Ignite Creation Date:
2024-05-06 @ 8:18 PM
Last Modification Date:
2024-10-26 @ 3:25 PM
Study NCT ID:
NCT06332716
Status:
RECRUITING
Last Update Posted:
2024-03-27
First Post:
2024-03-13
Brief Title:
Research on the Correlation Between Organoid Drug Sensitivity Testing and Precise Treatment of Gastrointestinal Tumors
Sponsor:
Jianjun YangMD
Organization:
Xijing Hospital
Study Overview
Official Title:
Research on the Correlation Between Organoid Drug Sensitivity Testing and Precise Treatment of Gastrointestinal Tumors
Status:
RECRUITING
Status Verified Date:
2024-03
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:
None
Brief Summary:
Study the correlation between in vitro drug sensitivity screening of digestive tract tumor organoids and their clinical efficacy in anti-tumor treatment evaluate the use of digestive tract tumor organoid drug sensitivity to predict the therapeutic effect of anti-tumor drugs and explore new methods for personalized and precise treatment of esophageal cancer gastric cancer colorectal cancer and gastrointestinal stromal tumors
Detailed Description:
This trial is a single arm multicenter open label prospective clinical study
1 Sample size This study is a clinical exploratory study and does not estimate sample size It is expected to include 68 patients with digestive tract tumors including 16 cases each of esophageal cancer gastric cancer and colorectal cancer and 20 cases of gastrointestinal stromal tumors
11Participation Center Approximately 10-15 research centers are involved nationwide 2Case selection 21Selection criteria
To be selected all of the following conditions must be met
1 Age range from 18 to 75 years old regardless of gender
2 Patients with esophageal cancer gastric cancer colorectal cancer and gastrointestinal stromal tumors confirmed by histopathologycytology
3 The subjects condition meets one of the following conditions
Esophageal cancer clinical staging is stage II cT1-2N1-3M0cT3-4NOMO or stage III cT3-4aN1-3MO Gastric cancer Clinical staging is stage II cT1-2N1-3M0cT3-4N0MO or stage III cT3-4aN1-3MO Colorectal cancer clinical staging is stage II cT1-2N1-3M0cT3-4N0MO or stage III cT3-4aN1-3MO Gastrointestinal stromal tumors Primary stromal tumors with locally advanced risk classification spontaneous rupture of the tumor tumor diameter10cm mitotic image105mm ² Tumor diameter5cm and mitotic count55mm ² 5cm tumor diameter2cm and mitotic image55mm ² Non gastric primary 10cm tumor diameter5cm and mitotic image 55mm ² Non primary gastric stromal tumor or recurrent metastaticunresectable gastrointestinal stromal tumor
4 The patient or legal representative voluntarily participates in this study and signs 22 Exclusion criteria
One of the following situations cannot be included in this trial
1 Suffering from systemic inflammatory diseases andor coagulation disorders
2 There are serious liver and kidney diseases cardiovascular diseases respiratory diseases or uncontrolled diabetes
3 Suffering from other malignant tumors of the system
4 Patients with mental illness who are unable to cooperate in completing the study
5 Known allergies to potential chemotherapy drugs or surgical contraindications
6 Patients whose condition cannot be reversed or in a dying state
7 Unable to obtain sufficient tumor tissue through biopsy surgery for organoid culture and histological analysis
8 Pregnancy or lactation or planning to have a fertility plan within the next 6 months
9 Poor health status KPS score70 points or ECOG score 3 points
10 Receiving any other anti-cancer drug treatment biological therapy radiation therapy or immunosuppressive therapy within 4 weeks 3Research method 31Collection of Tumor Organ Samples Fresh tissue appropriate and sufficient sample size try to completely remove normal tissue to reduce interference
Endoscopic biopsy Take 3 or more pieces with forceps with a total amount of 05g and collect rich areas of cancer cells Puncture biopsy with a total length of 3cm each piece is 1cm or more a total of 3 pieces collect rich areas of cancer cells Ascites puncturedrainage Total volume above 250ml to avoid impurities and ensure the presence of tumor cells
32 Cold chain transportation The collected tumor samples should be stored on ice at 2-8 for 24 hours and delivered to the laboratory
33 Organ model drug sensitivity testing
1 Organoid culture I Obtaining Cell Suspension
① Tumor cell suspension After removing necrotic tissue adipose tissue and fibrous tissue from the sample the effective sample is cut into tumor tissue fragments with a diameter of 1mm and then the tissue fragments are digested using tissue dissociation solution Use 70-100 μ Ms sterile filter filters the digested tissue and the filtrate is centrifuged for 5 minutes before discarding the supernatant Use red blood cell lysase to lyse the red blood cells in the suspension centrifuge and suspend the precipitate using PBS
Malignant fluid cell suspension using 70-100 μ M sterile filter is used to filter malignant fluid remove solid suspension centrifuge and suspend the precipitate using PBS
