Patient-derived Organoid Drug Sensitivity Guided Treatment for Drug-resistant Recurrent Non-Small Cell Lung Cancer

Non-small Cell Lung Cancer Clinical Trial

Official title:

Patient-derived Organoid Drug Sensitivity Guided Treatment for Drug-resistant Recurrent Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06406608
• Other study ID #: 2024-107
• Status: Recruiting
• Phase: N/A
• Start date: April 16, 2024
• Est. completion date: June 16, 2026

Study information

• Verified date: April 2024
• Source: Henan Cancer Hospital
• Contact: Qiming Wang, PhD
• Phone: +8613783590691
• Email: qimingwang1006[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to enroll non-small cell lung cancer patients who have undergone at least two rounds of standard treatment for drug resistance/recurrence. Patient-derived Organoid will be established, and drug sensitivity test will be conducted to intervene in the selection of clinical treatment plans. Efficacy evaluation and prognosis analysis will also be conducted. It is hoped that this study will provide a basis for the development of personalized treatment plans.

Description:

Twenty patients with drug-resistant/relapsed non-small cell lung cancer who met the inclusion criteria were enrolled in the study after signing an informed consent form. Tumor samples were obtained through clinical puncture, and qualified samples were subjected to organoid modeling. Perform drug sensitivity test on the established lung cancer organoids. The drugs used are all that have been marketed and applied in clinical practice. According to the results of organoid drug sensitivity analysis, the patient received a treatment plan with relatively sensitive drugs. Follow up prognostic data and relevant clinical information of enrolled patients, conduct statistical analysis on the consistency between drug sensitivity test results and patient treatment response, and evaluate the clinical effectiveness of treatment plans guided by organoid drug sensitivity results.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: June 16, 2026
• Est. primary completion date: December 16, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age =18 and =75 years old (calculated based on the date of signing informed consent);

2. Diagnosed as drug-resistant/relapsed non-small cell lung cancer;

3. After at least two systemic treatments and the disease progresses;

4. According to the efficacy evaluation criteria of solid tumors (RECIST 1.1), at least one lesion that has not received radiation therapy, has not received other local therapies, and can obtain tumor tissue (can be from a single lesion source or multiple lesions combined) is used for organoid establishment;

5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-1;

6. Expected survival time>3 months;

7. Before a tumor sample can be taken, there must be a record of disease progression on imaging after the previous treatment.;

8. The patient has informed consent and signed a written consent form;

9. The patients had good compliance and willingly followed the study plan, including scheduled visits, treatments, laboratory tests, and other research steps.

Exclusion Criteria:

1. Extremely weakened overall condition, unable to tolerate bronchoscopy examination;

2. Patients with acute suppurative inflammation of the respiratory tract accompanied by high fever, acute asthma attacks, and ongoing hemoptysis;

3. Have a history of interstitial lung disease, non infectious pneumonia or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, etc

4. Patients with active leptomeningeal disease or brain metastasis;

5. Diagnosed with other malignant diseases other than NSCLC within 5 years prior to initial administration (excluding curative basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or curative resection of carcinoma in situ);

6. Have a history of immunodeficiency, including positive HIV serum tests;

7. Active hepatitis B without treatment (defined as HBsAg positive and HBV-DNA copy number detected is greater than the upper limit of normal value in the laboratory of the research center);

8. The presence of any serious or uncontrollable systemic diseases;

9. Pregnant or lactating female patients;

10. The researchers believe that patients who are not suitable to participate in this study.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Other:
• Chemotherapy and targeted-therapy guided by organoid drug sensitivity test
This study conducts drug sensitivity tests on various clinically approved drugs. The most sensitive drug for the patient is selected for treatment. This study aims to evaluate the clinical effectiveness of treatment plans guided by organoid drug sensitivity tests.

Locations

Country	Name	City	State
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (2)

Lead Sponsor	Collaborator
Henan Cancer Hospital	Kingbio Medical (Beijing) Co., Ltd.

