Ignite Creation Date:
2024-05-06 @ 4:40 PM
Last Modification Date:
2024-10-26 @ 2:14 PM
Study NCT ID:
NCT05051423
Status:
UNKNOWN
Last Update Posted:
2021-09-30
First Post:
2021-09-10
Brief Title:
Mechanisms and Biomarkers of Response and Resistance to Current Targeted Therapies in Gastric Cancer THERRES
Sponsor:
University of Medicine and Pharmacy Craiova
Organization:
University of Medicine and Pharmacy Craiova
Study Overview
Official Title:
Mechanisms and Biomarkers of Response and Resistance to Current Targeted Therapies in Gastric Cancer
Status:
UNKNOWN
Status Verified Date:
2021-09
Last Known Status:
RECRUITING
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:
THERRES
Brief Summary:
The main aim was to assess the tumor vascular perfusion pattern in gastric cancer GC The investigators used dynamic contrast harmonic imaging endoscopic ultrasound CHI-EUS and the results were compared with the immunohistochemical expression of CD105 and clinico-pathological parameters
Detailed Description:
The study design is prospective and will include patients with gastric tumors referred to Gastroenterology Department from University of Medicine and Pharmacy of Craiova for EUS local staging enrolled during 18 months
Data collected for each participant will include Personal data name surname age sex results from previous investigations blood count liver and renal function tests tumoral markers gastroscopy computed tomography EUS variables including CEH-EUS histological and immunohistochemical findings TNM and pTNM status if possible molecular analysis findings
Imaging tests All patients will be evaluated by EUS and CEH-EUS using radial EUS instruments Prior to the investigation the stomach has to be empty for at least 8 hours During the examination biopsies will be taken from normal and tumor tissue for gene expression analysis For EUS examination the patient will be placed in left lateral position The EUS scope will be inserted under direct vision passed by the tumor and examination should begin during withdrawal at 75 MHz The tumor will be characterized describing its echogenicity echostructure size extent into the wall and surrounding structures and it will be staged using the modification of the TNM classification The presenceabsence of power Doppler signals will be noted All lymph nodes will be reported with their maximal size echogenicity shape and margins Nodes larger than 5 mm in diameter with hypoechoic appearance round shape rather than ovoid or flat sharply demarcated borders and located nearby the tumor will be suspected for malignancy
CEH-EUS procedure A two panel image with the usual conventional gray-scale B-mode EUS image on the right side and with the contrast harmonic image on the left side will be used according to pre-established presets The examination will be performed at a low mechanical index dynamic wide-band contrast harmonic imaging mode of 02 The starting point of the timer will be considered the moment of intravenous contrast injection SonoVue 24 mL with the whole movie T0-T120s recorded on the embedded HDD of the ultrasound system for later analysis Parameters for objective measurement of tumor perfusion will include maximum intensity of enhancement mean transit time time to peak wash-in time wash-in slope area under the curve representing indirectly blood flow or blood volume in GC patients
Complications may occur during EUS but they are rare These consist of bleeding at the biopsy site which is usually minimal self-limited and rarely requires follow-up Perforation of the stomach is extremely rare The safety profile of the ultrasound contrast agent Sonovue showed a very low incidence of side effects It is not nephrotoxic and the incidence of hypersensitivity or severe allergic events is lower than with current X-ray agents and comparable to that of other magnetic resonance contrast agents Sono-Vue is approved for clinical use in EU countries
The biological material collected during the study will be frozen and stored This will include one ml of whole blood and 4 tissue biopsies 2 from normal tissue and 2 from the tumour of 2 to 3 mm each When the expected number of participants is reached the samples will undergo molecular studies for assessing the markers of angiogenesis as detailed further in the protocol The biological materials will be stored and analysed during an estimated time of 20 months from the start of the trial Biopsy samples for immunohistochemistry will be included in formalin solution and sent at pathology laboratory
Molecular tests
Blood analysis Whole blood 1ml will be collected before imaging procedures in an Eppendorf tube on EDTA solution placed immediately at 40C for maximum 24 hours and then kept at - 800C for later analysis of angiogenic factors
Biopsy samples of normal and GC tissue Gene expression will be analyzed using qPCR with Taqman- labeled probes To quantify the results obtained by real-time RT-PCR the standard curve method will be used The paired-samples will be collected in RNAlater Ambion stored at 40C for 12- 24 hours and then kept at - 800C Later analysis will assess the genes expression of angiogenic markers
Immunohistochemistry IHC will be focused of angiogenic markers VEGF-A family and their receptors VEGFR as well as tyrosine kinases receptors RTKs
The VEGF-C expression in tumor samples marker of lymphangiogenesis will be quantified Furthermore a correlation between EUS findings N stage and VEGF-C expression will be established
The microvessel density MVD will be calculated using immunohistochemistry for CD105
Statistical analysis The estimated number of participants enrolled to the study is at least 50 during first 24 months Both descriptive data analysis and statistical inference will be performed
Correlations between CE-EUS parameters and pathologic and genetic findings will be analyzed using the T-test and the Pearson correlation coefficient r for continuous data while the Chi-square test will be applied for categorical data One-way analysis of variance ANOVA will be performed for comparison between different subgroups T stages Survival analysis from the moment of diagnosis will be evaluated using Kaplan-Meyer curves Traditional parameters as TNM stage type of treatment will be analyzed Statistical significance will be defined as a p-value less than 005
