Gadgeel SM, Halmos B. Selective Personalized RadioImmunotherapy for Locally Advanced Non-Small-Cell Lung Cancer Trial (SPRINT). J Clin Oncol. 2024 Feb 10;42(5):562-570. doi: 10.1200/JCO.23.00627. Epub 2023 Nov 21.

  PMID: 37988638 BACKGROUND

• Li C, Tan L, Liu X, Wang X, Zhou Z, Chen D, Feng Q, Liang J, Lv J, Wang X, Bi N, Deng L, Wang W, Zhang T, Ni W, Chang X, Han W, Gao L, Wang S, Xiao Z. Concurrent chemoradiotherapy versus radiotherapy alone for patients with locally advanced esophageal squamous cell carcinoma in the era of intensity modulated radiotherapy: a propensity score-matched analysis. Thorac Cancer. 2021 Jun;12(12):1831-1840. doi: 10.1111/1759-7714.13971. Epub 2021 May 5.

  PMID: 33949784 BACKGROUND

• Liu Y, Zheng Z, Li M, Zhang Y, Zhao F, Gong H, Lin H, Huang W, Chen X, Xu Z, Li X, Liu W, Cui Y, Zheng A, Li B. Comparison of concurrent chemoradiotherapy with radiotherapy alone for locally advanced esophageal squamous cell cancer in elderly patients: A randomized, multicenter, phase II clinical trial. Int J Cancer. 2022 Aug 15;151(4):607-615. doi: 10.1002/ijc.34030. Epub 2022 Apr 27.

  PMID: 35419831 BACKGROUND

• Ji Y, Du X, Zhu W, Yang Y, Ma J, Zhang L, Li J, Tao H, Xia J, Yang H, Huang J, Bao Y, Du D, Liu D, Wang X, Li C, Yang X, Zeng M, Liu Z, Zheng W, Pu J, Chen J, Hu W, Li P, Wang J, Xu Y, Zheng X, Chen J, Wang W, Tao G, Cai J, Zhao J, Zhu J, Jiang M, Yan Y, Xu G, Bu S, Song B, Xie K, Huang S, Zheng Y, Sheng L, Lai X, Chen Y, Cheng L, Hu X, Ji W, Fang M, Kong Y, Yu X, Li H, Li R, Shi L, Shen W, Zhu C, Lv J, Huang R, He H, Chen M. Efficacy of Concurrent Chemoradiotherapy With S-1 vs Radiotherapy Alone for Older Patients With Esophageal Cancer: A Multicenter Randomized Phase 3 Clinical Trial. JAMA Oncol. 2021 Oct 1;7(10):1459-1466. doi: 10.1001/jamaoncol.2021.2705.

  PMID: 34351356 BACKGROUND

• Chen Y, Ye J, Zhu Z, Zhao W, Zhou J, Wu C, Tang H, Fan M, Li L, Lin Q, Xia Y, Li Y, Li J, Jia H, Lu S, Zhang Z, Zhao K. Comparing Paclitaxel Plus Fluorouracil Versus Cisplatin Plus Fluorouracil in Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Cancer: A Randomized, Multicenter, Phase III Clinical Trial. J Clin Oncol. 2019 Jul 10;37(20):1695-1703. doi: 10.1200/JCO.18.02122. Epub 2019 Mar 28.

  PMID: 30920880 BACKGROUND

• You J, Zhu S, Li J, Li J, Shen J, Zhao Y, Li X, Jia L, Li Q, Yang J, Wu Y, Shen W, Wu H, Wu X, Wang X, Ren Y, He J, Lin P, Zhu G, Shi A. High-Dose Versus Standard-Dose Intensity-Modulated Radiotherapy With Concurrent Paclitaxel Plus Carboplatin for Patients With Thoracic Esophageal Squamous Cell Carcinoma: A Randomized, Multicenter, Open-Label, Phase 3 Superiority Trial. Int J Radiat Oncol Biol Phys. 2023 Apr 1;115(5):1129-1137. doi: 10.1016/j.ijrobp.2022.11.006. Epub 2022 Nov 17.

  PMID: 36402359 BACKGROUND

• Yuan Y, Luo S, Wang X, Zheng Z, Qi Q, Wang Y, Chen M, Yang H, Gu P, Du Q, Wu X, Pan W, Xu Y, Wang J. Efficacy and safety of concurrent programmed cell death protein 1 inhibitor and definitive radiotherapy with immunonutrition support in esophageal squamous cell cancer: a phase II multicenter clinical trial. Radiat Oncol. 2025 Apr 18;20(1):58. doi: 10.1186/s13014-025-02604-z.

  PMID: 40251674 DERIVED

MeSH Terms

Interventions

Radiotherapy; Immune Checkpoint Inhibitors

Intervention Hierarchy (Ancestors)

Therapeutics; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Jianyang Wang, MD

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 26, 2024
• First Posted: April 2, 2024
• Study Start: March 14, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 11, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (9)