Country where clinical trial is conducted

China, 

References & Publications (10)

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Drost J, Clevers H. Organoids in cancer research. Nat Rev Cancer. 2018 Jul;18(7):407-418. doi: 10.1038/s41568-018-0007-6. — View Citation

Kashima J, Kitadai R, Okuma Y. Molecular and Morphological Profiling of Lung Cancer: A Foundation for "Next-Generation" Pathologists and Oncologists. Cancers (Basel). 2019 Apr 29;11(5):599. doi: 10.3390/cancers11050599. — View Citation

Kim SY, Kim SM, Lim S, Lee JY, Choi SJ, Yang SD, Yun MR, Kim CG, Gu SR, Park C, Park AY, Lim SM, Heo SG, Kim H, Cho BC. Modeling Clinical Responses to Targeted Therapies by Patient-Derived Organoids of Advanced Lung Adenocarcinoma. Clin Cancer Res. 2021 Aug 1;27(15):4397-4409. doi: 10.1158/1078-0432.CCR-20-5026. Epub 2021 Jun 3. — View Citation

Li M, Izpisua Belmonte JC. Organoids - Preclinical Models of Human Disease. N Engl J Med. 2019 Feb 7;380(6):569-579. doi: 10.1056/NEJMra1806175. No abstract available. — View Citation

Muto S, Inomata S, Yamaguchi H, Mine H, Takagi H, Watanabe M, Ozaki Y, Inoue T, Yamaura T, Fukuhara M, Okabe N, Matsumura Y, Hasegawa T, Osugi J, Hoshino M, Higuchi M, Shio Y, Suzuki H. [Resistance Mechanisms to Immune Checkpoint Inhibitor and Its Overcome with Focus on beta-Catenin in Lung Cancer]. Gan To Kagaku Ryoho. 2022 Sep;49(9):928-931. Japanese. — View Citation

Romero-Calvo I, Weber CR, Ray M, Brown M, Kirby K, Nandi RK, Long TM, Sparrow SM, Ugolkov A, Qiang W, Zhang Y, Brunetti T, Kindler H, Segal JP, Rzhetsky A, Mazar AP, Buschmann MM, Weichselbaum R, Roggin K, White KP. Human Organoids Share Structural and Genetic Features with Primary Pancreatic Adenocarcinoma Tumors. Mol Cancer Res. 2019 Jan;17(1):70-83. doi: 10.1158/1541-7786.MCR-18-0531. Epub 2018 Aug 31. — View Citation

Seidlitz T, Merker SR, Rothe A, Zakrzewski F, von Neubeck C, Grutzmann K, Sommer U, Schweitzer C, Scholch S, Uhlemann H, Gaebler AM, Werner K, Krause M, Baretton GB, Welsch T, Koo BK, Aust DE, Klink B, Weitz J, Stange DE. Human gastric cancer modelling using organoids. Gut. 2019 Feb;68(2):207-217. doi: 10.1136/gutjnl-2017-314549. Epub 2018 Apr 27. — View Citation

Wang HM, Zhang CY, Peng KC, Chen ZX, Su JW, Li YF, Li WF, Gao QY, Zhang SL, Chen YQ, Zhou Q, Xu C, Xu CR, Wang Z, Su J, Yan HH, Zhang XC, Chen HJ, Wu YL, Yang JJ. Using patient-derived organoids to predict locally advanced or metastatic lung cancer tumor response: A real-world study. Cell Rep Med. 2023 Feb 21;4(2):100911. doi: 10.1016/j.xcrm.2022.100911. Epub 2023 Jan 18. — View Citation

Zhang Z, Yang S, Ma Y, Zhou H, Wu X, Han J, Hou J, Hao L, Spicer JD, Koh YW, Provencio M, Reguart N, Mitsudomi T, Wang Q. Consistency of recommendations for the diagnosis and treatment of non-small cell lung cancer: a systematic review. Transl Lung Cancer Res. 2021 Jun;10(6):2715-2732. doi: 10.21037/tlcr-21-423. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	Percentage of patient's measurable disease who have achieved either complete response (CR) or partial response (PR) according to RECIST 1.1.	1-2 years
Secondary	Progressive free survival	The time from initiation of treatment to the occurrence of disease progression or death.	1-2 years
Secondary	Overall survival time	The time from the date of randomization to the date of death for any cause. Patients will be followed until their date of death or until final database closure.	2 years