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出境医 / 临床实验 / Potential Clinical Utilities of Circulating Tumor DNA in Gastric Cancer

Potential Clinical Utilities of Circulating Tumor DNA in Gastric Cancer

Study Description
Brief Summary:
This study is designed to evaluate the potential clinical utility of ctDNA in the field of gastric cancer treatment,especially the usage of an indicator of MRD(minimal residual disease) in post radical gastrectomy patients. The primary purpose of this trial is to demonstrate if the postoperative ctDNA analysis could be used as an indicator of MRD or adjuvant chemotherapy response in advanced gastric cancer after radical gastrectomy.The second purpose is to describe the profile of ctDNA in gastric cancer.

Condition or disease Intervention/treatment
Gastric Cancer Combination Product: AVENIO ctDNA surveillance kit

Detailed Description:

Gastric cancer is an important health problem, being the fifth most common cancer and the third leading cause of cancer related death worldwide.Incidence shows clear regional and sex variations-rates are highest in Eastern Asia, Eastern Europe, and South America and lowest in Northern and Southern Africa. In China, gastric cancer accounts for nearly 16% of all malignant tumors and more than 80% of gastric cancer are in advanced stage.

Minimal residual disease (MRD) was proposed to describe the remaining tumor cells after treatment with curative intent. For curable gastric cancer, MRD means residential cancer cells after radical gastrectomy which share phenotypic similarity and genetic heritage with the original tumor. Treating MRD can increase the rates of cure had been supported by the experience of using adjuvant therapy for some type of solid tumor (for example, colorectal cancer, breast cancer). The challenge in monitoring the MRD in gastric cancer patients is that there is no very sensitive method. Computed tomography(CT) and blood tumor markers are either difficult to detect peritonial dissemination, the most frequent recurrent pattern in gastric caner or with limited sensitivity and specificity.

Tumor-specific DNA mutations detected in the cell-free component of peripheral blood, which is known as circulating tumor DNA (ctDNA), in most patients, allow for the noninvasive molecular characterization detection of tumors, including genetic changes that are revealed by the selective pressure of adjuvant therapies. Considering the origin of ctDNA, it can be from different subclones of primary tumor or both primary and metastatic tumors, the ctDNA may overcome the problems caused by tumor heterogeneity. Additionally, the short half-life of ctDNA, about 2 hours, makes ctDNA an ideal dynamic marker of tumor bulk.

In summary, the ctDNA is a good candidate to be a new kind of blood tumor marker. The preliminary studies had shown very good prospects in some tumors, including breast caner and colon cancer.But little was known in gastric cancer, so we designed this study to demonstrate the potential clinical utility of ctDNA in the field of gastric cancer treatment, especially the usage of an indicator of MRD in post radical gastrectomy patients.

Study Design
Layout table for study information
Study Type : Observational
Estimated Enrollment : 55 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Evaluating Potential Clinical Utilities of Circulating Tumor DNA in Gastric Cancer
Actual Study Start Date : December 1, 2018
Estimated Primary Completion Date : March 1, 2021
Estimated Study Completion Date : May 31, 2021
Arms and Interventions
Group/Cohort Intervention/treatment
ctDNA detection
The blood samples for ctDNA and other tumor markers (such as CEA, et al.) will be first collected within 7 days before surgery, and then be tested after radical gastrectomy in scheduled interval.
Combination Product: AVENIO ctDNA surveillance kit
AVENIO circulating tumor DNA (ctDNA) Analysis Kits is a portfolio of three next-generation sequencing (NGS) liquid biopsy assay kits for oncology research: the AVENIO ctDNA Targeted Kit, Expanded Kit and Surveillance Kit.

Outcome Measures
Primary Outcome Measures :
  1. Description of disease recurrence risk according to first positive ctDNA detection [ Time Frame: 2 years ]
    Time is measured from first positive ctDNA detection to disease-free survival event.

  2. Description of ctDNA changing to adjuvant chemotherapy response [ Time Frame: 2 years ]
    For subjects with postoperative positive ctDNA, time is measured from first adjuvant chemotherapy to first negative ctDNA detection.


