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

NCT ID: NCT06187597

Last Updated: 2024-03-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-01
• Study Completion Date: 2028-12-31

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.

Detailed Description

A total of 140 patients with elderly, unresectable, locally advanced ESCC will be stratified according to age (70-80 vs. ≥80) and TNM stage (I/II vs. III/IV) and randomly assigned (1:1) to receive toripalimab as consolidation therapy for up to 12 months (arm A) or not (arm B) after definitive radiotherapy with concurrent S-1.

Conditions

Locally Advanced Esophageal Squamous Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

The study group

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.

Group Type: EXPERIMENTAL

S-1

Intervention Type: DRUG

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

Toripalimab

Intervention Type: DRUG

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

Intensity-modulated radiotherapy

Intervention Type: RADIATION

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

The control group

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.

Group Type: ACTIVE_COMPARATOR

S-1

Intervention Type: DRUG

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

Intensity-modulated radiotherapy

Intervention Type: RADIATION

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

Interventions

S-1

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

Intervention Type: DRUG

Toripalimab

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

Intervention Type: DRUG

Intensity-modulated radiotherapy

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

Intervention Type: RADIATION

Other Intervention Names

Tegafur,Gimeracil and Oteracil Potassium Capsules; Toripalimab Injection; IMRT

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed squamous cell carcinoma of the esophagus;

2. Locally advanced, and absence of hematogenous metastasis disease according to UICC TNM version 8;

3. Not suitable for surgery (either for medical reasons or patient's choice);

4. Age at diagnosis 70 to 85 years;

5. No prior cancer therapy;

6. Estimated life expectancy >6 months;

7. Eastern Cooperative Oncology Group performance status ≤ 2

8. No history of concomitant or previous malignancy;

9. 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;

10. Ability to understand the study and sign informed consent.

Exclusion Criteria

1. Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.);

2. Patients with hematogenous metastasis disease or esophageal fistula at diagnosis;

3. Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of cadonilimab, and the chemotherapeutic drugs paclitaxel or cisplatin;

4. Patients who have a preexisting or coexisting bleeding disorder;

5. Inability to provide informed consent due to psychological, familial, social and other factors;

6. Presence of CTC grade ≥2 peripheral neuropathy;

7. A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer

8. A history of diabetes for more than 10 years and poorly controlled blood glucose levels;

9. Patients who cannot tolerate chemoradiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia.

10. 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;

11. A history of interstitial lung disease or non-infectious pneumonia;

12. 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;

13. 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).

• Minimum Eligible Age: 70 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role: collaborator

Zhujiang Hospital

OTHER

Sponsor Role: collaborator

Fifth Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role: collaborator

Xiangya Hospital of Central South University

OTHER

Sponsor Role: collaborator

Wuhan University

OTHER

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Mian XI

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mian Xi, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Mian Xi

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Mian Xi, MD

Role: CONTACT

ximian@sysucc.org.cn

862087343385

Facility Contacts

Mian Xi, MD

Role: primary

ximian@sysucc.org.cn

862087343385

References

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.

Reference Type: RESULT

PMID: 36990609 (View on PubMed)

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.

Reference Type: RESULT

PMID: 34351356 (View on PubMed)

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.

Reference Type: RESULT

PMID: 35419831 (View on PubMed)

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.

Reference Type: RESULT

PMID: 37195667 (View on PubMed)

Other Identifiers

B2023-503

Identifier Type: -

Identifier Source: org_study_id