Neuroendocrine Carcinoma of LungLINEARNCT07429851
CompArative Analysis Between, Thymic, pulmonaRy and Pancreatic Well Differentiated High Grade Neuroendocrine Tumors
An observational study of Neuroendocrine Carcinoma of Lung and Neuroendocrine Carcinoma of Thymus, run by European Institute of Oncology at 1 site in Italy.
Trial summary
The study involves the enrollment of 34 patients diagnosed with advanced thymic, pulmonary and duodeno-pancreatic well-differentiated high grade neuroendocrine tumors (Ki-67 > 20%). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Neuroendocrine Carcinoma of Lung, Neuroendocrine Carcinoma of Thymus
- How many people
- 34 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jan 2026to 31 Mar 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Histologically confirmed diagnosis of thymic, pulmonaRy and pancreatic well differentiated high grade neuroendocrine tumors(Ki-67 > 20% according to WHO 2022)
Who may be able to join
- Histologically confirmed diagnosis of well-differentiated high grade neuroendocrine tumor (Ki-67 > 20% according to WHO 2022) performed or reviewed by a NEN-dedicated pathologist.
- Primary tumor site:thyme, lung and duodenum-pancreas NETs.
- Advanced stage of tumor disease and Any number of lines of therapy
- Sufficient available clinical data on diagnosis, treatments, outcomes.
Who cannot join
- Poorly differentiated neuroendocrine carcinomas (NECs), GEP NET G1/G2, pulmonary carcinoid with Ki-67 < 20%.
- Diagnosis of mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs)
- Inadequate or unavailable tumor tissue for molecular analysis.
- Incomplete clinical records or follow-up.
- Other primary sites, except lung or pancreas.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
European Institute of Oncology
Milan, Italy, 20141
Cristiana Mulargiu, MD, 00390257489258, divisione.gastrointestinale@ieo.it
Francesca Spada, MD, 00390257489258, divisione.gastrointestinale@ieo.it
About this study
Official title: CLINical, Pathological and outcomE compArative Analysis Between, Thymic, pulmonaRy and Pancreatic Well Differentiated High Grade Neuroendocrine Tumors: a Retrospective Observational Study
The study involves the enrollment of 34 patients diagnosed with advanced thymic, pulmonary and duodeno-pancreatic well-differentiated high grade neuroendocrine tumors (Ki-67 > 20%). The objective of this retrospective single-centre translational study will be to explore whether patients differ clinically in terms of diagnosis and treatment management. Currently, well differentiated high grade pulmonary NETs are managed using extrapolated algorithms from duodeno-pancreatic NETs, underlining a significant unmet clinical need. This is likely due to the rarity, uncertain pathological and molecular classification, and heterogeneous clinical course of well differentiated high grade pulmonary NETs.
In this study a retrospective data-base of pulmonary, thymic and duodeno-pancreatic NETs with Ki-67 > 20% will be created in order to analyze diagnostic and therapeutic pathways, clinical outcomes, imaging, disease evolution and molecular profiling. This study will adopt a hypothesis-generating approach to explore whether patients in these distinct groups differ clinically in terms of diagnosis and treatment management.
Read the detailed description
The LINEAR study aims to address unmet medical clinical needs in LNETs. This project specifically focuses on lung and thymic advanced NETs with Ki-67 > 20%, a rare subtype of lung cancer subtypes characterized by heterogeneous biological behaviour and variable clinical course. This contrasts with duodeno-pancreatic NETs, for which a higher level of evidence currently guides treatment sequencing. The molecular landscape and optimal therapeutic strategies for thymic and LNETs remain under investigation and are currently based on pathological features and metabolic imaging findings. Some LNETS present a carcinoids morphology but exhibit elevated Ki67 indices (often exceeding 20-30%), and these and appear to share similar behaviour and clinical characteristics with well differentiated high grade duodeno-pancreatic NETs (ki-67>20%). Such clinical cases fall into a "grey zone" where treatment prioritization is challenging due to limited data and lack of clear guidelines.
The primary endpoint of this study will be to compare therapeutic algorithm applied to well-differentiated duodeno-pancreatic, thymic and lung NETs with high proliferative indices (Ki-67 > 20%) based on the hypothesis that patients belonging to these distinct groups do not differ significantly from a clinical point of view in terms of diagnosis and treatment management.
Secondarily we will investigate the correlation of genomic alterations with patients' outcome and treatment activity and efficacy.
- To compare overall survival (OS) in the two groups.
- To compare first line progression-free survival (PFS) and time to progression (TTP) in the histological groups.
- To assess treatment response across lines of therapy, including response rate (RR), disease control rate (DCR), and treatment duration in both cohorts.
- To correlate specific genetic alterations with clinical outcomes (OS, PFS).
- To explore potential actionable molecular targets and their distribution across the two tumor origins.
- Keywords
- therapeutic algorithm, overall survival, first line progression-free survival, time to progression, genetic alterations, clinical outcomes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| thymic and pulmonary neuroendocrine neoplasms | thymic and pulmonary well differentiated high grade Advanced stage neuroendocrine tumor | |
| gastroenteropancreatic neuroendocrine neoplasms | gastroenteropancreatic well differentiated high grade neuroendocrine Advanced stage neuroendocrine tumor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Therapeutic algorithm
The primary endpoint of this study will be to compare therapeutic algorithm applied to the two grups: well-differentiated duodeno-pancreatic, versus thymic and lung NETs with high proliferative indices.
Measured: 3 months
Secondary outcomes (4)
overall survival
To compare overall survival (OS) in the two groups.
Measured: 3 months
First line progression-free survival
To compare first line progression-free survival (PFS) in the histological groups.
Measured: 3 months
treatment response across lines of therapy
To assess treatment response across lines of therapy, in both cohorts.
Measured: 3 months
genetic alterations
To correlate specific genetic alterations with clinical outcomes (OS, PFS). To explore potential actionable molecular targets and their distribution across the two tumor origins.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2026
- Study start1 Jan 2026
- Primary completion31 Mar 2026 (estimated)
- Study completion31 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuroendocrine Carcinoma of LungStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- European Institute of Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicola Fazio, MD, Principal investigator, IEO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07429851
- Sponsor's protocol ID
- UID 5263
- Other IDs
- L2-518
- Acronym
- LINEAR
- Status last verified
- Jan 2026
- First submitted
- 5 Feb 2026
- Last updated
- 24 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CLINical, Pathological and outcomE compArative Analysis Between, Thymic, pulmonaRy and Pancreatic Well Differentiated High Grade Neuroendocrine Tumors: a Retrospective Observational Study
- ClinicalTrials.gov ID
- NCT07429851
- Acronym / sponsor ID
- LINEAR / UID 5263
- Keywords
- therapeutic algorithm, overall survival, first line progression-free survival, time to progression, genetic alterations, clinical outcomes
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- European Institute of OncologyUniversity, hospital or other
- Study start
- 1 Jan 2026 (actual)
- Primary completion
- 31 Mar 2026 (estimated)
- Study completion
- 31 Mar 2026 (estimated)
- First posted
- 24 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study involves the enrollment of 34 patients diagnosed with advanced thymic, pulmonary and duodeno-pancreatic well-differentiated high grade neuroendocrine tumors (Ki-67 > 20%). The objective of this retrospective single-centre translational study will be to explore whether patients differ clinically in terms of diagnosis and treatment management. Currently, well differentiated high grade pulmonary NETs are managed using extrapolated algorithms from duodeno-pancreatic NETs, underlining a significant unmet clinical need. This is likely due to the rarity, uncertain pathological and molecular classification, and heterogeneous clinical course of well differentiated high grade pulmonary NETs.
