Trial Title:
Research on the Correlation Between Organoid Drug Sensitivity Testing and Precise Treatment of Gastrointestinal Tumors
NCT ID:
NCT06332716
Condition:
Gastrointestinal Tumors,3D Organoids,Drug Sensitivity
Conditions: Official terms:
Digestive System Neoplasms
Gastrointestinal Neoplasms
Hypersensitivity
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Other
Intervention name:
Based on diagnostic and treatment guidelines/expert consensus, as well as clinical treatment experience, it is recommended that no more than 9 drugs be used for drug sensitivity testing each time.
Description:
Based on diagnostic and treatment guidelines/expert consensus, as well as clinical
treatment experience, it is recommended that no more than 9 drugs be used for drug
sensitivity testing each time. The sending doctor can choose from the following relevant
treatment drugs and confirm with the responsible researcher for drug sensitivity testing.
Arm group label:
Historical control group
Arm group label:
Treatment group based on organoid drug sensitivity testing
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.
1.1Participation Center Approximately 10-15 research centers are involved nationwide.
2.Case selection 2.1Selection 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 histopathology/cytology;
3. The subject's condition meets one of the following conditions:
Esophageal cancer: clinical staging is stage II (cT1-2N1-3M0/cT3-4NOMO) or stage III
(cT3-4aN1-3MO); Gastric cancer: Clinical staging is stage II (cT1-2N1-3M0/cT3-4N0MO)
or stage III (cT3-4aN1-3MO); Colorectal cancer: clinical staging is stage II
(cT1-2N1-3M0/cT3-4N0MO) or stage III (cT3-4aN1-3MO) Gastrointestinal stromal tumors:
Primary stromal tumors with locally advanced risk classification (spontaneous
rupture of the tumor; tumor diameter>10cm; mitotic image>10/5mm) ²; Tumor
diameter>5cm and mitotic count>5/5mm ²; 5cm ≤ tumor diameter>2cm and mitotic
image>5/5mm ² Non gastric primary; 10cm ≤ tumor diameter>5cm and mitotic image ≤
5/5mm ² (Non primary gastric stromal tumor) or recurrent metastatic/unresectable
gastrointestinal stromal tumor.
4. The patient or legal representative voluntarily participates in this study and signs
2.2 Exclusion criteria
One of the following situations cannot be included in this trial:
1. Suffering from systemic inflammatory diseases and/or 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 score<70 points, or ECOG score ≥ 3 points;
10. Receiving any other anti-cancer drug treatment, biological therapy, radiation
therapy, or immunosuppressive therapy within 4 weeks; 3.Research method
3.1Collection 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 ≥ 0.5g, 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
puncture/drainage: Total volume above 250ml, to avoid impurities and ensure the presence
of tumor cells.
3.2 Cold chain transportation The collected tumor samples should be stored on ice at 2-8
℃ for 24 hours and delivered to the laboratory.
3.3 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 M's 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 (organoid+drug
solvent); Positive control (organoid+astrosporin); Drug sensitivity testing group
(organoid+test 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 drug's 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 Evaluation/Luzhou 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.
3.4 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 guidelines/expert consensus, and clinical
experience of researchers.
The overall treatment plan for all subjects is formulated by the sub center researchers
based on their condition.
4.Research 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. 5.1Efficacy evaluation indicators
- Compare the differences between the organoid drug sensitivity results and the
recommended treatment plans based on guidelines/consensus; 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.
5.2 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 lesions>5mm. Calculation: Effective rate after treatment=(CR+PR)/total
number of cases x 100.0%; The objective response rate (OR) includes CR+PR
confirmed at least 4 weeks apart; The disease control rate (DCR) includes
confirmed tumor remission (CR+PR) and patients who have been recorded as SD
after at least 4 weeks of drug use, i.e. CR+PR+SD.
- 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients with esophageal cancer, gastric cancer, colorectal cancer, and
gastrointestinal stromal tumors confirmed by histopathology/cytology;
1. Esophageal cancer: clinical staging is stage II (cT1-2N1-3M0/cT3-4NOMO) or
stage III (cT3-4aN1-3MO);
2. Gastric cancer: Clinical staging is stage II (cT1-2N1-3M0/cT3-4N0MO) or stage
III (cT3-4aN1-3MO);
3. Colorectal cancer: clinical staging is stage II (cT1-2N1-3M0/cT3-4N0MO) or
stage III (cT3-4aN1-3MO)
4. Gastrointestinal stromal tumors: Primary stromal tumors with locally advanced
risk classification (tumor spontaneous rupture; tumor diameter>10cm; mitotic
image>10/50HPF; tumor diameter>5cm and mitotic image count>5/50HPF; 5cm ≤ tumor
diameter>2cm and mitotic image>5/50HPF non gastric primary stromal tumors; 10cm
≤ tumor diameter>5cm and mitotic image ≤ 5/50HPF non-gastric primary stromal
tumors) or recurrent metastatic/unresectable gastrointestinal stromal tumors.
2. The patient or legal representative voluntarily participates in this study and signs
an informed consent form.
Exclusion Criteria:
1. Suffering from systemic inflammatory diseases and/or 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 score<70 points, or ECOG score ≥ 3 points;
10. Receiving any other anti-cancer drug treatment, biological therapy, radiation
therapy, or immunosuppressive therapy within 4 weeks;
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
XijingH
Address:
City:
Xi'an
Country:
China
Status:
Recruiting
Contact:
Last name:
Jianjun Yang
Phone:
13756154175
Email:
yangjj@fmmu.edu.cn
Start date:
August 26, 2022
Completion date:
December 2025
Lead sponsor:
Agency:
Jianjun Yang,MD
Agency class:
Other
Source:
Xijing Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06332716