Concurrent Chemoradiotherapy for Stage IVB Esophageal Squamous Cell Carcinoma（EC-CRT-003） (EC-CRT-003)

November 15, 2023 updated by: Mian XI, Sun Yat-sen University

Systemic Therapy Combined With Thoracic Concurrent Chemoradiotherapy Versus Systemic Therapy Alone in Stage IVB Esophageal Squamous Cell Carcinoma: A Prospective Randomized Phase II Study

Retrospective studies suggested that the addition of thoracic concurrent chemoradiotherapy to systemic chemotherapy improved the survival and quality of life (QOL) of patients with metastatic esophageal squamous cell carcinoma (ESCC). However, no prospective study had been conducted to confirm these findings. Recently, immunotherapy targeting the PD-1/PD-L1 checkpoints combined with chemotherapy had been proved to significantly prolong the survival of those patients compared with chemotherapy alone. Moreover, anti-PD-1 combined with radiotherapy exerts a synergistic anti-tumor effect, which may further improve the combination efficacy. This randomized, phase II study aimed to evaluate the efficacy and safety of the chemotherapy and anti-PD-1 combined with concurrent chemoradiotherapy to primary tumor versus systemic therapy alone in stage IVB ESCC. Of note, non-regional lymph node metastasis only was the stratification factor in the random assignment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

126

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, 510000
        • Recruiting
        • Sun yat-sen University Cancer Center
        • Contact:

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

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Eastern Cooperative Oncology Group performance status ≤ 2
  2. Histologically confirmed squamous cell carcinoma of the esophagus;
  3. Diagnosed with stage IVB disease (according to UICC TNM version 8);
  4. Received 4 to 6 cycles of standard chemotherapy (fluoropyrimidine or taxane-based platinum doublet chemotherapy) and anti-PD1 treatment, and no progression disease was confirmed;
  5. Estimated life expectancy >4 months;
  6. The function of important organs meet 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;
  7. Ability to understand the study and sign informed consent.

Exclusion Criteria:

  1. Progression was confirmed after completion of 4 to 6 cycles of standard chemotherapy and anti-PD1 treatment;
  2. Patients with intracranial metastasis disease at diagnosis;
  3. History of thoracic irradiation;
  4. Known or suspected allergy or hypersensitivity to monoclonal antibodies and the chemotherapeutic drugs: Capecitabine, paclitaxel, or platinum;
  5. Patients who have a preexisting esophagomediastinal fistula and/or esophagotracheal fistula;
  6. A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer
  7. Patients who cannot tolerate chemoradiotherapy due to severe cardiac, lung, liver, or kidney dysfunction, or hematopoietic disease or cachexia.
  8. Inability to provide informed consent due to psychological, familial, social, and other factors;
  9. Female patients who are pregnant or during lactation;
  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. 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
Experimental: Concurrent Chemoradiotherapy group
After completion of 4 to 6 cycles of standard chemotherapy and anti-PD1, all patients will receive thoracic radiation therapy (RT) in the following scheme: 45 to 50.4Gy in 25 to 28 fractions, concurrently with 2 cycles of capecitabine tablets (825mg/m2) for two weeks, and then followed by a maintenance treatment phase of anti-PD1 every 3 weeks.
Combination product: Intensity-modulated radiotherapy concurrent with capecitabine
All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is 45 to 50.4Gy in 25 to 28 fractions, concurrently with 2 cycles of capecitabine tablets (825mg/m2) for two weeks.
No Intervention: Control group
After completion of 4 to 6 cycles of standard chemotherapy and anti-PD1, patients will receive the maintenance treatment with anti-PD1 every 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
1-year progression-free survival
Time Frame: From date of randomization until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 12 months
The 1-year progression-free survival of each group
From date of randomization until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
1-year overall survival
Time Frame: From date of randomization until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 12 months
The 1-year overall survival of the each group
From date of randomization until the date of death from any cause or the date of last follow-up, whichever came first, assessed up to 12 months
ORR
Time Frame: 3 months after chemoradiotherapy (plus or minus 14 days)
Overall response rate
3 months after chemoradiotherapy (plus or minus 14 days)
Treatment-related adverse events
Time Frame: From the start of treatment to 2 year after the completion of treatment
Toxicity of treatment was evaluated according to CTCAE 4.0
From the start of treatment to 2 year after the completion of treatment

Collaborators and Investigators

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

Sponsor

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)

September 20, 2022

Primary Completion (Estimated)

August 30, 2024

Study Completion (Estimated)

September 30, 2025

Study Registration Dates

First Submitted

August 21, 2022

First Submitted That Met QC Criteria

August 21, 2022

First Posted (Actual)

August 23, 2022

Study Record Updates

Last Update Posted (Estimated)

November 17, 2023

Last Update Submitted That Met QC Criteria

November 15, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-FXY-040

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

product manufactured in and exported from the U.S.

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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