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

March 10, 2024 updated by: Mian XI, Sun Yat-sen University

Efficacy and Safety of Toripalimab After Concurrent Chemoradiotherapy in Elderly Patients With Esophageal Squamous Cell Carcinoma: a Multicenter, Randomized, Phase II Trial (EC-CRT-007)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

140

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Drug: S-1
Patients received S-1 administration, 70mg/m2 per day, orally on days 1 to 14 and 29 to 42 during radiotherapy.
Other Names:
  • Tegafur,Gimeracil and Oteracil Potassium Capsules
Radiation: 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.
Other Names:
  • IMRT
Experimental: 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.
Drug: S-1
Patients received S-1 administration, 70mg/m2 per day, orally on days 1 to 14 and 29 to 42 during radiotherapy.
Other Names:
  • Tegafur,Gimeracil and Oteracil Potassium Capsules
Drug: Toripalimab
Patients received toripalimab 240 mg every 3 weeks for up to 16 cycles.
Other Names:
  • Toripalimab Injection
Radiation: 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.
Other Names:
  • IMRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: 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
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 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
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.
Duration of response
Time Frame: 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.
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
Time Frame: 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.
From date of enrollment to the date of last follow-up, assessed up to 36 months.
Clinical complete response
Time Frame: 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.
13-16 weeks after the completion of radiotherapy

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between immune signature and overall survival
Time Frame: From date of enrollment to the date of last follow-up, assessed up to 36 months.
The correlation between pretreatment immune signature (PD-L1, CD8, CTLA-4, CD56, and CD68) by mIHC 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
Time Frame: From date of enrollment to the date of last follow-up, assessed up to 36 months.
The correlation between dynamic change of serum cytokines (IL-2R, IL-6, IL-13, IL-8, CCL3, CD40, and CD274) during treatment and survival outcomes and immune-related adverse events.
From date of enrollment to the date of last follow-up, assessed up to 36 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Collaborators

Xiangya Hospital of Central South University
Wuhan University
Zhujiang Hospital
Fifth Affiliated Hospital, Sun Yat-Sen University
Nanfang Hospital, Southern Medical University

Investigators

  • Principal Investigator: Mian Xi, MD, Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

December 16, 2023

First Submitted That Met QC Criteria

December 29, 2023

First Posted (Actual)

January 2, 2024

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 10, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B2023-503

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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