Gastric Cancer Organoids in the Screening of Neoadjuvant Drugs

December 25, 2023 updated by: Dong Bing Zhao

Exploratory Study of Gastric Cancer Organoids in the Screening of Neoadjuvant Chemotherapy and Immunotherapy Drugs

Gastric cancer is an important disease burden that threatens human health. Due to the complex biological characteristics of gastric cancer, the research on gastric cancer is still at a low level. Organoid technology is a breakthrough technology in cancer research. Gastric cancer organoid is a good model for gastric cancer research by three-dimensional culture of tumor cells in vitro, which simulates the spatial morphology and structure of tumors in vivo while preserving the biological characteristics of tumor cells. At present, gastric cancer organoid models have shown great advantages in many fields, such as the mechanism of gastric cancer development, tumor drug resistance, large-throughput chemotherapy drug screening, novel therapeutic target searching, and preclinical validation of novel drugs.

In the current clinical trial, investigators cultured organoids from gastroscopic biopsy tissue of gastric cancer patients, and compared the organoids with the sampled tumors, including immunohistochemical indicators (Ki67+/CK20+/CDX2+), WES sequencing results. At the same time according to the guidelines. The recommended treatment plan is to compare the organoid model drug screening results with the clinical drug sensitivity.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

There is an important clinical problem in neoadjuvant chemotherapy, adjuvant chemotherapy and palliative chemotherapy for locally advanced gastric cancer, that is, insufficient effectiveness of chemotherapy. Among the patients with neoadjuvant therapy, some patients will have pathological complete remission, and the prognosis of these patients is better than that of other patients.

However, not all patients have a good pathological response after neoadjuvant chemotherapy, although many studies have reported uneven response rates and individual differences in patient sensitivity to chemotherapy drugs. At present, investigators still lack adequate methods to predict the effectiveness of chemotherapy and adjust treatment strategies in time to achieve the best clinical outcomes.

In addition, targeted therapy and immunotherapy are widely used in clinical practice, and gene sequencing is performed on tumor samples of patients to guide the selection of targeted drugs. However, according to clinical data feedback, this method has many limitations, for example, patients with a targeted gene mutation of a targeted drug cannot respond to the drug, while patients without the targeted gene mutation can respond very well to the drug. The reason is that the sequencing results based on some known proto-oncogenes or tumor suppressor genes cannot fully reflect the genomic background of the patient, including some unknown cancer-related genes, and even non-coding protein sequences play important regulatory roles in the process of cancer. Therefore, how to quickly select the most effective drug for this patient among the numerous cancer targeted drugs on the market is the decisive factor for the success or failure of cancer precision medicine.

In recent years, an important breakthrough in basic tumor research is the tumor organoid technology established in vitro, which directly obtains tumor tissue from patients, rapidly expands in vitro, and forms organoids with a high physiological and pathological state similar to the original tissue in a short time. This organoid is a three-dimensional assembly of cells containing more than one cell type. Since the cultured organoids are derived from the patient's own tumor tissue, they can well retain various characteristics of the tumor tissue in situ. Compared with the traditional 2D cell line culture, organoids are directly derived from patients, can retain the patient's genomic information and epigenetic information, maintain the heterogeneous components of the original tumor, and have a 3D structure that is more in line with the conditions in vivo, so it is more representative. Compared with the animal transplant tumor model derived from patients, organoids have the advantages of low cost, high success rate, short culture cycle and easy operation. In general, tumor organoids combine the advantages of 2D cell line culture and animal transplant tumor models, which can not only fully reflect the genetic information and tumor phenotype of patients, but also ensure the heterogeneity of tumors, and have high economic benefits. Therefore, they are favored in scientific research and clinical practice, and are effective tools for evaluating drug response and screening drugs. There are already some of the top cancer research institutes in the world, National Cancer Institute (Netherlands), Cancer Research UK (UK) and the Wellcome Trust Sanger Institute (UK) are working together to build a sample bank of various Tumor organoids that are already being used in precision medicine for cancer patients.

As such, investigators designed a single-center prospective, observational clinical trial for patients with locally advanced gastric cancer, aiming to explore the application of gastric cancer organoids in chemotherapy drug screening, so as to improve the efficacy of neoadjuvant chemotherapy for gastric cancer and provide a basis for the precision treatment of neoadjuvant therapy for gastric cancer.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
      • Beijing, China, 100021
        • Recruiting
        • Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/ National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Probability Sample

Study Population

The study population was patients with locally advanced gastric cancer receiving neoadjuvant chemotherapy.

Description

Inclusion Criteria:

  • 1: The patients voluntarily participated in this study and signed the informed consent;
  • 2: 18 to 80 years old.
  • 3: American Society of Anesthesiologists (ASA) score ≤3 (no risk of anesthesia during surgery).
  • 4: Patients diagnosed with gastric cancer by pathological examination.
  • 5: Expected survival is greater than 6 months.
  • 6: Blood routine: Hb≥70g/L, WBC≥3.5×109/L, ANC≥1.5×109/L, PLT≥80×109/L.
  • 7: Serum ALT and AST≤2×ULN; Serum creatinine≤1.5×ULN.
  • 8: Women of childbearing age must undergo a pregnancy test (serum or urine) within 7 days before enrollment, and the result is negative, and they are willing to use appropriate methods of contraception during the trial.
  • 9: According to the judgment of the investigator, patients who can comply with the protocol.
  • 10: Patients with locally advanced gastric cancer requiring neoadjuvant therapy.

Exclusion Criteria:

  • 1: Active or uncontrolled serious infection.
  • 2: Liver cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis require antiviral treatment.
  • 3: A history of immunodeficiency, including HIV positive or other acquired congenital immunodeficiency diseases.
  • 4: Chronic renal insufficiency and renal failure.
  • 5: Patients who have suffered from or combined with other malignant tumors.
  • 6: Myocardial infarction, severe arrhythmia and ≥ grade 2 congestive heart failure (New York Heart Association (NYHA) classification).
  • 7: Patients with autoimmune diseases such as systemic lupus erythematosus.
  • 8: Complications, need to take drugs with serious liver and kidney damage during treatment, such as tuberculosis.
  • 9: Patients who cannot understand the content of the experiment and cannot cooperate and those who refuse to sign the informed consent.
  • 10: Those with concomitant diseases or other special circumstances that seriously endanger the safety of patients or affect the completion of the study.
  • 11: Combined with neoadjuvant radiotherapy.
  • 12: Postoperative follow-up was not completed.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Predictive sensitivity of drug sensitivity
Time Frame: At the end of Cycle 2 (each cycle is 21 days); At the end of Cycle 4 (each cycle is 21 days); Ten days after surgery;
Consistency ratio between organoid drug screening results and actual clinical observation drug sensitivity.
At the end of Cycle 2 (each cycle is 21 days); At the end of Cycle 4 (each cycle is 21 days); Ten days after surgery;
Predictive specificity of drug sensitivity
Time Frame: At the end of Cycle 2 (each cycle is 21 days); At the end of Cycle 4 (each cycle is 21 days); Ten days after surgery;
The proportion of inconsistencies between organoid drug screening results and actual clinical observation drug sensitivity.
At the end of Cycle 2 (each cycle is 21 days); At the end of Cycle 4 (each cycle is 21 days); Ten days after surgery;

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Concordance between organoids and source tumor tissue
Time Frame: Organoid models were established and compared after passaging 3-5 generations (Three weeks)
Concordance between organoids and source tumor tissue
Organoid models were established and compared after passaging 3-5 generations (Three weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Dong Bing Zhao

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Dongbing Zhao, MD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 28, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 28, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 1, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 25, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 9, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 9, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 25, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Cancer Institute and Hospital,

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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