A Study of IO Plus Radiotherapy in Patients With Advanced ESCC.

A Trial of Combination and Timing of Immunotherapy With Radiotherapy in Patients With Advanced Esophageal Squamous Cell Carcinoma.

This study is a single-arm, prospective, phase II trial for patients with metastatic esophageal squamous cell carcinoma (ESCC) who received immunotherapy plus chemotherapy as the first-line treatment. The aim of the study is to determine if intervening with combined local therapy and immunotherapy and chemotherapy in patients with ESCC led to significant improvements in survival and disease control compared with historical data.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Radiation: Radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Qi Liu, M.D.; Phone Number: 86-18017317882; Email: 18017317882@163.com
• Study Contact Backup: Name: Kuaile Zhao, M.D.

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Kuaile Zhao; Phone Number: 86-18017312534; Email: kuaile_z@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-80, had an Eastern Cooperative Oncology Group performance status score of 0-1;
2. Patients had unresectable or recurrent esophageal squamous cell carcinoma that precluded esophagectomy or definitive chemoradiation, or distant metastatic disease;
3. Patients had received no previous systemic therapy (patients who had progressed ≥6 months after [neo]adjuvant therapy or definitive chemoradiation were eligible);
4. Patients accepted at least one cycle of anti-PD-1 immunotherapy combined chemotherapy as 1st line treatment.
5. All lesions of current diagnosis did not receive local treatment such as radiotherapy, surgery, radiofrequency ablation before enrollment.
6. The measurable lesion was determined by the investigator based on the RECIST 1.1 assessment. A lesion located in a previous radiotherapy area can be considered a target lesion if it is confirmed to progress and is considered to be measurable according to RECIST 1.1.
7. Estimated survival time >12 weeks.

8. The function of vital organs meets the following requirements:

   Neutrophil absolute count (ANC) ≥ 1.5 × 10^9 / L platelets ≥ 100 × 10^9 / L; Hemoglobin ≥ 9g / dL; serum albumin ≥ 2.8g / dL; Total bilirubin ≤ 1.5 × ULN, ALT, AST and / or AKP ≤ 2.5 × ULN; if there is liver metastasis, ALT and / or AST ≤ 5 × ULN; if there is liver metastasis or bone metastasis AKP ≤ 5 × ULN; serum creatinine ≤ 1.5 × ULN or creatinine clearance > 60 mL / min; For patients with pulmonary lesions or previous lung irradiation who are known or suspected to have impaired lung function, the forced expiratory volume (FEV1) for 1 second of lung function must be above 1L.

9. Female subjects of childbearing age must have a negative urine or serum pregnancy test within 72 hours prior to randomization. Subjects agreed to adequate contraception during the trial.
10. The patient is voluntarily enrolled and obtained the informed consent form signed by the patient or his legal representative.

Exclusion Criteria:

1. Patients who are prior exposure to immune-mediated therapy.
2. Patients participated in any investigational drug study within 4 weeks preceding the start of treatment.
3. The toxicity of previous anti-tumor treatment has not recovered to ≤ National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 level 1 (except for hair loss) or the level specified by the inclusion/exclusion criteria.
4. Patients with uncontrolled brain metastases, or vertebral body metastasis with spinal cord compression symptoms.
5. Patients with uncontrolled pleural, pericardial or pelvic effusion that requires repeated drainage.
6. Patients with history of immunodeficiency, or severe medical diseases that are not well controlled, which may have effect on the treatment of this study.
7. Any other malignant tumor was diagnosed within 5 years prior to or after the diagnosis of ESCC, except for malignant tumors with a low risk of metastasis and death (5-year survival rate >90%), such as well-treated basal cells or squamous cell skin cancer or cervical cancer in situ.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Patients will be treated with anti-PD-1 Immune Checkpoint Inhibitors combined with chemotherapy used as 1st line treatment for metastatic ESCC.Radiotherapy will be conducted after four cycles of IO plus chemotherapy or started simultaneously.	Radiation: Radiotherapy; IMRT or SABR for patients with ESCC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS from start of 1st line treatment in metastatic ESCC	Median OS and OS rate at 12 months and 24 months will be analysed based on Kaplan-Meier method and presented along with its 95% confidence interval.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS from start of 1st line treatment in metastatic ESCC	Median PFS and PFS rate at 6 months, 12months and 18 months will be analysed based on Kaplan-Meier method and presented along with its 95% confidence interval.	18 months
Disease control rate	the ratio of patients with the best therapeutic evaluation is CR, PR and SD	Evaluation at the end of radiotherapy and after every 2 months of systemic therapy.

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2023
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: February 27, 2023
• First Submitted That Met QC Criteria: February 27, 2023
• First Posted (Actual): March 8, 2023

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 23, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma
• Other Study ID Numbers: ESO-Shanghai 19

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