Ignite Creation Date:
2025-12-25 @ 12:22 AM
Ignite Modification Date:
2025-12-25 @ 10:25 PM
Study NCT ID:
NCT03425058
Status:
COMPLETED
Last Update Posted:
2022-08-09
First Post:
2018-02-01
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Molecular Evaluation of Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer
Sponsor:
Peking University Cancer Hospital & Institute
Organization:
Study Overview
Official Title:
Prospective Study of Molecular Evaluation of Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer
Status:
COMPLETED
Status Verified Date:
2022-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MENCA-GC
Brief Summary:
Gastric cancer (GC) is a leading global health problem and is the third most common cause of cancer related death. Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced gastric cancer, and variable degrees of tumor regression are observed after nCRT. Treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of treatment response does not deliver an ideal accuracy of patients identification with complete response. In the present study, we focused on the clinical courses of patients who have developed locally advanced gastric cancer, and investigated the potential clinical utility of the detection of deficient MMR(dMMR), microsatellite instability(MSI) status and the decreasing level of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) as promising biomarkers for the diagnosis and prediction of GC during treatment progress. Twenty milliliters of plasma were collected at 3 time points: before nCRT; after 2 cycles of nCRT; and after surgery. Firefly ctDNA NGS assays were used to track ctDNA mutations previously characterized in paired tumor tissue by massively parallel sequencing (MPS). We investigated whether circulating tumor DNA (ctDNA) detection can reflect tumor response to nCRT and detect minimal residual disease(MRD) after surgery. We compared CTC and ctDNA levels to clinical, radiological and pathological assessment modalities for nCRT response. The results will provide lots of information which may contribute to promote the treatment of GC patients. We want to introduce these strategies into clinical practice if possible.
Detailed Description:
This study is a single-center observational study on a patient cohort of at least 80 patients with histologically-confirmed locally advanced gastric cancer (LAGC). The protocol used in this study is approved by the Ethics Committee of Beijing Cancer Hospital.
The primary endpoint is the 3-year progression-free survival (PFS) rate. The secondary endpoints are the overall survival (OS) and safety.
Currently, the best treatment for early and mid-stage LAGC patients is resection but even with successful treatment, most patients still relapse and the 5-year survival rate is less than 30%.
For patients with cT4a/T4bN+M0, including T4băBulky-N2, primary lesions are not always fully excised during treatment and prognosis for these patients is generally poor. Recent studies, however, have suggested that the inclusion of neoadjuvant chemotherapy (NCT) can improve patient outcomes by: 1) downstaging tumors and increasing the likelihood of curative resection, 2) reducing the prevalence of micro metastases.
Historically, Oxaliplatin and s-1 combination therapy has been shown to be well-tolerated in patients with recurrent or metastatic gastric cancer.
To best evaluate the treatment response of NCT, we plan to investigate the effect of new technologies and assays on the successful prediction of patient outcomes.
Circulating tumor DNA (ctDNA), fragmented DNA with an average size of 166 bp, is released by cancer cells into circulation. Circulating tumor cells (CTCs) are rare malignant cells detached from tumors which enter the bloodstream. Both these biomarkers can be used for prognosis and the dynamic monitoring of disease progression.
In the MAGIC trial, patients with tumor that are MSI-H or MMRD, had survival rates superior to those with MSS/MSI-L or MMRP tumors when treated with surgery alone.
We will combine dMMR/MSI status with the dynamic evaluation of CTCs and ctDNA using liquid biopsy technology to determine whether changes in tumor burden in response to NTC can identify potential treatment responders.
Sequential peripheral blood samples for CTCs and ctDNA analysis will be taken before and after NCT, as well as one week after surgery.
Tumor assessments will be performed after 2 cycles NCT based on RECIST v1.1 criteria using CT/MRI scan.
The primary endpoint is the 3-year progression-free survival (PFS) rate. The secondary endpoints are the overall survival (OS) and safety.
Currently, the best treatment for early and mid-stage LAGC patients is resection but even with successful treatment, most patients still relapse and the 5-year survival rate is less than 30%.
For patients with cT4a/T4bN+M0, including T4băBulky-N2, primary lesions are not always fully excised during treatment and prognosis for these patients is generally poor. Recent studies, however, have suggested that the inclusion of neoadjuvant chemotherapy (NCT) can improve patient outcomes by: 1) downstaging tumors and increasing the likelihood of curative resection, 2) reducing the prevalence of micro metastases.
Historically, Oxaliplatin and s-1 combination therapy has been shown to be well-tolerated in patients with recurrent or metastatic gastric cancer.
To best evaluate the treatment response of NCT, we plan to investigate the effect of new technologies and assays on the successful prediction of patient outcomes.
Circulating tumor DNA (ctDNA), fragmented DNA with an average size of 166 bp, is released by cancer cells into circulation. Circulating tumor cells (CTCs) are rare malignant cells detached from tumors which enter the bloodstream. Both these biomarkers can be used for prognosis and the dynamic monitoring of disease progression.
In the MAGIC trial, patients with tumor that are MSI-H or MMRD, had survival rates superior to those with MSS/MSI-L or MMRP tumors when treated with surgery alone.
We will combine dMMR/MSI status with the dynamic evaluation of CTCs and ctDNA using liquid biopsy technology to determine whether changes in tumor burden in response to NTC can identify potential treatment responders.
Sequential peripheral blood samples for CTCs and ctDNA analysis will be taken before and after NCT, as well as one week after surgery.
Tumor assessments will be performed after 2 cycles NCT based on RECIST v1.1 criteria using CT/MRI scan.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: