Well-Differentiated Neuroendocrine Tumors (NETs)SEQUENCE-NETNCT07890012
Real World Positioning of Tyrosine Kinase Inhibitors (TKIs) Within Systemic Treatment Strategies for Advanced Neuroendocrine Tumors (NETs)
An observational study of Well-Differentiated Neuroendocrine Tumors (NETs), run by Hospices Civils de Lyon at 18 sites in France.
Trial summary
Well differentiated neuroendocrine tumors (NETs) are rare and heterogeneous malignancies that frequently evolve toward advanced or metastatic disease, requiring long-term systemic treatment strategies delivered over multiple lines. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Well-Differentiated Neuroendocrine Tumors (NETs)
- What is being tested?
- PRO-CSS questionnaire
- How many people
- 100 participants
- Where
- 18 sitesFrance
- Study dates
- 1 Jan 2027to 1 Jul 2028
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Eligible patients are adults with histologically confirmed, well-differentiated, advanced (metastatic or unresectable) NETs (G1-G3) initiating a TKI in routine clinical practice. The patients will be recruited from the expert centers of ENDOCAN's RENATEN network or affiliated collaborating centers participating in SEQUENCE's study.
Who may be able to join
- For main study :
- Adult patients (≥ 18 years of age).
- Histologically confirmed advanced (metastatic or unresectable) well-differentiated NET of grade G1, G2, or G3 according to the WHO classification.
- Initiation of a TKI in routine clinical practice, serving as the index treatment line for prospective inclusion.
- Patient informed about the study with documented non-opposition, in accordance with applicable regulations.
- For the ancillary study :
- Advanced/metastatic NETs (usually, ileal or lung NET, but other rare location/unknown are allowed) with clinical carcinoid syndrome and/or elevation of urinary 5HIAA> 2 upper limit of normal (ULN) Initiation of TKI in routine clinical practice, serving as the index treatment line for prospective inclusion.
Who cannot join
- For main study :
- Poorly differentiated neuroendocrine carcinomas (NEC), including MiNEN with a NEC component.
- Participation in an ongoing phase I, II, or III interventional clinical trial evaluating an investigational systemic therapy at the time of inclusion.
- Missing minimal required data preventing reconstruction of prior systemic treatment sequences or assessment of prospective endpoints.
- For the ancillary study :
- Patient not wanting to participate (filling in the questionnaires)
Trial locations and contacts
18 sites in 1 country. Contact the study team or a site near you to ask about taking part.
18 sites in 1 country
France18 sites
CHU Angers
Angers, 49933
Dr Sandrine LABOUREAU, +33 2 41 35 45 93, salaboureau@chu-angers.fr
Sandrine LABOUREAU, MD, PhD
CHU de Caen
Caen, 14000
Dr Karine BOUHIER-LEPORRIER, +33 2 31 06 45 37, bouhierleporrier-k@chu-caen.fr
Karine BOUHIER-LEPORRIER, MD, PhD
Hôpital Beaujon APHP
Clichy, 92110
Dr Louis de MESTIER, +33 1 40 87 57 28, louis.demestier@aphp.fr
Louis de MESTIER, Professor
CHU Dijon Bourgogne
Dijon, 21079
Pr Côme LEPAGE, +33 3 80 29 37 50, come.lepage@u-bourgogne.fr
Côme LEPAGE, Professor
CHU Grenoble-Alpes
La Tronche, 38700
Dr Victoire GRANGER, +33 4 76 76 58 01, VGranger@chu-grenoble.fr
Victoire GRANGER, MD, PhD
CHRU de Lille - Hôpital Claude Huriez
Lille, 59037
Dr Arnaud JANNIN, +33 3 20 44 45 18, arnaud.jannin@chu-lille.fr
Arnaud JANNIN, MD, PhD
