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

Phase 2

Recruiting

• Conditions: Locally Advanced Esophageal Squamous Cell Carcinoma
• Interventions: Drug: S-1; Drug: Toripalimab; Radiation: Intensity-modulated radiotherapy

• Registration Number: NCT06187597
• Lead Sponsor: Sun Yat-sen University

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.

Study Timeline

• Study First Submitted: 2023-12-16
• Study First Submitted QC: 2023-12-29
• Study First Posted: 2024-01-02
• Status Verified: 2024-03
• Study Start: 2024-03-01
• Last Update Submitted: 2024-03-10
• Last Update Posted: 2024-03-12
• Primary Completion: 2026-12-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 140

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
The study group	Intensity-modulated radiotherapy	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.
The control group	Intensity-modulated radiotherapy	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.
The control group	S-1	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.
The study group	Toripalimab	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.
The study group	S-1	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.

Primary Outcome Measures

Name	Time	Method
Progression-free survival	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.	Three-year follow-up from the date of enrollment to the date of disease progression or last follow-up

Secondary Outcome Measures

Name	Time	Method
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.	Three-year follow-up from the enrollment to the date of death from any cause or date of lost follow-up
Clinical complete response	13-16 weeks after the completion of radiotherapy	Tumor response was evaluated 13-16 weeks after the completion of treatment based on CT or PET-CT scans, and endoscopy with biopsies.
Duration of response	From date of first CR/PR to the date of first PD according to RECIST criteria, assessed up to 36 months.	From the date of first CR/PR to the date of first PD.
Treatment-related adverse events	From date of enrollment to the date of last follow-up, assessed up to 36 months.	Incidence of treatment-related adverse events as assessed by CTCAE v4.0.

Trial Locations

Locations (1)

Mian Xi; 🇨🇳 Guangzhou, Guangdong, China