Consolidation of Toripalimab After Chemoradiotherapy in Elderly Esophageal Cancer (EC-CRT-007)

NCT06187597 | Recruiting Phase 2 DMC

• 1 other identifier: B2023-503
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

Although definitive chemoradiotherapy (CRT) is the standard treatment option for unresectable locally advanced esophageal cancer, elderly patients tolerate intravenous concurrent CRT less well with age and comorbidities. Previous trials have demonstrated that CRT with oral S-1 was tolerable and provided significant survival benefits over radiotherapy alone in elderly patients with esophageal squamous cell carcinoma (ESCC). However, as high as 54% of patients with elderly ESCC experienced locoregional or distant recurrence after CRT. Therefore, a more effective regimen for older patients is needed. Immune checkpoint inhibitors targeting PD-1/PD-L1 have shown substantial clinical benefits in advanced esophageal cancer. Recently, the combination of immunotherapy with CRT has emerged as a promising strategy to improve clinical outcomes in locally advanced esophageal cancer. The aim of this study was to evaluate the efficacy and safety of toripalimab (an anti-PD-1 antibody) after concurrent CRT in elderly patients with locally advanced ESCC.

Conditions

Locally Advanced Esophageal Squamous Cell Carcinoma

Keywords

Esophageal squamous cell carcinoma; Chemoradiotherapy; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Three-year follow-up from the date of enrollment to the date of disease progression or last follow-up

  From date of enrollment until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 36 months.

Secondary Outcomes (4)

• Overall survival

  From date of enrollment until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 36 months.

• Clinical complete response

  13-16 weeks after the completion of radiotherapy

• Duration of response

  From date of first CR/PR to the date of first PD according to RECIST criteria, assessed up to 36 months.

• Treatment-related adverse events

  From date of enrollment to the date of last follow-up, assessed up to 36 months.

Other Outcomes (2)

• Correlation between immune signature and overall survival

  From date of enrollment to the date of last follow-up, assessed up to 36 months.

• Correlation between serum cytokines and overall survival and immune-related adverse events

  From date of enrollment to the date of last follow-up, assessed up to 36 months.

Study Arms (2)

The study group

EXPERIMENTAL

Patients will receive radiotherapy with prescribed dose of 54 Gy in 27 fractions, concurrently with S-1 chemotherapy. Then patients in the study group will receive toripalimab as consolidation therapy for up to 12 months (16 cycles) after the completion of chemoradiotherapy.

Drug: S-1; Drug: Toripalimab; Radiation: Intensity-modulated radiotherapy

The control group

ACTIVE COMPARATOR

Patients will receive radiotherapy with prescribed dose of 54 Gy in 27 fractions, concurrently with S-1 chemotherapy. Then patients will be receive routine follow-up.

Drug: S-1; Radiation: Intensity-modulated radiotherapy

Interventions

S-1 DRUG

Patients received S-1 administration, 70mg/m2 per day, orally on days 1 to 14 and 29 to 42 during radiotherapy.

Also known as: Tegafur,Gimeracil and Oteracil Potassium Capsules

The control group; The study group

Toripalimab DRUG

Patients received toripalimab 240 mg every 3 weeks for up to 16 cycles.

Also known as: Toripalimab Injection

The study group

Intensity-modulated radiotherapy RADIATION

All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is 54 Gy in 27 fractions over 5-6 weeks.

Also known as: IMRT

The control group; The study group

Eligibility Criteria

• Age: 70 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Histologically confirmed squamous cell carcinoma of the esophagus;
• Locally advanced, and absence of hematogenous metastasis disease according to UICC TNM version 8;
• Not suitable for surgery (either for medical reasons or patient's choice);
• Age at diagnosis 70 to 85 years;
• No prior cancer therapy;
• Estimated life expectancy \>6 months;
• Eastern Cooperative Oncology Group performance status ≤ 2
• No history of concomitant or previous malignancy;
• The function of important organs meets the following requirements: a. white blood cell count (WBC) ≥4.0×109/L, absolute neutrophil count (ANC) ≥1.5×109/L; b. platelets ≥100×109/L; c. hemoglobin ≥9g/dL; d. serum albumin ≥2.8g/dL; e. total bilirubin ≤1.5×ULN, ALT, AST and/or AKP ≤2.5×ULN; f. serum creatinine ≤1.5×ULN or creatinine clearance rate \>60 mL/min;
• Ability to understand the study and sign informed consent.

You may not qualify if:

• Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.);
• Patients with hematogenous metastasis disease or esophageal fistula at diagnosis;
• Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of cadonilimab, and the chemotherapeutic drugs paclitaxel or cisplatin;
• Patients who have a preexisting or coexisting bleeding disorder;
• Inability to provide informed consent due to psychological, familial, social and other factors;
• Presence of CTC grade ≥2 peripheral neuropathy;
• A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer
• A history of diabetes for more than 10 years and poorly controlled blood glucose levels;
• Patients who cannot tolerate chemoradiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia.
• Active autoimmune diseases, a history of autoimmune diseases (including but not limited to these diseases or syndromes, such as colitis, hepatitis, hyperthyroidism), a history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases, a history of organ transplantation or allogeneic bone marrow transplantation;
• A history of interstitial lung disease or non-infectious pneumonia;
• A history of active pulmonary tuberculosis infection within 1 year or a history of active pulmonary tuberculosis infection more than 1 year ago but without formal anti-tuberculosis treatment;
• Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay).

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Nanfang Hospital, Southern Medical University: collaborator
• Zhujiang Hospital: collaborator
• Fifth Affiliated Hospital, Sun Yat-Sen University: collaborator
• Xiangya Hospital of Central South University: collaborator
• Wuhan University: collaborator

Study Sites (1)

Mian Xi

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (4)

• 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 RESULT

• 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 RESULT

• 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 RESULT

• Wang X, Han W, Zhang W, Wang X, Ge X, Lin Y, Zhou H, Hu M, Wang W, Liu K, Lu J, Qie S, Zhang J, Deng W, Wang L, Han C, Li M, Zhang K, Li L, Wang Q, Shi H, Yu Z, Zhao Y, Sun X, Shi Y, Pang Q, Zhou Z, Liang J, Chen D, Feng Q, Bi N, Zhang T, Deng L, Wang W, Liu W, Wang J, Zhai Y, Wang J, Chen W, Chen J, Xiao Z; Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG). Effectiveness of S-1-Based Chemoradiotherapy in Patients 70 Years and Older With Esophageal Squamous Cell Carcinoma: A Randomized Clinical Trial. JAMA Netw Open. 2023 May 1;6(5):e2312625. doi: 10.1001/jamanetworkopen.2023.12625.

  PMID: 37195667 RESULT

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

S 1 (combination); Tegafur; gimeracil; potassium oxonate; toripalimab; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Fluorouracil; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Mian Xi, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mian Xi, MD

CONTACT

862087343385; ximian@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 16, 2023
• First Posted: January 2, 2024
• Study Start: March 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 12, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)