In this study a retrospective data-base of pulmonary, thymic and duodeno-pancreatic NETs with Ki-67 > 20% will be created in order to analyze diagnostic and therapeutic pathways, clinical outcomes, imaging, disease evolution and molecular profiling. This study will adopt a hypothesis-generating approach to explore whether patients in these distinct groups differ clinically in terms of diagnosis and treatment management.
Detailed description
The LINEAR study aims to address unmet medical clinical needs in LNETs. This project specifically focuses on lung and thymic advanced NETs with Ki-67 > 20%, a rare subtype of lung cancer subtypes characterized by heterogeneous biological behaviour and variable clinical course. This contrasts with duodeno-pancreatic NETs, for which a higher level of evidence currently guides treatment sequencing. The molecular landscape and optimal therapeutic strategies for thymic and LNETs remain under investigation and are currently based on pathological features and metabolic imaging findings. Some LNETS present a carcinoids morphology but exhibit elevated Ki67 indices (often exceeding 20-30%), and these and appear to share similar behaviour and clinical characteristics with well differentiated high grade duodeno-pancreatic NETs (ki-67>20%). Such clinical cases fall into a "grey zone" where treatment prioritization is challenging due to limited data and lack of clear guidelines.
The primary endpoint of this study will be to compare therapeutic algorithm applied to well-differentiated duodeno-pancreatic, thymic and lung NETs with high proliferative indices (Ki-67 > 20%) based on the hypothesis that patients belonging to these distinct groups do not differ significantly from a clinical point of view in terms of diagnosis and treatment management.
Secondarily we will investigate the correlation of genomic alterations with patients' outcome and treatment activity and efficacy.
- To compare overall survival (OS) in the two groups.
- To compare first line progression-free survival (PFS) and time to progression (TTP) in the histological groups.
- To assess treatment response across lines of therapy, including response rate (RR), disease control rate (DCR), and treatment duration in both cohorts.
- To correlate specific genetic alterations with clinical outcomes (OS, PFS).
- To explore potential actionable molecular targets and their distribution across the two tumor origins.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| thymic and pulmonary neuroendocrine neoplasms | – | –thymic and pulmonary well differentiated high grade Advanced stage neuroendocrine tumor |
| gastroenteropancreatic neuroendocrine neoplasms | – | –gastroenteropancreatic well differentiated high grade neuroendocrine Advanced stage neuroendocrine tumor |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Histologically confirmed diagnosis of thymic, pulmonaRy and pancreatic well differentiated high grade neuroendocrine tumors(Ki-67 > 20% according to WHO 2022)
Key inclusion criteria (4 listed)
- Histologically confirmed diagnosis of well-differentiated high grade neuroendocrine tumor (Ki-67 > 20% according to WHO 2022) performed or reviewed by a NEN-dedicated pathologist.
- Primary tumor site:thyme, lung and duodenum-pancreas NETs.
- Advanced stage of tumor disease and Any number of lines of therapy
- Sufficient available clinical data on diagnosis, treatments, outcomes.
Key exclusion criteria (5 listed)
- Poorly differentiated neuroendocrine carcinomas (NECs), GEP NET G1/G2, pulmonary carcinoid with Ki-67 < 20%.
- Diagnosis of mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs)
- Inadequate or unavailable tumor tissue for molecular analysis.
- Incomplete clinical records or follow-up.
- Other primary sites, except lung or pancreas.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Therapeutic algorithm
Time frame: 3 months
The primary endpoint of this study will be to compare therapeutic algorithm applied to the two grups: well-differentiated duodeno-pancreatic, versus thymic and lung NETs with high proliferative indices.
4 secondary outcomes
overall survival
Time frame: 3 months
First line progression-free survival
Time frame: 3 months
treatment response across lines of therapy
Time frame: 3 months
genetic alterations
Time frame: 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nicola Fazio, MD principal investigator
IEO
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neuroendocrine Carcinoma of Lung and Neuroendocrine Carcinoma of Thymus, run by European Institute of Oncology at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Cristiana Mulargiu, MD (00390257489258, divisione.gastrointestinale@ieo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Therapeutic algorithm (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2026.