II Cell viability verification Use trypan blue staining method to observe cell viability and ensure that the proportion of live cells is greater than 80
2 Establishment of organoids Spread the mixed matrix gel of tumor live cells evenly onto the pre prepared culture plate add suitable cell culture medium and then place it in a 37 5 CO ₂ incubator for static cultivation
3 Verification of organogenesis rate Pathological genetic testing and immunohistochemical validation are performed on samples of successfully cultured organoids to confirm the successful construction of tumor organoids If the validation is for normal tissue the sample fails and timely feedback is provided to the clinical sampling doctor
4 Sensitivity verification of organoid drugs After successful cultivation the organoids were divided into the following four groups zeroing group excluding organoids only containing cell culture medium Negative control organoiddrug solvent Positive control organoidastrosporin Drug sensitivity testing group organoidtest drug Each group has three wells and the selected drug for drug sensitivity testing is based on the recommendations of the researchers and the diagnosis and treatment guidelines of the Chinese Society of Clinical Oncology The clinical dose is used as the basis and three concentrations of high medium and low are set with a 3-fold gradient
5 Cell viability testing Cell viability was measured using ATP biofluorescence drug sensitivity detection technology ATP-TCA The complex of fluorescent pigment and fluorescent enzyme can undergo a chemical reaction with the participation of ATP to produce fluorescence The fluorescence intensity emitted reflects the content of ATP which in turn reflects the number of live cells ATP biofluorescence drug sensitivity detection technology uses intracellular ATP content as the endpoint for measuring cell activity which can measure the differences between different drugs and the same drug at different concentrations
6 Acquisition of drug sensitivity indicators Organ like growth inhibition rate The inhibition rate IR of different drug concentrations on organoids
Drug sensitivity assessment The drugs growth inhibition rate on organoids at clinical action concentration is used as a sensitivity indicator for tumor organoids to drugs An inhibition rate less than 20 indicates that organoids are resistant to the drug an inhibition rate of 20-40 indicates mild sensitivity an inhibition rate of 40-70 indicates moderate sensitivity and an inhibition rate greater than 70 indicates that organoids are highly sensitive to the drug
The above technical support is provided by a third-party professional technical platform Shanghai Biomass Drug EvaluationLuzhou Health Product Testing Center The time for issuing drug sensitivity results is about 2 weeks The drug sensitivity testing of gastrointestinal stromal tumors will be carried out based on the exploration results of the 3D culture method and agreed upon with the main unit of the project
34 Developing medication plans Construct a tumor organoid model based on biopsy specimens and develop a treatment plan based on organoid drug sensitivity results combined with diagnostic and treatment guidelinesexpert consensus and clinical experience of researchers
The overall treatment plan for all subjects is formulated by the sub center researchers based on their condition
4Research Procedures This study is divided into four parts screening period planning period treatment observation period and progression follow-up period
5 Efficacy evaluation After treatment evaluate and compare tumors of the same category 51Efficacy evaluation indicators
Compare the differences between the organoid drug sensitivity results and the recommended treatment plans based on guidelinesconsensus ② Changes in target lesions compared to baseline after 3 drug cycles of treatment chest and abdominal CT or MRI or PET-CT
Recurrence rate Based on patient follow-up information ④ Median progression free survival time and median survival time of patients combined with the cycle information of each tumor during patient follow-up
52 Criteria for determining efficacy
The efficacy is evaluated according to the World Health Organization WHO criteria for solid tumors
Complete response CR All target lesions disappear and the short axis values of all pathological lymph nodes are less than 10 mm
Partial response PR refers to the sum of the critical radius with a minimum reduction of 30 in the sum of all target lesion radii ③ Stable disease SD refers to the minimum value of the total observed target lesions which does not meet the progression criteria and also does not meet the remission criteria ④ Progressive disease PD The minimum value of the total observed target lesions the minimum increase of 20 in the total radius of all target lesions and the absolute value of the total increase in the radius of the target lesions5mm Calculation Effective rate after treatmentCRPRtotal number of cases x 1000 The objective response rate OR includes CRPR confirmed at least 4 weeks apart The disease control rate DCR includes confirmed tumor remission CRPR and patients who have been recorded as SD after at least 4 weeks of drug use ie CRPRSD
