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Minimally Residual of Esophageal Cancer 001 (ECMRD-001)

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ClinicalTrials.gov Identifier: NCT05952661
Recruitment Status : Recruiting
First Posted : July 19, 2023
Last Update Posted : July 19, 2023
Sponsor:
Information provided by (Responsible Party):
Hebei Medical University Fourth Hospital

Study Description
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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.

Condition or disease
Esophageal Carcinoma Minimal Residual Disease

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.
Study Design
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Study Type : Observational
Estimated Enrollment : 56 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Minimal Residual Disease Guided Radical Chemoradiotherapy Combined With Immunotherapy After Neoadjuvant Immunochemotherapy Followed by Adjuvant Immunotherapy for Esophageal Squamous Cell Cancer
Actual Study Start Date : February 22, 2023
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : December 31, 2027

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Outcome Measures
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Primary Outcome Measures :
  1. Correlations of minimal residual disease (MRD) and efficacy [ Time Frame: 2023/2/22-2027/12/31 ]
    The changes in MRD status before and after radical CCRT combined with immunotherapy and adjuvant immunochemotherapy in patients with inoperable resectable stage II-III ESCC, correlating with the efficacy of adjuvant immunotherapy


Secondary Outcome Measures :
  1. 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 [ Time Frame: 2023/2/22-2027/12/31 ]
    Differences in overall survival (OS) and progression-free survival (PFS) between MRD positive and negative patients after neoadjuvant immunochemotherapy. OS is defined as time from start of treatment to death (from any cause). PFS is defined as the time between the start of treatment and the onset of (any aspect of) tumor progression or death (from any cause).

  2. The differences in the immune microenvironment in patients with different efficacy responses after radical CCRT combined with immunotherapy [ Time Frame: 2023/2/22-2027/12/31 ]
    MRD status and T-lymphocyte differences across efficacy responses after receiving radical CCRT combined with immunotherapy. Therapeutic response is evaluated according to immune-related response evaluation criteria in solid tumors (irRECIST).

  3. The differences in MRD status between radiation doses of 50Gy and 60Gy, and the correlation with patient prognosis [ Time Frame: 2023/2/22-2027/12/31 ]
    The differences in MRD status between radiation doses of 50Gy and 60Gy, and the correlation with patient prognosis.

  4. The association between serial changes in MRD status and the efficacy of adjuvant immunotherapy [ Time Frame: 2023/2/22-2027/12/31 ]
    The association between serial changes in MRD status and the efficacy of adjuvant immunotherapy. Therapeutic response is evaluated according to immune-related response evaluation criteria in solid tumors (irRECIST).

  5. The timing of MRD advance warning of recurrence in patients ahead of imaging cues [ Time Frame: 2023/2/22-2027/12/31 ]
    The timing of MRD advance warning of recurrence in patients ahead of imaging cues


Other Outcome Measures:
  1. ctDNA mutation profiles in ESCC patients undergoing adjuvant immunotherapy. [ Time Frame: 2023/2/22-2027/12/31 ]
    High-frequency mutated genes in the ESCC patients undergoing adjuvant immunotherapy and the corresponding mutation frequency (percentage of samples with mutations out of all samples).


Biospecimen Retention:   Samples With DNA
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. The investigators will test circulating tumor DNA (ct-DNA) based minimal residual disease (MRD) indicators for research

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05952661


Contacts
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Contact: Wenbin Shen, PhD +86 15831183879 wbshen1979@sina.com
Contact: Hesong Wang, PhD +86 18810775196 wanghesongmz@163.com

Locations
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China, Hebei
Fourth Hospital of Hebei Medical University Recruiting
Shijiazhuang, Hebei, China, 050011
Contact: Wenbin Shen, PhD    +86 15831183879    wbshen1979@sina.com   
Contact: Hesong Wang, PhD    +86 18810775196    wanghesongmz@163.com   
Sponsors and Collaborators
Hebei Medical University Fourth Hospital
Investigators
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Principal Investigator: Wenbin Shen, PhD Hebei Medical University Fourth Hospital
More Information
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Responsible Party: Hebei Medical University Fourth Hospital
ClinicalTrials.gov Identifier: NCT05952661    
Other Study ID Numbers: ECMRD-001
First Posted: July 19, 2023    Key Record Dates
Last Update Posted: July 19, 2023
Last Verified: June 2023

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hebei Medical University Fourth Hospital:
circulating tumor DNA
ctDNA
minimal residual disease
MRD
esophageal cancer
 esophageal carcinoma
neoadjuvant immunochemotherapy
chemoradiotherapy
adjuvant immunotherapy
Additional relevant MeSH terms:
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Neoplasm, Residual
Esophageal Neoplasms
Neoplasms
Neoplastic Processes
Pathologic Processes
Gastrointestinal Neoplasms
 Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases