Neuroendocrine Transformation in RB1/TP53 Inactivated NSCLC

Study Purpose

Histology transformation from non-small cell lung cancer (NSCLC) to neuroendocrine carcinomas (NEC), especially from epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma (LADC) to small cell lung cancer (SCLC), is widely recognized as a rare mechanism for NSCLC to confer tyrosine kinase inhibitors (TKIs) resistance. The probability of its occurrence is about 3-14% in NSCLC patients who are resistant to TKI treatment. In addition to EGFR mutations, NSCLC patients carrying ALK/ROS1 mutations and receiving corresponding TKI treatment may also experience NEC transformation(NET). In a previous study [Pubmed ID: 35609408], the investigators demonstrated that NET also develops in NSCLCs without TKI targets or treatments. This phenomenon could be under-recognized, because re-biopsy was less frequently performed in these patients. The investigators had also shown that p53/Rb inactivation might correlated with NET and should be considered for NET risk prediction. In another retrospective studies, it was found that NSCLC patients with RB1/TP53 dual inactivation mutations had a significantly higher probability of NEC pathological transformation than those without RB1/TP53 inactivation mutations (43 times higher than those without mutations). Therefore, the subgroup of NSCLC patients with tumor suppressor gene RB1/TP53 dual inactivation might have elevated risk for NET. In this study, the investigators proposed to prospectively follow up NSCLC patients with dual RB1/TP53 inactivation (approximately 5% of the total NSCLC). Through prospective and systematic collection of baseline pathological information, clinical treatment process, and imaging data, and as much as possible, repeat pathological biopsies will be performed during disease progression.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Observational
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Age ≥ 18 years old; 2. ECOG function status score 0-2 points; 3. Pathological diagnosis of stage III-IV non neuroendocrine non-small cell lung cancer; 4. RB1/TP53 gene/protein testing (IHC, NGS, or other techniques are acceptable) has been completed and confirmed to be dual inactivation of RB1/TP53; 5. For patients with baseline pathology of adenocarcinoma, complete driver gene testing (including at least EGFR and ALK); 6. The patient undergoes at least one systemic treatment (chemotherapy, targeted drug therapy, immunotherapy, etc.) and receives regular follow-up; 7. After discovering disease progression during the follow-up process, the patient will undergo further pathological biopsy of the progressing lesion after evaluation by the sub center PI; 8. According to the researcher's assessment, the patient currently does not require palliative radiation therapy in any area; 9. If the subject undergoes surgery, they must fully recover from the toxicity and complications of the surgical intervention before starting treatment; 10. The subjects need to agree to provide corresponding peripheral blood and biopsy tissue samples before and during the follow-up treatment in accordance with the clinical trial protocol requirements; 11. Men/women of childbearing age agree to use contraception during the trial period (surgical ligation or oral contraception/intrauterine device+condom contraception); 12. Life expectancy ≥ 3 months; 13. Patients must have the ability to understand and voluntarily sign informed consent forms.

Exclusion Criteria:

1. Baseline pathological examination reveals neuroendocrine components (including any percentage of small cell carcinoma, large cell carcinoma, differentiated neuroendocrine carcinoma, etc); 2. Unable to perform RB1/TP53 testing ; 3. Patients with baseline pathology of adenocarcinoma and inability to perform driver gene testing (including at least EGFR, ALK); 4. Symptomatic interstitial lung disease or active infection/non infectious pneumonia; 5. History of other malignant tumors; 6. Physical examination or clinical trial findings that researchers believe may interfere with the results or increase the risk of treatment complications for patients, or other uncontrollable diseases. 7. Breastfeeding or pregnant women; 8. Congenital or acquired immunodeficiency diseases, including human immunodeficiency virus (HIV), or a history of organ transplantation or allogeneic stem cell transplantation; 9. Patients who require long-term treatment with cortisol or immunosuppressants; 10. Patients with mental illnesses, substance abuse, or social issues that affect compliance will not be included in the group after being reviewed by a doctor. 11. Individuals who receive other long-term medication treatments and have been assessed by a doctor as potentially affecting disease progression.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT06369181
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Fudan University
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries China
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Neuroendocrine Carcinoma, Non-small Cell Lung Cancer, Histology Transformation

Contact a Trial Team

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International Sites

Fudan University Shanghai Cancer Center, Shanghai, Shanghai, China

Status

Recruiting

Address

Fudan University Shanghai Cancer Center

Shanghai, Shanghai, 200032

Site Contact

Zhengfei Zhu, MD

[email protected]

+86 18017312901

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