Clinical trial NCT06498752: MRD-Guided Consolidation Therapy Following Definitive Radiotherapy in Esophageal Cancer
Official title: A Phase II Clinical Trial of Consolidation Therapy Guided by MRD Testing After Radical Radiotherapy for Esophageal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Esophageal Cancer
Keywords: Esophageal squamous cell carcinoma
Immune checkpoint inhibitor
immunotherapy
chemotherapy; radiotherapy
Minimal residual disease, MRD
Lead sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Sponsor class: OTHER
Collaborators: name: Peking University Cancer Hospital & Institute
name: Hebei Medical University Fourth Hospital
name: Tianjin Medical University Cancer Institute and Hospital
First posted: 2024-07-12
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Median progression-free survival (PFS)
timeFrame: 36 month
Secondary outcomes:
measure: 5-year overall survival
timeFrame: 60 month
measure: Cancer specific survival
timeFrame: 60 month
measure: Incidence of radiotherapy and immunotherapy related toxicity
timeFrame: Through study completion, an average of 3 year
measure: Quality of life score(QOL) for swallowing function
timeFrame: 36 month
measure: General Quality of life score(QOL)
timeFrame: 36 month
Other outcomes:
measure: Circulating DNA as biomarkers for the predicting of efficacy
timeFrame: 36 months
Locations:
city: Beijing
country: China
facility: Cancer hospital, CAMS
state: Beijing
Study officials:
References: