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Organoids Predict Therapeutic Response in Patients With Multi-line Drug-resistant Non-small Cell Lung Cancer

Primary Purpose

Lung Cancer, Organoid, NSCLC

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Antitumor therapy guided by organoid drug sensitivity test
Sponsored by
Affiliated Hospital of Jiangnan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Male or female patients: ≥18 years old. For non-small cell lung cancer confirmed by histology or cytology, there is no standard protocol recommendation in the guidelines for disease progression after multiline standard therapy. Expected survival ≥3 months. Sign informed consent. The patient is willing and able to adhere to the protocol during the study, including receiving treatment and scheduled visits and examinations, including follow-up. Accessible to biopsy and/or surgery sample of metastasis and/or primitive tumour At least one previously unirradiated lesion that can be accurately measured at baseline with longest diameter ≥ 10 mm (must have a short lymph node excluding axis ≥ 15 mm) according to RECIST criteria with computed tomography (CT), magnetic resonance imaging (MRI) or clinical examination for accurate repeated measures. Or an unevaluable lesion, including but not limited to pleural and ascites, bone metastasis, etc. Exclusion Criteria: Participated in clinical trials of other drugs within four weeks. Histologically or cytologically confirmed small cell, large cell neuroendocrine or carcinoid. Not accessible to biopsy and/or surgery sample. Not enough lung tissue for a histological analysis or the remaining lung tissue is not enough to perform a routine pathological analysis. There are clinical symptoms or diseases of the heart that cannot be well controlled, such as: NYHA class 2 or higher heart failure, unstable angina pectoris, myocardial infarction within 1 year, clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention of patients. For female subjects: should be surgically sterilized, postmenopausal patients, or agree to use a medically approved contraceptive during the study treatment period and within 6 months after the end of the study treatment period; Serum or urine pregnancy test must be negative within 7 days and must be non-nursing. Male subjects: Patients who should be surgically sterilized, or who agree to use a medically-approved contraceptive method during the study treatment period and within 6 months after the end of the study treatment period. The patient has active pulmonary tuberculosis, bacterial or fungal infection (≥ grade 2 of NCI-CTC, 3rd edition); HIV infection, HBV infection, HCV infection. Those who have a history of psychotropic substance abuse and cannot quit or have mental disorders. The subject has any active autoimmune disease or has a history of autoimmune disease (such as the following, but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, thyroid Reduced function; subjects with vitiligo or complete remission of asthma in childhood without any intervention in adulthood can be included; subjects with asthma requiring bronchodilator medical intervention are not included). According to the judgment of the investigator, there are concomitant diseases that seriously endanger the patient's safety or affect the patient's completion of the study.

Sites / Locations

  • Affiliated Hospital of Jiangnan UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Organoid-Guided Antitumor therapy

Physician-decided Antitumor therapy

Arm Description

Non-small cell lung cancer specimens are obtained from lung tumor surgery or biopsy and are used to grow organoids. Then organoids are used for drug sensitivity tests to obtain the sensitivity to drugs. Patients will receive a relatively sensitive antitumor regimen based on the test results.

According to the National Comprehensive Cancer Network's (NCCN) Guidelines for non-small cell lung Cancer, physicians will determine antitumor protocols. They're also not sure what the drug susceptibility test says.

Outcomes

Primary Outcome Measures

Progression-free survival
Time from randomization to any disease progression and/or death, defined according to strict RECIST (Response Evaluation Criteria in Solid Tumors) v1.1. Lesion will be assessed in comparison to baseline measurements.

Secondary Outcome Measures

Overall survival
Randomize time to date of death or last known alive date calculation.
Disease control rate
The proportion of patients with a best response grade of complete response, partial response, or stable disease that has shrunk or stabilized for a period of time.
Changes in tumor volume shrinking
Change in tumor volume reduction from randomization to 6 months
Prediction of the response to treatment by the patient-derived organoids
The drug sensitivity was tested on patient-derived tumour organoids, which is compared with clinical response of the chemo- or targeted therapy treatment.
The rate of successful generation of lung cancer organoids
Successful generation of lung cancer organoids (growth of lung tumoral cells).

Full Information

First Posted
December 20, 2022
Last Updated
February 2, 2023
Sponsor
Affiliated Hospital of Jiangnan University
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1. Study Identification

Unique Protocol Identification Number
NCT05669586
Brief Title
Organoids Predict Therapeutic Response in Patients With Multi-line Drug-resistant Non-small Cell Lung Cancer
Official Title
A Single-arm, Single-center Clinical Trial of Patient-derived Lung Cancer Organoids for Predicting Therapeutic Response in Patients With Multiline Drug-resistant Non-small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2023 (Actual)
Primary Completion Date
May 31, 2024 (Anticipated)
Study Completion Date
May 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Affiliated Hospital of Jiangnan University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is a single-center, single-arm, open and exploratory clinical study. The purpose of this study was to evaluate the consistency and accuracy of the organogenic (PDO) model for patients with lung cancer, to predict the clinical efficacy of anticancer drugs, and to speculate and select personalized treatment regiments for patients with non-small cell lung cancer who are resistant to multi-line standard therapies.
Detailed Description
As for the difficult problem of drug resistance in NSCLC after multi-line therapy, there is no standard consensus in clinical diagnosis and treatment, and relevant treatment plans are still being explored and the efficacy is unknown. Patient-derived organoid cells (PDOs) have become a reliable tumor model for drugs in vitro. PDOs is a personalized tumor model with similar characteristics to the original tumor. This model can maintain the molecular and cellular composition of the original tumor, reflect the heterogeneity of the original tumor, and realize in vitro high-throughput rapid screening of drug sensitivity, accurately predict the drug response of patients, so as to provide rapid clinical drug feedback. In recent years, lung cancer organoids have also been rapidly established to reproduce the tissue structure of primary lung tumors, screen the sensitivity of therapeutic drugs, formulate lung cancer treatment programs, and realize individualized tumor treatment of lung cancer. Patients were highly matched to their PDO responses, with 84.43% accuracy, 78.01% sensitivity and 91.97% specificity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer, Organoid, NSCLC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Organoid-Guided Antitumor therapy
Arm Type
Experimental
Arm Description
Non-small cell lung cancer specimens are obtained from lung tumor surgery or biopsy and are used to grow organoids. Then organoids are used for drug sensitivity tests to obtain the sensitivity to drugs. Patients will receive a relatively sensitive antitumor regimen based on the test results.
Arm Title
Physician-decided Antitumor therapy
Arm Type
No Intervention
Arm Description
According to the National Comprehensive Cancer Network's (NCCN) Guidelines for non-small cell lung Cancer, physicians will determine antitumor protocols. They're also not sure what the drug susceptibility test says.
Intervention Type
Drug
Intervention Name(s)
Antitumor therapy guided by organoid drug sensitivity test
Intervention Description
Antitumor therapy guided by organoid will be given to Multi-line Drug-resistant Non-small Cell Lung Cancer patients.
Primary Outcome Measure Information:
Title
Progression-free survival
Description
Time from randomization to any disease progression and/or death, defined according to strict RECIST (Response Evaluation Criteria in Solid Tumors) v1.1. Lesion will be assessed in comparison to baseline measurements.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Overall survival
Description
Randomize time to date of death or last known alive date calculation.
Time Frame
72 weeks
Title
Disease control rate
Description
The proportion of patients with a best response grade of complete response, partial response, or stable disease that has shrunk or stabilized for a period of time.
Time Frame
an average of 1 year
Title
Changes in tumor volume shrinking
Description
Change in tumor volume reduction from randomization to 6 months
Time Frame
6 months
Title
Prediction of the response to treatment by the patient-derived organoids
Description
The drug sensitivity was tested on patient-derived tumour organoids, which is compared with clinical response of the chemo- or targeted therapy treatment.
Time Frame
2 years
Title
The rate of successful generation of lung cancer organoids
Description
Successful generation of lung cancer organoids (growth of lung tumoral cells).
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female patients: ≥18 years old. For non-small cell lung cancer confirmed by histology or cytology, there is no standard protocol recommendation in the guidelines for disease progression after multiline standard therapy. Expected survival ≥3 months. Sign informed consent. The patient is willing and able to adhere to the protocol during the study, including receiving treatment and scheduled visits and examinations, including follow-up. Accessible to biopsy and/or surgery sample of metastasis and/or primitive tumour At least one previously unirradiated lesion that can be accurately measured at baseline with longest diameter ≥ 10 mm (must have a short lymph node excluding axis ≥ 15 mm) according to RECIST criteria with computed tomography (CT), magnetic resonance imaging (MRI) or clinical examination for accurate repeated measures. Or an unevaluable lesion, including but not limited to pleural and ascites, bone metastasis, etc. Exclusion Criteria: Participated in clinical trials of other drugs within four weeks. Histologically or cytologically confirmed small cell, large cell neuroendocrine or carcinoid. Not accessible to biopsy and/or surgery sample. Not enough lung tissue for a histological analysis or the remaining lung tissue is not enough to perform a routine pathological analysis. There are clinical symptoms or diseases of the heart that cannot be well controlled, such as: NYHA class 2 or higher heart failure, unstable angina pectoris, myocardial infarction within 1 year, clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention of patients. For female subjects: should be surgically sterilized, postmenopausal patients, or agree to use a medically approved contraceptive during the study treatment period and within 6 months after the end of the study treatment period; Serum or urine pregnancy test must be negative within 7 days and must be non-nursing. Male subjects: Patients who should be surgically sterilized, or who agree to use a medically-approved contraceptive method during the study treatment period and within 6 months after the end of the study treatment period. The patient has active pulmonary tuberculosis, bacterial or fungal infection (≥ grade 2 of NCI-CTC, 3rd edition); HIV infection, HBV infection, HCV infection. Those who have a history of psychotropic substance abuse and cannot quit or have mental disorders. The subject has any active autoimmune disease or has a history of autoimmune disease (such as the following, but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, thyroid Reduced function; subjects with vitiligo or complete remission of asthma in childhood without any intervention in adulthood can be included; subjects with asthma requiring bronchodilator medical intervention are not included). According to the judgment of the investigator, there are concomitant diseases that seriously endanger the patient's safety or affect the patient's completion of the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
quan liu, doctor
Phone
15995299079
Email
quanliu@jiangnan.edu.cn; quanliu.lq@outlook.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
quan liu, doctor
Organizational Affiliation
Affiliated Hospital of Jiangnan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Affiliated Hospital of Jiangnan University
City
Wuxi
State/Province
Jiangsu
ZIP/Postal Code
214000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
liu quan, doctor
Phone
15995299079
Email
quanliu@jiangnan.edu.cn; quanliu.lq@outlook.com
First Name & Middle Initial & Last Name & Degree
liu quan, doctor

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Organoids Predict Therapeutic Response in Patients With Multi-line Drug-resistant Non-small Cell Lung Cancer

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