Secondary Outcome Measures :
  1. Leading time between ctDNA detection and disease recurrence detected by conventional methods [ Time Frame: 2 years ]
    Time is measured between first positive ctDNA detection and first recurrence detected by conventional methods.

  2. The ctDNA level/mutations in gastric cancer preoperatively [ Time Frame: Within 7 days before operation ]
    Profiling of the most frequently detected gene mutations and level of mutations in preoperative ctDNA.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
Stomach adenocarcinoma patients who plan to receive radical gastrectomy and continuous circulating tumor DNA monitoring
Criteria

Inclusion Criteria:

  1. Male or female patients age 18 - 75.
  2. Eastern Cooperative Oncology Group (ECOG) performance status 0,1 or 2.
  3. Histologically proven primary stomach adenocarcinoma with Lauren type by gastroscopic biopsy before operation.
  4. Clinical stage is cT3/4N+M0 and the tumor is resectable in initial evaluation.
  5. No preoperative tumor therapy, including chemotherapy, radiotherapy, et al.
  6. No concomitant other malignant tumor or treated malignant tumor within last five years.
  7. Signed informed consent.
  8. Consent to provide research blood/tissue samples and clinicopathological information.

Exclusion Criteria:

  1. Radical gastrectomy was found cannot be achieved during operation due to metastasis or adjacent organ invasion.
  2. Only preoperative or postoperative blood sample was harvest or qualified.
  3. No qualified paired tissue samples.
  4. No complete clinicopatholoical information and follow-up.
  5. Presence of any systemic illness incompatible with participation in the clinical trial or inability to provide written informed consent.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Zhaoqing Tang, MD 86-21-64041990 tang.zhaoqing@zs-hospital.sh.cn

Locations
Layout table for location information
China, Shanghai
ZhongShan hospital FuDan university Recruiting
Shanghai, Shanghai, China, 200032
Contact: Zhaoqing Tang, MD       tang.zhaoqing@zs-hospital.sh.cn   
Sponsors and Collaborators
Shanghai Zhongshan Hospital
Investigators
Layout table for investigator information
Principal Investigator: Zhaoqing Tang, MD Fudan University
Tracking Information
First Submitted Date June 26, 2019
First Posted Date June 27, 2019
Last Update Posted Date June 27, 2019
Actual Study Start Date December 1, 2018
Estimated Primary Completion Date March 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 26, 2019)
  • Description of disease recurrence risk according to first positive ctDNA detection [ Time Frame: 2 years ]
    Time is measured from first positive ctDNA detection to disease-free survival event.
  • Description of ctDNA changing to adjuvant chemotherapy response [ Time Frame: 2 years ]
    For subjects with postoperative positive ctDNA, time is measured from first adjuvant chemotherapy to first negative ctDNA detection.
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: June 26, 2019)
  • Leading time between ctDNA detection and disease recurrence detected by conventional methods [ Time Frame: 2 years ]
    Time is measured between first positive ctDNA detection and first recurrence detected by conventional methods.
  • The ctDNA level/mutations in gastric cancer preoperatively [ Time Frame: Within 7 days before operation ]
    Profiling of the most frequently detected gene mutations and level of mutations in preoperative ctDNA.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Potential Clinical Utilities of Circulating Tumor DNA in Gastric Cancer
Official Title Evaluating Potential Clinical Utilities of Circulating Tumor DNA in Gastric Cancer
Brief Summary This study is designed to evaluate the potential clinical utility of ctDNA in the field of gastric cancer treatment,especially the usage of an indicator of MRD(minimal residual disease) in post radical gastrectomy patients. The primary purpose of this trial is to demonstrate if the postoperative ctDNA analysis could be used as an indicator of MRD or adjuvant chemotherapy response in advanced gastric cancer after radical gastrectomy.The second purpose is to describe the profile of ctDNA in gastric cancer.
Detailed Description

Gastric cancer is an important health problem, being the fifth most common cancer and the third leading cause of cancer related death worldwide.Incidence shows clear regional and sex variations-rates are highest in Eastern Asia, Eastern Europe, and South America and lowest in Northern and Southern Africa. In China, gastric cancer accounts for nearly 16% of all malignant tumors and more than 80% of gastric cancer are in advanced stage.

