Clinical Exploratory Study on Predicting Drug Sensitivity for Breast Cancer Treatment Using Simulated Organoid Models.

Recruiting

• Conditions: Breast Neoplasms

• Registration Number: NCT06702800
• Lead Sponsor: Xiangya Hospital of Central South University

Brief Summary

In this trial, we plan to construct a patient-derived organoid (PDO) model using fresh tumor tissue samples. Taking the relevant data of drug efficacy of breast cancer organoids as an example, it is shown that organoids may provide predictive information for drug sensitivity and may improve the therapeutic effect of advanced tumors. In this way, we aim to verify the effectiveness, feasibility and consistency of the PDO model in predicting treatment, and establish an evaluation system for treatment plans to help precision treatment of breast cancer.

Detailed Description

This study is a prospective, observational clinical research focusing on the drug sensitivity of patient-derived organoid (PDO) models, aiming to evaluate the consistency between the drug sensitivity of PDO models and the efficacy of selected clinical regimens.

1. Primary endpoint: The consistency between the drug sensitivity of the PDO model in analyzing treatment regimens and the objective response rate (ORR) of patients in clinical treatment.

2. Secondary endpoints: 1. To determine whether the PDO model can highly replicate the characteristics of the tumor microenvironment and maintain a high degree of consistency with tumor tissues in terms of molecules, cells, and tissue structures.

2. Based on the collection of drug sensitivity results of PDO and clinical treatment data, to comprehensively analyze the statistical differences in progression-free survival (PFS), overall survival (OS), and disease control rates (DCR) between patients whose clinical treatment regimens are consistent with the drug sensitivity results of PDO and those who are not.

(3) Exploratory endpoints: 1. To conduct peripheral blood mononuclear cell (PBMC) isolation tests and RNA sequencing (RNA seq) for the included subjects, analyze the potential reasons for the differences in the consistency of PDO's predicted efficacy, and explore the underlying mechanisms.

2. To evaluate the effectiveness of the organoid model in predicting the drug sensitivity of subsequent treatments for early refractory breast cancer patients, that is, to analyze the consistency between the drug sensitivity results detected by the organoid model and the pathological complete response rate (pCR) of patients who actually received subsequent treatments.

3. To assess the accuracy of the organoid model in predicting the drug sensitivity results of HER-2 positive breast cancer patients and their consistency with subsequent treatments.

4. To detect the expression of Trop-2 in triple-negative breast cancer (TNBC) organoids and the drug sensitivity test results of gossatumab, Dato-DXd, and SKB264 through immunohistochemistry and other techniques, and to determine whether they are consistent with the clinical treatment efficacy; whether the low expression of Trop-2 in breast cancer organoids is related to drug resistance in the source patients.

(III) Research Contents:

1. Screen breast cancer patients who meet the inclusion and exclusion criteria, perform puncture sampling for organoid model culture and preparation, and identify and verify whether the breast cancer organoids match the histological type of the original tumor.

2. Evaluate drug sensitivity using organoid model culture technology.

3. Conduct tumor assessment every 6 cycles, regularly perform safety visits and record, and explore the consistency between the drug sensitivity evaluated by the organoid model culture technology and the actual therapeutic effect of clinical patients, as well as the effectiveness and safety of this protocol.

3.1 Establishment of a PDO culture system suitable for breast cancer This study will use the hanging drop method organoid culture system, which can better preserve the tumor microenvironment of tumor cells, for the experiment. Breast cancer puncture samples obtained through informed consent will be digested into single-cell suspensions for organoid culture. Successfully cultured organoids will be collected for PBMC and RNA seq detection to assess the consistency of organoid tissue characteristics with those of the patient's pathological tissue and the infiltration of immune cells and drug penetration in the hanging drop method organoids. In this way, we will establish that the hanging drop method organoids reproduce the histological characteristics and marker expression of the original tumor tissue.

3.2 Detection of patient sensitivity to different induction chemotherapy regimens using the PDO system Based on the PDO organoid culture system established above, we will culture organoids from samples that meet the inclusion criteria. Once the culture is successful, the organoids will be immediately treated with multiple chemotherapy regimens and the treatment regimens that the patients will receive. The cell viability of the organoids will be measured as an indicator of organoid survival. By directly comparing with the CellTiter-Glo3D cell viability assay, the sensitivity of the organoids to different chemotherapy regimens will be statistically analyzed, and the most sensitive treatment regimen will be screened out.

3.3 Collection of clinical data and consistency analysis of drug sensitivity test results This trial aims to complete drug sensitivity tests on 30 samples. According to the actual clinical treatment regimens, the data of the 30 samples will be divided into two groups: consistent or inconsistent with the best drug sensitivity test regimen. The differences in objective response rate and disease control rate between the two groups will be statistically analyzed. At the same time, based on the drug sensitivity screening results, the consistency of clinical efficacy indicators of these patients will be statistically analyzed. In terms of prognosis, the differences in overall survival and progression-free survival between the two groups will be statistically analyzed.

Study Timeline

• Status Verified: 2024-06
• Study Start: 2024-06-01
• Study First Submitted: 2024-09-14
• Study First Submitted QC: 2024-11-21
• Study First Posted: 2024-11-25
• Last Update Submitted: 2025-02-26
• Last Update Posted: 2025-03-03
• Primary Completion: 2025-05-31
• Study Completion: 2026-05-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Objective Response Rate（ORR).	2024-06-02 to 2026-05-31	The proportion defined as subjects with complete remission (CR) and partial remission (PR) among all subjects.

Trial Locations

Locations (1)

Xiangya Hospital; 🇨🇳 Changsha, Hunan, China