Clinical trial NCT05952661: Minimally Residual of Esophageal Cancer 001
Official title: Minimal Residual Disease Guided Radical Chemoradiotherapy Combined With Immunotherapy After Neoadjuvant Immunochemotherapy Followed by Adjuvant Immunotherapy for Esophageal Squamous Cell Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Esophageal Carcinoma
Minimal Residual Disease
Keywords: circulating tumor DNA
ctDNA
minimal residual disease
MRD
esophageal cancer
esophageal carcinoma
neoadjuvant immunochemotherapy
chemoradiotherapy
adjuvant immunotherapy
Lead sponsor: Hebei Medical University Fourth Hospital
Sponsor class: OTHER
First posted: 2023-07-19
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Esophageal squamous cell cancer patients who receive radical chemoradiotherapy combined with immunotherapy after neoadjuvant immunochemotherapy followed by adjuvant immunotherapy.

Brief summary: This trial aims to assess changes in minimal residual disease (MRD) status before and after radical concurrent chemoradiotherapy combined with immunotherapy and adjuvant immunotherapy after neoadjuvant immunochemotherapy in patients with inoperable stage II-III esophageal squamous cell cancer (ESCC), and correlate with the efficacy of adjuvant immunotherapy.

Detailed description: Presence of circulating tumor DNA (ctDNA) is indicative for minimal residual disease (MRD) and has high predictive value for efficacy and tumor recurrence. Concurrent chemoradiotherapy becomes the standard of care for unresectable, locally advanced esophageal squamous cell cancer, and the addition of immunotherapy to radiotherapy has been shown to increase efficacy without increasing side effects. The ECMRD-001 trial aims to assess changes in MRD status before and after radical concurrent chemoradiotherapy combined with immunotherapy and adjuvant immunotherapy after neoadjuvant immunochemotherapy in patients with inoperable stage II-III esophageal squamous cell cancer (ESCC). The specimen collection time points were divided into MRD-related blood collections, MRD-related tissue collection, T-cell immunohistobank-related blood collections, and T-cell immunohistobank-related tissue collection before, during, and after treatment and follow-up. Primary endpoint is the relationship between MRD status at different time points and treatment efficacy. Secondary endpoints include the relationship between MRD status and immune microenvironment, radiotherapy dose, and tumor recurrence. Exploratory endpoint is to investigate ctDNA mutations in ESCC patients receiving adjuvant immunotherapy. To the investigators' knowledge, the ECMRD-001 study is the first clinical trial to investigate ctDNA-based MRD guided strategies in stage II-III ESCC patients who receive radical chemoradiotherapy combined with immunotherapy after neoadjuvant immunochemotherapy followed by adjuvant immunotherapy. After our research it may be possible to confirm that ctDNA-based MRD may be a predictive marker for the efficacy and tumor recurrence of inoperable ESCC patients; elevated ctDNA-MRD may predict tumor recurrence earlier than imaging; ctDNA-based MRD analysis and ctDNA-based MRD guided diagnosis and treatment may be implemented into clinical practice to improve efficacy and reduce tumor recurrence of inoperable stage II-III ESCC.

Eligibility criteria: Inclusion Criteria:

1. age: 18 - 75 years
2. gender: both sexes, as balanced as possible
3. patients with clinically confirmed TNM 8th stage II-III ESCC by histopathology and are not suitable for surgery
4. patients receive neoadjuvant immunochemotherapy, followed by radical CCRT combined with immunotherapy and finally adjuvant immunotherapy
5. Eastern Cooperative Oncology Group (ECOG) score: 0-1
6. the functional condition of the organ meets the following requirements- haematological indicators: absolute neutrophil count ≥ 1.5 \* 109/L, platelet count ≥ 100 \* 109/L, haemoglobin count≥ 9 g/dL; good coagulation: platelet count ≥ 100 x 109/L. Liver: total bilirubin ≤ 2 times the upper limit of normal, ghrelin and ghrelin ≤ 2.5 times the upper limit of normal. Renal: creatinine ≤ 1.5 times the upper limit of normal, or creatinine clearance ≥ 60 mL/min (calculated by the Cockcroft-Gault formula)
7. women of childbearing age must have a urine pregnancy test with a negative result within 7 days prior to starting treatment
8. patients understand and voluntarily sign the informed consent form

Exclusion Criteria:

* (1) patients have been diagnosed or treated for another malignancy within 5 years prior to the start of this study (2) adenocarcinoma, mixed adenosquamous or other pathological types of esophageal cancer (3) any unstable systemic disease, including: active infection, uncontrolled hypertension, unstable angina, angina pectoris starting within the last 3 months, congestive heart failure (≥ New York Heart Association \[NYHA\] class II), myocardial infarction (6 months prior to enrollment), severe arrhythmia requiring medication, liver, kidney or metabolic disease (4) with known or suspected active autoimmune disease (5) previous treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or anti-CTLA-4 antibodies or any other antibodies or drugs that specifically target T-cell co-stimulation or checkpoint pathways (6) known history of testing positive for human immunodeficiency virus (HIV) or known to have acquired immunodeficiency syndrome (AIDS) (7) female patients who are pregnant or breastfeeding (8) other conditions deemed unsuitable for enrolment by the investigator

Primary outcomes:
measure: Correlations of minimal residual disease (MRD) and efficacy
timeFrame: 2023/2/22-2027/12/31
Secondary outcomes:
measure: The differences in the efficacy of neoadjuvant immunochemotherapy in patients with positive versus negative blood MRD prior to radical concurrent chemoradiotherapy (CCRT) combined with immunotherapy following neoadjuvant immunochemotherapy
timeFrame: 2023/2/22-2027/12/31
measure: The differences in the immune microenvironment in patients with different efficacy responses after radical CCRT combined with immunotherapy
timeFrame: 2023/2/22-2027/12/31
measure: The differences in MRD status between radiation doses of 50Gy and 60Gy, and the correlation with patient prognosis
timeFrame: 2023/2/22-2027/12/31
measure: The association between serial changes in MRD status and the efficacy of adjuvant immunotherapy
timeFrame: 2023/2/22-2027/12/31
measure: The timing of MRD advance warning of recurrence in patients ahead of imaging cues
timeFrame: 2023/2/22-2027/12/31
Other outcomes:
measure: ctDNA mutation profiles in ESCC patients undergoing adjuvant immunotherapy.
timeFrame: 2023/2/22-2027/12/31
Locations:
city: Shijiazhuang
country: China
facility: Fourth Hospital of Hebei Medical University
state: Hebei
Study officials:
affiliation: Hebei Medical University Fourth Hospital
name: Wenbin Shen, PhD
role: PRINCIPAL_INVESTIGATOR
References: