MRD-Guided Consolidation Therapy Following Definitive Radiotherapy in Esophageal Cancer

A Phase II Clinical Trial of Consolidation Therapy Guided by MRD Testing After Radical Radiotherapy for Esophageal Cancer

To further validate the performance of the high-sensitivity MRD assay in patients with squamous esophageal cancer who have completed radical radiotherapy; to validate whether MRD-negative patients can maintain a good prognosis under regular follow-up; and to validate whether MRD-positive patients can improve their survival with consolidation therapy with PD-1 monotherapy.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Cancer
• Intervention / Treatment: Drug: PD-1 monoclonal antibody consolidation therapy

Detailed Description

Esophageal cancer is one of the most common lethal tumours in the world and accounts for more than 50% of new cases in China. Definitive concurrent chemoradiotherapy is the standard treatment for unresectable locally advanced esophageal cancer, and the 5-year survival rate is only about 30%, but due to the lack of evidence, consolidation therapy has not been explicitly recommended in major guidelines.

In the CheckMate 577 study, patients who did not achieve pathological complete response (pCR) after surgery improved their survival through immunology consolidation therapy with PD-1 monotherapy, suggesting that patients who did not achieve clinical complete response (cCR) after radiotherapy may benefit from immunology consolidation therapy. This suggests that patients who do not have a clinical complete response (cCR) after radiotherapy are likely to benefit from immunology consolidation therapy. Patients with cCR after radiotherapy may achieve similar results to those achieved with radical surgery, and consolidation is probably not necessary.

However, existing clinical practice is unable to accurately determine the efficacy of radiotherapy in esophageal cancer, making risk-of-recurrence-guided stratified consolidation strategies difficult to achieve. Most of the ongoing radiotherapy-immunotherapy studies in esophageal cancer have been designed to treat all patients indiscriminately with immunology consolidation therapy, which may lead to over-treatment of cCR patients.

Therefore, there is an urgent need to find easily accessible and reliable biomarkers for the efficacy of radiotherapy in esophageal cancer, and to carry out prospective clinical studies as soon as possible, so as to optimize the strategy of consolidation therapy after radiotherapy in esophageal cancer. The high sensitivity of minimal residual disease (MRD) detection technology established by the researcher's team provides a prerequisite for this.

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer hospital, CAMS
      • Contact: Email: liuwenyang@cicams.ac.cn
      • Principal Investigator: Wen-Yang Liu
      • Contact: Wen-Yang Liu, MD; Phone Number: +86-01087787654; Email: liuwenyang@cicams.ac.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. ≥18 years, any gender
2. Histologically or cytologically confirmed squamous cell carcinoma of esophageal cancer. The initial clinical stage is I-VIa (2018 AJCC Cancer Staging Manual, 8th Edition) , primary unresectable oesophageal cancer
3. ECOG performance status <= 1.
4. No significant abnormality in laboratory routine indicators such as blood routine and liver and kidney function
5. Completed radical radiotherapy (dose 50-60Gy);
6. Received a systemic regimen of platinum in combination with paclitaxel or a 5-FU-based two-drug regimen with or without PD-1 monotherapy in accordance with the CSCO guidelines, and S-1 monotherapy in elderly patients;
7. Informed consent

Exclusion Criteria:

1. Patients with other cancer history except hypopharyngeal carcinoma in situ, non-malignant skin cancer and cervical carcinoma in situ.
2. Active infection currently exists, serious illness such as myocardial infarction in the 6 months prior to enrolment
3. History of autoimmune diseases
4. Participate in other clinical trials at present or within 4 weeks before enrollment;
5. Received systemic therapy (chemotherapy alone or chemotherapy combined with immunotherapy) for more than 4 cycles.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: MRD negative; Intervention name: regular review of MRD monitoring; Intervention description: thoracic and abdominal CT, Esophagography and MRD monitoring every 3 months for 2 years after completion of radiotherapy
Experimental: MRD positive; Intervention name: PD-1 monoclonal antibody consolidation therapy;	Drug: PD-1 monoclonal antibody consolidation therapy; PD-1 monoclonal antibody-based consolidation therapy for 1 year after completion of radiotherapy (or combination chemotherapy up to 4 cycles if less than 4 cycles of chemotherapy). Specific dosing: PD-1 monoclonal antibody, 200mg every 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median progression-free survival (PFS)	Median progression-free survival (PFS), was defined as the time from the end of radiotherapy to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first.	36 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5-year overall survival	Overall survival was defined as the time from the end of radiotherapy to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS is reported for all participants of the Intent-To-Treat (ITT) population. The Kaplan-Meier method was used to calculated the 5-year survival probability.	60 month
Cancer specific survival	From the end of radiotherapy to death specifically attributed to esophageal cancer.	60 month
Incidence of radiotherapy and immunotherapy related toxicity	Acute toxicity Rate, was defined as the frequency of toxicities related to the treatment, which arises during radiotherapy and within three month after the end of radiotherapy, according to National Cancer Institute Common Terminology Criteria for Adverse Event,Version 5.0 (CTC AE5.0). Late toxicity rate, was defined as the frequency of toxicities related to the treatment, which arises three month after the end of radiotherapy, according to National Cancer Institute Common Terminology Criteria for Adverse Event,Version 5.0 (CTC AE5.0).	Through study completion, an average of 3 year
Quality of life score(QOL) for swallowing function	Evluated by the score of the participants through The EORTC Quality of Life Questionnaire - Oesophageal Cancer Module (EORTC QLQ-OES18). The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores represent a higher ("worse") level of symptoms.	36 month
General Quality of life score(QOL)	Change From Baseline in the EORTC QLQ-C30 Subscale Scores in Participants. The score of the participants evaluated by The EORTC core quality of life questionnaire (QLQ-C30). The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score represents a higher response level. Thus a high score for a functional scale represents a high/healthy level of functioning.	36 month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circulating DNA as biomarkers for the predicting of efficacy	To explore the dynamic changes of circulating tumor DNA (the frequency of specific mutations by Next-generation sequencing Methodology) from baseline, before and after radiotherapy and their relationship with recurrence.	36 months

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Collaborators: Peking University Cancer Hospital & Institute; Tianjin Medical University Cancer Institute and Hospital; Hebei Medical University Fourth Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: June 20, 2024
• First Submitted That Met QC Criteria: July 6, 2024
• First Posted (Actual): July 12, 2024

Study Record Updates

• Last Update Posted (Actual): August 6, 2024
• Last Update Submitted That Met QC Criteria: August 3, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: immunotherapy; Esophageal squamous cell carcinoma; Immune checkpoint inhibitor; chemotherapy; radiotherapy; Minimal residual disease, MRD
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: BEIR 2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No