Understanding how non-small cell lung cancer transforms into neuroendocrine carcinoma

Neuroendocrine Transformation in RB1 and TP53 Inactivated Non-small Cell Lung Cancer Patients: a Multi-center Prospective Observational Study

Observational Fudan University · NCT06369181

This study is trying to see how non-small cell lung cancer changes into a different type called neuroendocrine carcinoma in patients with certain gene mutations who have stopped responding to their current treatments.

Quick facts

Study typeObservational
Enrollment50 (estimated)
Ages18 Years and up
SexAll
SponsorFudan University Academic / other
Drugs / interventionschemotherapy, immunotherapy, radiation
Locations1 site (Shanghai, Shanghai Municipality)
Trial IDNCT06369181 on ClinicalTrials.gov

What this trial studies

This observational study investigates the transformation of non-small cell lung cancer (NSCLC) into neuroendocrine carcinoma (NEC), particularly focusing on cases where patients have mutations in the RB1 and TP53 genes. The study aims to identify the occurrence of this transformation in NSCLC patients who have developed resistance to tyrosine kinase inhibitors (TKIs) and to explore the correlation between gene inactivation and the risk of NEC transformation. By analyzing patient data and conducting follow-up biopsies, the researchers hope to better understand this rare mechanism and its implications for treatment. The study emphasizes the importance of re-biopsy in recognizing histological changes in lung cancer patients.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with stage III-IV non-small cell lung cancer who have confirmed dual inactivation of RB1 and TP53.

Not a fit: Patients who do not have stage III-IV non-small cell lung cancer or those without RB1/TP53 gene inactivation may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and management of treatment-resistant lung cancer, potentially guiding more effective therapeutic strategies.

How similar studies have performed: Previous studies have indicated the occurrence of neuroendocrine transformation in NSCLC, suggesting that this area of research is gaining recognition but still requires further exploration.

Eligibility criteria

Show full 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.

Where this trial is running

Shanghai, Shanghai Municipality

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Neuroendocrine CarcinomaNon-small Cell Lung CancerHistology Transformationneuroendocrine transformationsmall cell lung cancer transformationTP53RB1histology transformation
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.