Evaluation of Consistency of PDX Model for Predicting Therapeutic Effect of Gastric Cancer

Recruiting

• Conditions: Precise Prediction of Therapy Efficiency
• Interventions: Other: biopsy of tumor before treatment

• Registration Number: NCT05616533
• Lead Sponsor: Zhejiang University

Brief Summary

The goal of this study is to compare the tumor response in gastric cancer patients given neoadjuvant chemotherapy with the corresponding result obtained from zebrafish patient-derived tumor xenograft(PDX) model given the same regimen. The main question it aims to answer is whether this PDX model of zebrafish could accurately predict the effect of chemotherapy in advanced gastric cancer. Participants will be given the standard neoadjuvant treatment administrated by their own doctors and tumor response will be observed and recorded. Meanwhile, tumor samples derived from patients before chemotherapy will be transplanted to zebrafish and the same regimen will be given to the PDX models correspondingly. The tumor response data both from clinical practice and PDX model platform will be analysed and compared to evaluate the power of this zebrafish model platform in drug efficiency prediction.

Detailed Description

The prognosis of advanced gastric cancer treated with surgery only remains quite disappointed. Adjuvant and neoadjuvant chemotherapy had been greatly raising the survive of advanced gastric cancer. However, how to acquired the tumor sensitivity to the following chemotherapy before the treatment, in order to admit reasonable drugs, avoid unexpected progression of tumor and unnecessary loss of surgical opportunity, remained the focus in this field. Zebrafish CDX/PDX model provides a reliable potential platform for drug sensitivity prediction, but the drug sensitivity result concluded by this platform could not fully represent its actual clinic efficacy in human body. Consistency of therapeutic efficacy could be concluded only by comparing the results both in the human body and the model that was given the same regimens. This is the golden standard to evaluate whether the PDX model of zebrafish could accurately predict the effect of chemotherapy, as well as the primary foundation of the clinical practice with this zebrafish model platform for drug efficiency prediction. Therefore, we intend to carry out this clinical study in gastric cancer patients whom were given neoadjuvant chemotherapy. Enrolled individuals was given a biopsy through endoscopy to obtain samples that would be transplanted to the zebrafish model. Same drugs would be give both for the patient and corresponding zebrafish model, and results would be observed carefully to assess the consistency between the model and the actual practice. This may give strong support for the future clinical use of the platform.

Study Timeline

• Study First Submitted: 2022-11-07
• Study First Submitted QC: 2022-11-13
• Study First Posted: 2022-11-15
• Study Start: 2023-09-12
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-22
• Last Update Posted: 2023-12-26
• Primary Completion: 2024-09-30
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. patients aged 18-75years,
2. patients with gastric cancer confirmed by histology or cytology at first visit,
3. patients with advanced tumor by imaging evaluation,
4. patients with preoperative neoadjuvant therapy;
5. Eastern Cooperative Oncology Group (ECOG) physical status score of 0 or 1;
6. tolerance to chemotherapy in laboratory examination;
7. hematology examination: no obvious signs of hematological diseases, ANC ≥1.5 × 109/L before enrollment; Platelet count ≥80 × 109/L, HB ≥90 g/L, WBC ≥3.0 × 109/L, and no bleeding tendency;
8. biochemical examination: Total Bilirubin <1.5 times of upper limit of normal value, AST, ALT < 2.5 times of upper limit of normal value, creatinine < 1.5 times of upper limit of normal value;

Exclusion Criteria

1. patients with inoperable advanced gastric cancer,
2. patients with metastatic or primary gastric cancer,
3. pregnant or lactating women,
4. patients with a history of other malignancies in the last 5 years;
5. for those with a history of uncontrolled epilepsy, central nervous system disease or mental disorders, the severity of the clinical condition was assessed by the investigator as impeding the signing of informed consent or affecting the patient's compliance with oral medication;
6. clinically serious (i.e. active) heart disease, such as symptomatic coronary heart disease, NYHA Class II or more heart failure, or arrhythmias requiring medical intervention; Or a history of myocardial infarction within the last 12 months;
7. severe diabetes-related complications, such as diabetic nephropathy, diabetic ketosis, etc.
8. gastrointestinal obstruction or abnormal physiological function, or malabsorption syndrome, which may affect drug absorption;
9. gastrointestinal bleeding in the last two weeks or at high risk of bleeding as judged by the investigator;
10. patients with known peripheral nerve disease ≥ NCI-CTC AE Grade 1, but only with deep tendon reflexes (DTR) ;
11. organ transplantation requires immunosuppressive therapy;
12. the presence of any active, known or suspected autoimmune disease.
13. uncontrolled severe infection or other severe concomitant disease
14. hypersensitivity to paclitaxel, Oxaliplatin, 5-FU, or any clinically useful anti-gastric cancer agent.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
focused group	biopsy of tumor before treatment	Advanced gastric patients that will be treated with neoadjuvant therapy are enrolled. Every clinical decision such as regimen or dosage will be decided by their own doctors without any interventions. Tumor samples will be obtained before the first cycle of the treatment and will be transplanted to the zebrafish model. Compared results will be analyzed in future.

Primary Outcome Measures

Name	Time	Method
The coincidence rate of tumor response obtained from 50 PDX models with clinical real tumor response acquired from corresponding patients received neoadjuvant therapy.	about 3 months (from the first cycle of neoadjuvant therapy to the surgery)	Drugs used in the zebrafish PDX model are as same as those administrated in the clinical practice with the corresponding patient. Immunofluorescence quantitative detection would be used to evaluate the tumor response in PDX model while RECIST 1.1 and Becker criterion would be applied to evaluate the real tumor response in clinical practice.

Trial Locations

Locations (1)

gastrointestinal department of second affiliated hospital of Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China