Hôpital Edouard Herriot
Lyon, 69437
Pr Thomas WALTER, +33 4.72.11.00.94, thomas.walter@chu-lyon.fr
Thomas WALTER, Professor
CHU Nantes
Nantes, 44093
Dr Alexandre LUGAT, +33 2 40 16 59 30, alexandre.lugat@chu-nantes.fr
Alexandre LUGAT, MD, PhD
Institut Curie
Paris, 75005
Dr Ségolène HESCOT, + 33147111584, segolene.hescot@curie.fr
Ségolène HESCOT, MD, PhD
Hôpital Saint Antoine APHP
Paris, 75012
Dr Pauline AFCHAIN, +33 1 49 28 23 27, pauline.afchain@aphp.fr
Pauline AFCHAIN, MD, PhD
Hôpital Cochin APHP
Paris, 75014
Pr Romain CORIAT, +33 1 58 41 19 52, romain.coriat@aphp.fr
Romain CORIAT, Professor
Hôpital Européen Georges Pompidou
Paris, 75015
Dr Céline LEPERE, +33 1 56 09 35 55, celine.lepere@aphp.fr
Céline LEPERE, MD, PhD
CHU Bordeaux- Hôpital Haut-Lévêque
Pessac, 33600
Dr Denis SMITH, +33 5 57 65 64 39, denis.smith@chu-bordeaux.fr
Denis SMITH, MD, PhD
CHU Poitiers
Poitiers, 86021
Dr Aurélie FERRU, +33 5 49 44 43 21, a.ferru@chu-poitiers.fr
FERRU Aurélie, MD, PhD
CHU Reims - Hôpital Robert Debré
Reims, 51092
Dr Marine PERRIER, + 33 3 26 78 84 41, mperrier@chu-reims.fr
Marine PERRIER, MD, PhD
CHRU Strasbourg - Hôpital de Hautepierre
Strasbourg, 67098
Dr Philippe BALTZINGER, +33 3 88 12 76 00, philippe.baltzinger@chru-strasbourg.fr
Philippe BALTZINGER, MD, PhD
CHU Tours - Hôpital Trousseau
Tours, 37044
Pr Thierry LECOMTE, +33 2 47 47 91 71, thierry.lecomte@univ-tours.fr
Thierry LECOMTE, Professor
Institut Gustave Roussy
Villejuif, 94805
Dr Julien HADOUX, +33 142116361, Julien.hadoux@gustaveroussy.fr
Julien HADOUX, MD, PhD
About this study
Well differentiated neuroendocrine tumors (NETs) are rare and heterogeneous malignancies that frequently evolve toward advanced or metastatic disease, requiring long-term systemic treatment strategies delivered over multiple lines. Their management is complex and influenced by tumor-related factors-including primary site and grade-as well as disease burden, functional status, patient comorbidities, and access to available therapeutic options. As a result, real-world treatment pathways in advanced NETs are highly diverse.
In recent years, the systemic treatment landscape of advanced NETs has expanded beyond somatostatin analogues (SSA), peptide receptor radionuclide therapy (PRRT), and chemotherapy to include targeted therapies. Among these, multitarget tyrosine kinase inhibitors (TKIs) targeting tumor angiogenesis have progressively been incorporated into clinical practice. Their use varies according to tumor subtype, disease dynamics, prior treatments, and patient-related considerations, reflecting the absence of standardized sequencing algorithms.
Read more
In routine clinical practice, the choice and sequencing of TKIs are driven by individualized clinical decision-making rather than predefined treatment pathways. Their positioning within systemic treatment strategies is influenced by anticipated benefit, tolerability, prior toxicities, and practical constraints such as regulatory indications, access, and reimbursement conditions, which differ by tumor origin. Consequently, the real-world positioning of TKIs within treatment sequences remains insufficiently characterized at a national level.
"SEQUENCE-NET" is an ambispective observational study designed to prospectively document how TKIs are integrated into systemic treatment strategies for advanced pancreatic and extra-pancreatic NETs in routine clinical practice within the ENDOCAN-RENATEN network.
