Combination of Cadonilimab and Chemoradiotherapy in Esophageal Cancer (EC-CRT-006) (EC-CRT-006)

April 22, 2026 updated by: Mian XI, Sun Yat-sen University

Cadonilimab Combined With Induction Chemotherapy and Definitive Radiotherapy for Patients With Locally Advanced Esophageal Squamous Cell Carcinoma: a Phase II, Single-arm Trial (EC-CRT-006)

Definitive chemoradiotherapy (CRT) is the standard treatment option for unresectable locally advanced esophageal cancer. However, as high as more than 40% of patients with esophageal cancer experienced locoregional recurrence after definitive CRT. Immune checkpoint inhibitors targeting PD-1/PD-L1 and/or CTLA-4 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 esophageal cancer. The aim of this study was to evaluate the efficacy and safety of cadonilimab (a bispecific PD-1/CTLA-4 antibody) combined with induction chemotherapy followed by definitive radiotherapy in patients with locally advanced esophageal squamous cell carcinoma.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

A total of 46 patients with unresectable, locally advanced ESCC will be enrolled to receive cadonilimab plus induction chemotherapy followed by definitive radiotherapy and then 12 additional cycles of maintenance therapy with cadonilimab.

Patients will receive 2 cycles of 3-weekly schedule of induction chemotherapy, consisting of paclitaxel 135 mg/m2, cisplatin 75 mg/m2, and cadonilimab 10 mg/kg on day 1 prior to CRT. Then all patients will receive standard fractionation radiation therapy scheme: 50.4 Gy in 28 fractions, concurrently with 2 cycles of cadonilimab. After the completion of radiotherapy, patients will then receive 12 additional cycles of cadonilimab.

Study Type

Interventional

Enrollment (Estimated)

46

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 Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Sun Yat-sen University

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Histologically confirmed squamous cell carcinoma of the esophagus;
  2. Locally advanced, and absence of distant metastasis disease, confirmed by endoscopic ultrasound (EUS) and PET-CT scan, stage II-IVA (according to UICC TNM version 8);
  3. Not suitable for surgery (either for medical reasons or patient's choice);
  4. Age at diagnosis 18 to 75 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 distant 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. Female patients who are pregnant or lactating;
  6. Inability to provide informed consent due to psychological, familial, social and other factors;
  7. Presence of CTC grade ≥2 peripheral neuropathy;
  8. A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer
  9. A history of diabetes for more than 10 years and poorly controlled blood glucose levels;
  10. Patients who cannot tolerate chemoradiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia.
  11. 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;
  12. A history of interstitial lung disease or non-infectious pneumonia;
  13. 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;
  14. 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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: The study group
Patients will receive 2 cycles of 3-weekly schedule of induction chemotherapy, consisting of paclitaxel 135 mg/m2, cisplatin 75 mg/m2, and cadonilimab 10 mg/kg on day 1 prior to CRT. Then all patients will receive standard fractionation radiation therapy scheme: 50.4 Gy in 28 fractions, concurrently with 2 cycles of cadonilimab. After the completion of radiotherapy, patients will then receive 12 additional cycles of cadonilimab.
Drug: Cadonilimab
Patients received cadonilimab 10 mg/kg every 3 weeks for up to 16 cycles.
Other Names:
  • AK104
Drug: Paclitaxel and cisplatin
Patients received 2 cycles of induction chemotherapy with paclitaxel/cisplatin (paclitaxel 135 mg/m2 and cisplatin 75 mg/m2) prior to radiotherapy. Then patients will not receive chemotherapy during radiotherapy.
Other Names:
  • taxol, DDP
Radiation: intensity-modulated radiotherapy
All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is 50.4 Gy in 28 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.
Clinical complete response
Time Frame: 3 months after radiotherapy (plus or minus 7 days)
Tumor response was evaluated 3 months after the completion of treatment based on CT or PET-CT scans, and endoscopy with biopsies.
3 months after radiotherapy (plus or minus 7 days)
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.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between immune signature and 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 survival outcomes.
From date of enrollment to the date of last follow-up, assessed up to 36 months.
Correlation between dynamic change of ctDNA and survival
Time Frame: From date of enrollment to the date of last follow-up, assessed up to 36 months.
The correlation between dynamic change of ctDNA during treatment and survival outcomes.
From date of enrollment to the date of last follow-up, assessed up to 36 months.
Correlation between genetic biomarkers and survival
Time Frame: From date of enrollment to the date of last follow-up, assessed up to 36 months.
The correlation between baseline genetic biomarkers by whole-exome sequencing and RNA-sequencing and immune-related adverse event, clinical response, and survival outcomes.
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

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 2, 2024

Primary Completion (Estimated)

June 10, 2026

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

November 15, 2023

First Submitted That Met QC Criteria

November 20, 2023

First Posted (Actual)

November 22, 2023

Study Record Updates

Last Update Posted (Actual)

April 23, 2026

Last Update Submitted That Met QC Criteria

April 22, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B2023-425

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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