Minimal residual disease (MRD) was proposed to describe the remaining tumor cells after treatment with curative intent. For curable gastric cancer, MRD means residential cancer cells after radical gastrectomy which share phenotypic similarity and genetic heritage with the original tumor. Treating MRD can increase the rates of cure had been supported by the experience of using adjuvant therapy for some type of solid tumor (for example, colorectal cancer, breast cancer). The challenge in monitoring the MRD in gastric cancer patients is that there is no very sensitive method. Computed tomography(CT) and blood tumor markers are either difficult to detect peritonial dissemination, the most frequent recurrent pattern in gastric caner or with limited sensitivity and specificity.

Tumor-specific DNA mutations detected in the cell-free component of peripheral blood, which is known as circulating tumor DNA (ctDNA), in most patients, allow for the noninvasive molecular characterization detection of tumors, including genetic changes that are revealed by the selective pressure of adjuvant therapies. Considering the origin of ctDNA, it can be from different subclones of primary tumor or both primary and metastatic tumors, the ctDNA may overcome the problems caused by tumor heterogeneity. Additionally, the short half-life of ctDNA, about 2 hours, makes ctDNA an ideal dynamic marker of tumor bulk.

In summary, the ctDNA is a good candidate to be a new kind of blood tumor marker. The preliminary studies had shown very good prospects in some tumors, including breast caner and colon cancer.But little was known in gastric cancer, so we designed this study to demonstrate the potential clinical utility of ctDNA in the field of gastric cancer treatment, especially the usage of an indicator of MRD in post radical gastrectomy patients.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Stomach adenocarcinoma patients who plan to receive radical gastrectomy and continuous circulating tumor DNA monitoring
Condition Gastric Cancer
Intervention Combination Product: AVENIO ctDNA surveillance kit
AVENIO circulating tumor DNA (ctDNA) Analysis Kits is a portfolio of three next-generation sequencing (NGS) liquid biopsy assay kits for oncology research: the AVENIO ctDNA Targeted Kit, Expanded Kit and Surveillance Kit.
Study Groups/Cohorts ctDNA detection
The blood samples for ctDNA and other tumor markers (such as CEA, et al.) will be first collected within 7 days before surgery, and then be tested after radical gastrectomy in scheduled interval.
Intervention: Combination Product: AVENIO ctDNA surveillance kit
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Unknown status
Estimated Enrollment
 (submitted: June 26, 2019)
55
Original Estimated Enrollment Same as current
Estimated Study Completion Date May 31, 2021
Estimated Primary Completion Date March 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  1. Male or female patients age 18 - 75.
  2. Eastern Cooperative Oncology Group (ECOG) performance status 0,1 or 2.
  3. Histologically proven primary stomach adenocarcinoma with Lauren type by gastroscopic biopsy before operation.
  4. Clinical stage is cT3/4N+M0 and the tumor is resectable in initial evaluation.
  5. No preoperative tumor therapy, including chemotherapy, radiotherapy, et al.
  6. No concomitant other malignant tumor or treated malignant tumor within last five years.
  7. Signed informed consent.
  8. Consent to provide research blood/tissue samples and clinicopathological information.

Exclusion Criteria:

  1. Radical gastrectomy was found cannot be achieved during operation due to metastasis or adjacent organ invasion.
  2. Only preoperative or postoperative blood sample was harvest or qualified.
  3. No qualified paired tissue samples.
  4. No complete clinicopatholoical information and follow-up.
  5. Presence of any systemic illness incompatible with participation in the clinical trial or inability to provide written informed consent.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Not Provided
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries China
Removed Location Countries  
 
Administrative Information
NCT Number NCT04000425
Other Study ID Numbers ZSGC-005
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Shanghai Zhongshan Hospital
Study Sponsor Shanghai Zhongshan Hospital
Collaborators Not Provided
Investigators
Principal Investigator: Zhaoqing Tang, MD Fudan University
PRS Account Shanghai Zhongshan Hospital
Verification Date June 2019

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