These minimal risks will be outweighed by the potential implications for future patient care
Research subjects will receive consent on behalf of written and oral information before inclusion in the study The interview will cover detailed information including an understandable presentation of the project with its predictable risks and side-effects expected outcomes and benefits from the research
Any unplanned events or adverse effects will be reported immediately to the Regional Ethics Committee on biomedical research
Data collected for each participant will include Personal data name surname age sex results from previous investigations blood count liver and renal function tests tumoral markers gastroscopy computed tomography EUS variables including CEH-EUS histological and immunohistochemical findings TNM and pTNM status if possible molecular analysis findings
Imaging tests All patients will be evaluated by EUS and CEH-EUS using radial EUS instruments Prior to the investigation the stomach has to be empty for at least 8 hours During the examination biopsies will be taken from normal and tumor tissue for gene expression analysis For EUS examination the patient will be placed in left lateral position The EUS scope will be inserted under direct vision passed by the tumor and examination should begin during withdrawal at 75 MHz The tumor will be characterized describing its echogenicity echostructure size extent into the wall and surrounding structures and it will be staged using the modification of the TNM classification The presenceabsence of power Doppler signals will be noted All lymph nodes will be reported with their maximal size echogenicity shape and margins Nodes larger than 5 mm in diameter with hypoechoic appearance round shape rather than ovoid or flat sharply demarcated borders and located nearby the tumor will be suspected for malignancy
CEH-EUS procedure A two panel image with the usual conventional gray-scale B-mode EUS image on the right side and with the contrast harmonic image on the left side will be used according to pre-established presets The examination will be performed at a low mechanical index dynamic wide-band contrast harmonic imaging mode of 02 The starting point of the timer will be considered the moment of intravenous contrast injection SonoVue 24 mL with the whole movie T0-T120s recorded on the embedded HDD of the ultrasound system for later analysis Parameters for objective measurement of tumor perfusion will include maximum intensity of enhancement mean transit time time to peak wash-in time wash-in slope area under the curve representing indirectly blood flow or blood volume in GC patients
Complications may occur during EUS but they are rare These consist of bleeding at the biopsy site which is usually minimal self-limited and rarely requires follow-up Perforation of the stomach is extremely rare The safety profile of the ultrasound contrast agent Sonovue showed a very low incidence of side effects It is not nephrotoxic and the incidence of hypersensitivity or severe allergic events is lower than with current X-ray agents and comparable to that of other magnetic resonance contrast agents Sono-Vue is approved for clinical use in EU countries
The biological material collected during the study will be frozen and stored This will include one ml of whole blood and 4 tissue biopsies 2 from normal tissue and 2 from the tumour of 2 to 3 mm each When the expected number of participants is reached the samples will undergo molecular studies for assessing the markers of angiogenesis as detailed further in the protocol The biological materials will be stored and analysed during an estimated time of 20 months from the start of the trial Biopsy samples for immunohistochemistry will be included in formalin solution and sent at pathology laboratory
Molecular tests
Blood analysis Whole blood 1ml will be collected before imaging procedures in an Eppendorf tube on EDTA solution placed immediately at 40C for maximum 24 hours and then kept at - 800C for later analysis of angiogenic factors
Biopsy samples of normal and GC tissue Gene expression will be analyzed using qPCR with Taqman- labeled probes To quantify the results obtained by real-time RT-PCR the standard curve method will be used The paired-samples will be collected in RNAlater Ambion stored at 40C for 12- 24 hours and then kept at - 800C Later analysis will assess the genes expression of angiogenic markers
Immunohistochemistry IHC will be focused of angiogenic markers VEGF-A family and their receptors VEGFR as well as tyrosine kinases receptors RTKs
The VEGF-C expression in tumor samples marker of lymphangiogenesis will be quantified Furthermore a correlation between EUS findings N stage and VEGF-C expression will be established
The microvessel density MVD will be calculated using immunohistochemistry for CD105
Statistical analysis The estimated number of participants enrolled to the study is at least 50 during first 24 months Both descriptive data analysis and statistical inference will be performed
Correlations between CE-EUS parameters and pathologic and genetic findings will be analyzed using the T-test and the Pearson correlation coefficient r for continuous data while the Chi-square test will be applied for categorical data One-way analysis of variance ANOVA will be performed for comparison between different subgroups T stages Survival analysis from the moment of diagnosis will be evaluated using Kaplan-Meyer curves Traditional parameters as TNM stage type of treatment will be analyzed Statistical significance will be defined as a p-value less than 005
These minimal risks will be outweighed by the potential implications for future patient care
Research subjects will receive consent on behalf of written and oral information before inclusion in the study The interview will cover detailed information including an understandable presentation of the project with its predictable risks and side-effects expected outcomes and benefits from the research
Any unplanned events or adverse effects will be reported immediately to the Regional Ethics Committee on biomedical research
Study Oversight
Has Oversight DMC:
None
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?:
None