MRD-Guided Consolidation Therapy Following Definitive Radiotherapy in Esophageal Cancer

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.

Первичные конечные точки

• Median progression-free survival (PFS) [Срок оценки: 36 month]

Вторичные конечные точки (5)

• 5-year overall survival [Срок оценки: 60 month]
• Cancer specific survival [Срок оценки: 60 month]
• Incidence of radiotherapy and immunotherapy related toxicity [Срок оценки: Through study completion, an average of 3 year]
• Quality of life score(QOL) for swallowing function [Срок оценки: 36 month]
• General Quality of life score(QOL) [Срок оценки: 36 month]

Критерии участия

Критерии включения

• ≥18 years, any gender
• 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
• ECOG performance status <= 1.
• No significant abnormality in laboratory routine indicators such as blood routine and liver and kidney function
• Completed radical radiotherapy (dose 50-60Gy);
• 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;
• Informed consent

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Cancer hospital, CAMS — Пекин

Идентификаторы

NCT: NCT06498752 · BEIR 2

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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