Tumor recurrence During imaging examination after treatment it was found that the tumor expanded again 6 months after partial remission and new tumors were found to recur in other parts or distant areas of the primary lesion After 6 months of complete remission tumor recurrence including local recurrence regional recurrence and distant recurrence was discovered through imaging examination
1 Sample size This study is a clinical exploratory study and does not estimate sample size It is expected to include 68 patients with digestive tract tumors including 16 cases each of esophageal cancer gastric cancer and colorectal cancer and 20 cases of gastrointestinal stromal tumors
11Participation Center Approximately 10-15 research centers are involved nationwide 2Case selection 21Selection criteria
To be selected all of the following conditions must be met
1 Age range from 18 to 75 years old regardless of gender
2 Patients with esophageal cancer gastric cancer colorectal cancer and gastrointestinal stromal tumors confirmed by histopathologycytology
3 The subjects condition meets one of the following conditions
Esophageal cancer clinical staging is stage II cT1-2N1-3M0cT3-4NOMO or stage III cT3-4aN1-3MO Gastric cancer Clinical staging is stage II cT1-2N1-3M0cT3-4N0MO or stage III cT3-4aN1-3MO Colorectal cancer clinical staging is stage II cT1-2N1-3M0cT3-4N0MO or stage III cT3-4aN1-3MO Gastrointestinal stromal tumors Primary stromal tumors with locally advanced risk classification spontaneous rupture of the tumor tumor diameter10cm mitotic image105mm ² Tumor diameter5cm and mitotic count55mm ² 5cm tumor diameter2cm and mitotic image55mm ² Non gastric primary 10cm tumor diameter5cm and mitotic image 55mm ² Non primary gastric stromal tumor or recurrent metastaticunresectable gastrointestinal stromal tumor
4 The patient or legal representative voluntarily participates in this study and signs 22 Exclusion criteria
One of the following situations cannot be included in this trial
1 Suffering from systemic inflammatory diseases andor coagulation disorders
2 There are serious liver and kidney diseases cardiovascular diseases respiratory diseases or uncontrolled diabetes
3 Suffering from other malignant tumors of the system
4 Patients with mental illness who are unable to cooperate in completing the study
5 Known allergies to potential chemotherapy drugs or surgical contraindications
6 Patients whose condition cannot be reversed or in a dying state
7 Unable to obtain sufficient tumor tissue through biopsy surgery for organoid culture and histological analysis
8 Pregnancy or lactation or planning to have a fertility plan within the next 6 months
9 Poor health status KPS score70 points or ECOG score 3 points
10 Receiving any other anti-cancer drug treatment biological therapy radiation therapy or immunosuppressive therapy within 4 weeks 3Research method 31Collection of Tumor Organ Samples Fresh tissue appropriate and sufficient sample size try to completely remove normal tissue to reduce interference
Endoscopic biopsy Take 3 or more pieces with forceps with a total amount of 05g and collect rich areas of cancer cells Puncture biopsy with a total length of 3cm each piece is 1cm or more a total of 3 pieces collect rich areas of cancer cells Ascites puncturedrainage Total volume above 250ml to avoid impurities and ensure the presence of tumor cells
32 Cold chain transportation The collected tumor samples should be stored on ice at 2-8 for 24 hours and delivered to the laboratory
33 Organ model drug sensitivity testing
1 Organoid culture I Obtaining Cell Suspension
① Tumor cell suspension After removing necrotic tissue adipose tissue and fibrous tissue from the sample the effective sample is cut into tumor tissue fragments with a diameter of 1mm and then the tissue fragments are digested using tissue dissociation solution Use 70-100 μ Ms sterile filter filters the digested tissue and the filtrate is centrifuged for 5 minutes before discarding the supernatant Use red blood cell lysase to lyse the red blood cells in the suspension centrifuge and suspend the precipitate using PBS
Malignant fluid cell suspension using 70-100 μ M sterile filter is used to filter malignant fluid remove solid suspension centrifuge and suspend the precipitate using PBS
II Cell viability verification Use trypan blue staining method to observe cell viability and ensure that the proportion of live cells is greater than 80
2 Establishment of organoids Spread the mixed matrix gel of tumor live cells evenly onto the pre prepared culture plate add suitable cell culture medium and then place it in a 37 5 CO ₂ incubator for static cultivation
3 Verification of organogenesis rate Pathological genetic testing and immunohistochemical validation are performed on samples of successfully cultured organoids to confirm the successful construction of tumor organoids If the validation is for normal tissue the sample fails and timely feedback is provided to the clinical sampling doctor