- Being tested
- PRO-CSS questionnaire
- Keywords
- TKI treatment, ENDOCAN RENATEN network
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PRO-CSS questionnaireOther
PRO-CSS is a validated patient-reported questionnaire designed to assess the severity of carcinoid syndrome symptoms and their impact on daily life. It evaluates symptoms such as diarrhoea, flushing, urgency, abdominal pain, and fatigue, as well as their effects on daily activities, diet, travel, and overall quality of life. The questionnaire provides a standardized assessment of symptom burden from the patient's perspective and may help monitor symptom control over time. The questionnaire must be completed at baseline, than at 1, 2 and 3 months after TKI's treatment started.
| Study group | Role | What they receive |
|---|---|---|
| Main group | Adults patients with histologically confirmed, well differentiated, advanced (metastatic or unresectable) NETs (G1-G3) initiating a TKI in routine clinical practice. These patients will have no intervention | |
| Ancillary group | Adult patients with histologically confirmed, well-differentiated, advanced (metastatic or unresectable) neuroendocrine tumors (NETs; G1-G3) and clinical carcinoid syndrome who initiated tyrosine kinase inhibitor (TKI) therapy in routine clinical practice. Patients will respond to the PRO-CSS (Patient-Reported Outcome measure for Carcinoid Syndrome Symptoms) questionnaire Receives: Other: PRO-CSS questionnaire |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment distribution and therapeutic sequencing
Proportion of patients receiving TKIs at inclusion according to treatment lines and the distribution of prior systemic treatment sequences before TKI initiation
Measured: From treatment initiation through 9 months of follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2026
- Study start1 Jan 2027 (estimated)
- Primary completion1 Jul 2028 (estimated)
- Study completion1 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Well-Differentiated Neuroendocrine Tumors (NETs)Studies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- 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
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Collaborators
- IPSEN PHARMA S.A.S, ENDOCAN RENATEN network
- Responsible party
- Sponsor
- Investigators
- Thomas WALTER, Professor, Principal investigator, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07890012
- Sponsor's protocol ID
- 69HCL26_0625
- Acronym
- SEQUENCE-NET
- Status last verified
- Oct 2026
- First submitted
- 16 Oct 2026
- Last updated
- 22 Oct 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 22 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Real World Positioning of Tyrosine Kinase Inhibitors (TKIs) Within Systemic Treatment Strategies for Advanced Neuroendocrine Tumors (NETs)
- ClinicalTrials.gov ID
- NCT07890012
- Acronym / sponsor ID
- SEQUENCE-NET / 69HCL26_0625
- Keywords
- TKI treatment, ENDOCAN RENATEN network
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Collaborators
- IPSEN PHARMA S.A.S, ENDOCAN RENATEN network
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- 1 Jul 2028 (estimated)
- Study completion
- 1 Jul 2028 (estimated)
- First posted
- 22 Oct 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.
Well differentiated neuroendocrine tumors (NETs) are rare and heterogeneous malignancies that frequently evolve toward advanced or metastatic disease, requiring long-term systemic treatment strategies delivered over multiple lines. Their management is complex and influenced by tumor-related factors-including primary site and grade-as well as disease burden, functional status, patient comorbidities, and access to available therapeutic options. As a result, real-world treatment pathways in advanced NETs are highly diverse.
In recent years, the systemic treatment landscape of advanced NETs has expanded beyond somatostatin analogues (SSA), peptide receptor radionuclide therapy (PRRT), and chemotherapy to include targeted therapies. Among these, multitarget tyrosine kinase inhibitors (TKIs) targeting tumor angiogenesis have progressively been incorporated into clinical practice. Their use varies according to tumor subtype, disease dynamics, prior treatments, and patient-related considerations, reflecting the absence of standardized sequencing algorithms.
In routine clinical practice, the choice and sequencing of TKIs are driven by individualized clinical decision-making rather than predefined treatment pathways. Their positioning within systemic treatment strategies is influenced by anticipated benefit, tolerability, prior toxicities, and practical constraints such as regulatory indications, access, and reimbursement conditions, which differ by tumor origin. Consequently, the real-world positioning of TKIs within treatment sequences remains insufficiently characterized at a national level.
