Clinical trial NCT05669586: Organoids Predict Therapeutic Response in Patients With Multi-line Drug-resistant 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 Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Lung Cancer
Organoid
Lead sponsor: Affiliated Hospital of Jiangnan University
Sponsor class: OTHER
First posted: 2023-01-03
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 lung cancer who are resistant to multi-line standard therapies.

Detailed description: As for the difficult problem of drug resistance in lung cancer 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female patients: ≥18 years old.
2. 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.
3. Expected survival ≥3 months.
4. Sign informed consent.
5. 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.
6. Accessible to biopsy and/or surgery sample of metastasis and/or primitive tumour
7. 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:

1. Participated in clinical trials of other drugs within four weeks.
2. Histologically or cytologically confirmed small cell, large cell neuroendocrine or carcinoid.
3. Not accessible to biopsy and/or surgery sample.
4. Not enough lung tissue for a histological analysis or the remaining lung tissue is not enough to perform a routine pathological analysis.
5. 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.
6. 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.
7. 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.
8. 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).
9. 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.

Primary outcomes:
measure: Progression-free survival
timeFrame: 1 year
Secondary outcomes:
measure: Overall survival
timeFrame: 72 weeks
measure: Disease control rate
timeFrame: an average of 1 year
measure: Changes in tumor volume shrinking
timeFrame: 6 months
measure: Prediction of the response to treatment by the patient-derived organoids
timeFrame: 2 years
measure: The rate of successful generation of lung cancer organoids
timeFrame: 2 years
Other outcomes:
Locations:
city: Wuxi
country: China
facility: Affiliated Hospital of Jiangnan University
state: Jiangsu
Study officials:
affiliation: Affiliated Hospital of Jiangnan University
name: quan liu, doctor
role: PRINCIPAL_INVESTIGATOR
References: