Trial Title:
Dynamic ctDNA Monitoring in Neoadjuvant Therapy for Esophageal Squamous Cell Carcinoma
NCT ID:
NCT06103890
Condition:
Esophageal Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Conditions: Keywords:
neoadjuvant therapy
esophageal squamous cancer
ctDNA
immunochemotherapy
dynamic monitoring
biomarker
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Summary:
This study is a prospective, multicenter, open-label, observational cohort study. The
primary endpoint is pathological complete response (pCR), and the secondary endpoints
include R0 resection rate, ctDNA clearance rate, major pathological response (MPR),
recurrence-free survival (RFS), and overall survival (OS). Chinese patients with
esophageal squamous cell carcinoma who are eligible for surgical resection will receive
neoadjuvant therapy with cetuximab combined with albumin-bound paclitaxel and nedaplatin.
Personalized ctDNA monitoring will be conducted at multiple time points, including before
neoadjuvant therapy, during therapy, preoperatively, postoperatively, and during adjuvant
therapy, to explore the clinical value of minimal residual disease (MRD) as a biomarker
for assessing treatment efficacy, predicting recurrence risk, and evaluating prognosis in
esophageal squamous cell carcinoma. This study aims to enroll 100 Chinese patients with
stage II-III (potentially) resectable esophageal squamous cell carcinoma.
Detailed description:
This study aims to enroll 100 Chinese patients with stage II-III (potentially) resectable
esophageal squamous cell carcinoma.
Tumor tissue samples will be collected from the subjects before neoadjuvant therapy for
whole-exome sequencing (WES). Based on the WES results, personalized ctDNA detection
panels will be designed (referred to as panel 1) for blood-based multiplex PCR-NGS
testing. Blood samples will be collected at baseline (T0), after the first cycle of
treatment (T1), after the second cycle of treatment (T2), after the third cycle of
treatment (T3), and after the fourth cycle of treatment (T4) for monitoring.
Intraoperative tumor tissue will be collected. For patients with tumor cell content ≥20%,
WES will be performed, and a personalized ctDNA detection panel (referred to as panel 2)
will be designed based on the WES results. For patients with tumor cell content <20%,
panel 1 will continue to be used for blood-based multiplex PCR-NGS testing. Blood samples
will be collected before surgery (T5), 3-7 days after surgery (T6), and during the
adjuvant therapy period (T7-TN) for ctDNA monitoring. MRD monitoring will be conducted
every 3-6 months during follow-up, with dynamic recurrence monitoring until radiological
recurrence or the end of the study. The stable detection limit for ctDNA monitoring is
0.02%.
It is expected to complete enrollment within 1 year. Clinical and pathological data, such
as performance status, imaging, and serum markers (e.g., CEA), will be collected during
the clinical trial. Follow-up will be conducted for 24 months, and data on treatment
regimens, recurrence-free survival (RFS), overall survival (OS), adverse events (AE),
etc., will be collected. Continuous observation will be conducted for up to 3 years.
Bioinformatics analysis will be performed on the data to construct mutation profiles.
Statistical analysis will be conducted to establish the correlation between ctDNA
positivity, mutation characteristics, and prognostic indicators. The ctDNA data analysis
results will be linked to clinical management to ultimately improve clinical care.
Treatment regimen: Neoadjuvant therapy with cetuximab combined with albumin-bound
paclitaxel and nedaplatin for 2-4 cycles:
Albumin-bound paclitaxel: 400mg, IV, on day 1, every 3 weeks; Nedaplatin: 80 mg/m2, IV,
every 3 weeks; Cetuximab: 200mg, IV, on day 1, every 3 weeks.
Criteria for eligibility:
Study pop:
Patients with stage II-III (potentially) operable esophageal squamous cell carcinoma
Sampling method:
Non-Probability Sample
Criteria:
Inclusion Criteria:
1. Age between 18 and 70 years, regardless of gender.
2. Patients with histologically confirmed clinical stage II-III thoracic esophageal
squamous cell carcinoma.
3. Neck enhanced CT scan showing no suspicious lymph node metastasis in the neck; no
systemic metastasis detected by imaging examination.
4. Expected to achieve R0 resection.
5. ECOG performance status of 0-1.
6. No prior anti-tumor treatment for esophageal cancer, including chemotherapy,
radiotherapy (including planned radiotherapy during the study period), hormone
therapy, and immunotherapy.
7. Measurable lesions (according to RECIST v1.1 criteria).
8. Preoperative evaluation of organ function shows no contraindications for surgery.
9. Laboratory tests confirm good bone marrow, liver, kidney function, and coagulation
function.
10. Able to provide informed consent and willing to cooperate with clinical follow-up.
11. Willing to provide peripheral blood samples for testing, as well as the patient's
medical history, current treatment information, imaging studies, and tumor marker
data, and willing to use the testing data for further scientific research, clinical
diagnosis and treatment, and commercial product development.
Exclusion Criteria:
1. Unable to provide a sufficient amount of tissue samples/blood samples required for
the study before treatment.
2. Patient refuses to undergo MRD testing.
3. History of malignancies other than esophageal cancer within the past 5 years
(excluding cured localized tumors, such as cervical carcinoma in situ, basal cell
carcinoma, and prostate carcinoma in situ; patients with prostate cancer who have
received hormone therapy and achieved disease-free survival for more than 5 years
are not excluded).
4. History of gastrointestinal bleeding within the past 6 months, or presence of
coagulation abnormalities at enrollment, or currently receiving thrombolytic or
anticoagulant therapy, indicating a high risk of bleeding.
5. Severe cardiovascular or cerebrovascular diseases.
6. History of interstitial lung disease or active pneumonia requiring steroid treatment
at enrollment.
7. Active tuberculosis at enrollment or received anti-tuberculosis treatment within the
past year.
8. Bronchial asthma requiring intermittent use of bronchodilators or other medical
interventions at enrollment.
9. Presence of systemic infectious diseases requiring systemic treatment within the
past 4 weeks at enrollment.
10. Severe unhealed wounds, active ulcers, or untreated fractures at enrollment.
11. Presence of other non-surgical conditions.
12. Previous surgeries that prevent the use of gastric conduit for esophageal
reconstruction.
13. Severe allergic reactions to chemotherapy drugs (such as paclitaxel, albumin-bound
paclitaxel, cisplatin, or carboplatin) or any monoclonal antibody.
14. History of organ transplantation.
15. Other conditions deemed unsuitable for participation in this study according to the
investigator's judgment.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University
Address:
City:
Shijiazhuang
Zip:
050011
Country:
China
Status:
Recruiting
Contact:
Last name:
Ziqiang Tian, MD
Phone:
18531118000
Email:
tianzq1026@163.com
Contact backup:
Last name:
Huilai Lv, MD
Phone:
13931135605
Email:
lvhl2288@163.com
Start date:
May 22, 2023
Completion date:
July 31, 2025
Lead sponsor:
Agency:
Hebei Medical University Fourth Hospital
Agency class:
Other
Collaborator:
Agency:
Handan Central Hospital
Agency class:
Other
Collaborator:
Agency:
Xingtai People's Hospital
Agency class:
Other
Source:
Hebei Medical University Fourth Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06103890