4 Sensitivity verification of organoid drugs After successful cultivation the organoids were divided into the following four groups zeroing group excluding organoids only containing cell culture medium Negative control organoiddrug solvent Positive control organoidastrosporin Drug sensitivity testing group organoidtest drug Each group has three wells and the selected drug for drug sensitivity testing is based on the recommendations of the researchers and the diagnosis and treatment guidelines of the Chinese Society of Clinical Oncology The clinical dose is used as the basis and three concentrations of high medium and low are set with a 3-fold gradient
5 Cell viability testing Cell viability was measured using ATP biofluorescence drug sensitivity detection technology ATP-TCA The complex of fluorescent pigment and fluorescent enzyme can undergo a chemical reaction with the participation of ATP to produce fluorescence The fluorescence intensity emitted reflects the content of ATP which in turn reflects the number of live cells ATP biofluorescence drug sensitivity detection technology uses intracellular ATP content as the endpoint for measuring cell activity which can measure the differences between different drugs and the same drug at different concentrations
6 Acquisition of drug sensitivity indicators Organ like growth inhibition rate The inhibition rate IR of different drug concentrations on organoids
Drug sensitivity assessment The drugs growth inhibition rate on organoids at clinical action concentration is used as a sensitivity indicator for tumor organoids to drugs An inhibition rate less than 20 indicates that organoids are resistant to the drug an inhibition rate of 20-40 indicates mild sensitivity an inhibition rate of 40-70 indicates moderate sensitivity and an inhibition rate greater than 70 indicates that organoids are highly sensitive to the drug
The above technical support is provided by a third-party professional technical platform Shanghai Biomass Drug EvaluationLuzhou Health Product Testing Center The time for issuing drug sensitivity results is about 2 weeks The drug sensitivity testing of gastrointestinal stromal tumors will be carried out based on the exploration results of the 3D culture method and agreed upon with the main unit of the project
34 Developing medication plans Construct a tumor organoid model based on biopsy specimens and develop a treatment plan based on organoid drug sensitivity results combined with diagnostic and treatment guidelinesexpert consensus and clinical experience of researchers
The overall treatment plan for all subjects is formulated by the sub center researchers based on their condition
4Research Procedures This study is divided into four parts screening period planning period treatment observation period and progression follow-up period
5 Efficacy evaluation After treatment evaluate and compare tumors of the same category 51Efficacy evaluation indicators
Compare the differences between the organoid drug sensitivity results and the recommended treatment plans based on guidelinesconsensus ② Changes in target lesions compared to baseline after 3 drug cycles of treatment chest and abdominal CT or MRI or PET-CT
Recurrence rate Based on patient follow-up information ④ Median progression free survival time and median survival time of patients combined with the cycle information of each tumor during patient follow-up
52 Criteria for determining efficacy
The efficacy is evaluated according to the World Health Organization WHO criteria for solid tumors
Complete response CR All target lesions disappear and the short axis values of all pathological lymph nodes are less than 10 mm
Partial response PR refers to the sum of the critical radius with a minimum reduction of 30 in the sum of all target lesion radii ③ Stable disease SD refers to the minimum value of the total observed target lesions which does not meet the progression criteria and also does not meet the remission criteria ④ Progressive disease PD The minimum value of the total observed target lesions the minimum increase of 20 in the total radius of all target lesions and the absolute value of the total increase in the radius of the target lesions5mm Calculation Effective rate after treatmentCRPRtotal number of cases x 1000 The objective response rate OR includes CRPR confirmed at least 4 weeks apart The disease control rate DCR includes confirmed tumor remission CRPR and patients who have been recorded as SD after at least 4 weeks of drug use ie CRPRSD
Tumor recurrence During imaging examination after treatment it was found that the tumor expanded again 6 months after partial remission and new tumors were found to recur in other parts or distant areas of the primary lesion After 6 months of complete remission tumor recurrence including local recurrence regional recurrence and distant recurrence was discovered through imaging examination
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?:
False
Is an FDA AA801 Violation?:
None