"SEQUENCE-NET" is an ambispective observational study designed to prospectively document how TKIs are integrated into systemic treatment strategies for advanced pancreatic and extra-pancreatic NETs in routine clinical practice within the ENDOCAN-RENATEN network.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Main group | – | –Adults patients with histologically confirmed, well differentiated, advanced (metastatic or unresectable) NETs (G1-G3) initiating a TKI in routine clinical practice. These patients will have no intervention |
| Ancillary group | – | Other: PRO-CSS questionnaireAdult patients with histologically confirmed, well-differentiated, advanced (metastatic or unresectable) neuroendocrine tumors (NETs; G1-G3) and clinical carcinoid syndrome who initiated tyrosine kinase inhibitor (TKI) therapy in routine clinical practice. Patients will respond to the PRO-CSS (Patient-Reported Outcome measure for Carcinoid Syndrome Symptoms) questionnaire |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Eligible patients are adults with histologically confirmed, well-differentiated, advanced (metastatic or unresectable) NETs (G1-G3) initiating a TKI in routine clinical practice. The patients will be recruited from the expert centers of ENDOCAN's RENATEN network or affiliated collaborating centers participating in SEQUENCE's study.
Key inclusion criteria (7 listed)
- Adult patients (≥ 18 years of age).
- Histologically confirmed advanced (metastatic or unresectable) well-differentiated NET of grade G1, G2, or G3 according to the WHO classification.
- Initiation of a TKI in routine clinical practice, serving as the index treatment line for prospective inclusion.
- Patient informed about the study with documented non-opposition, in accordance with applicable regulations.
- Advanced/metastatic NETs (usually, ileal or lung NET, but other rare location/unknown are allowed) with clinical carcinoid syndrome and/or elevation of urinary 5HIAA> 2 upper limit of normal (ULN) Initiation of TKI in routine clinical practice, serving as the index treatment line for prospective inclusion.
Key exclusion criteria (6 listed)
- Poorly differentiated neuroendocrine carcinomas (NEC), including MiNEN with a NEC component.
- Participation in an ongoing phase I, II, or III interventional clinical trial evaluating an investigational systemic therapy at the time of inclusion.
- Missing minimal required data preventing reconstruction of prior systemic treatment sequences or assessment of prospective endpoints.
- Patient not wanting to participate (filling in the questionnaires)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PRO-CSS questionnairePRO-CSS is a validated patient-reported questionnaire designed to assess the severity of carcinoid syndrome symptoms and their impact on daily life. It evaluates symptoms such as diarrhoea, flushing, urgency, abdominal pain, and fatigue, as well as their effects on daily activities, diet, travel, and overall quality of life. The questionnaire provides a standardized assessment of symptom burden from the patient's perspective and may help monitor symptom control over time. The questionnaire must be completed at baseline, than at 1, 2 and 3 months after TKI's treatment started. | Other | Ancillary group |
Primary outcome
Treatment distribution and therapeutic sequencing
Time frame: From treatment initiation through 9 months of follow-up
Proportion of patients receiving TKIs at inclusion according to treatment lines and the distribution of prior systemic treatment sequences before TKI initiation
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 22 Oct 2026.
Related trials for Well-Differentiated Neuroendocrine Tumors (NETs)
RecruitingPhase 1
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GEP-NET, Gastroenteropancreatic Neuroendocrine Tumor
Not yet recruitingPhase 3
TRINITY TRIAL; Trial Of PRRT Plus CAPTEM Vs CAPTEM Alone In Well Differentiated GEP NETS
Gastroenteropancreatic Neuroendocrine Tumors
Active, not recruitingPhase 3
Study of RYZ101 Compared With SOC in Pts w Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy
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Active, not recruitingPhase 1
Testing the Addition of an Anti-cancer Drug, Triapine, to the Usual Radiation-Based Treatment (Lutetium Lu 177 Dotatate) for Neuroendocrine Tumors
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RecruitingPhase 3
Study to Evaluate the Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Patients With Grade 1 and Grade 2 Advanced GEP-NET
Somatostatin Receptor Positive (SSTR+), Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET)
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.
Thomas WALTER, Professor principal investigator
Hospices Civils de Lyon
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Well-Differentiated Neuroendocrine Tumors (NETs), run by Hospices Civils de Lyon at 18 sites in France.
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 7 inclusion and 6 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: opening soon, as of the sponsor's last update on 22 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in France. 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 Pr Thomas WALTER (+33 4.72.11.00.94, thomas.walter@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment distribution and therapeutic sequencing (time frame: From treatment initiation through 9 months of follow-up). 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 22 Oct 2026.