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Liver Transplantation Versus Conventional Medical Therapy for Low-Grade GEP-NET With Liver Metastases (TRANET-GEP)

28 oktober 2026 bijgewerkt door: Chiyi Chen

Liver Transplantation Compared With Conventional Medical Therapy for Well-Differentiated (G1/G2) Gastroenteropancreatic Neuroendocrine Tumors With Unresectable Liver Metastases: A Two-Center, Non-Randomized, Patient-Preference-Based Prospective Cohort Study

Liver Transplantation Versus Conventional Medical Therapy for Low-Grade GEP-NET With Liver Metastases

Studie Overzicht

Toestand

Aanmelden op uitnodiging

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of neoplasms; when liver metastases occur, prognosis deteriorates substantially. For patients with low-grade (well-differentiated G1/G2, low Ki-67 proliferation index), liver-dominant, unresectable metastases, conventional medical therapy-including somatostatin analogues, molecular targeted agents, peptide receptor radionuclide therapy (PRRT), and locoregional transarterial treatments-offers disease control but limited survival benefit, with an estimated 5-year overall survival below 30%.

Liver transplantation has emerged as a potentially curative option for highly selected patients with unresectable NET liver metastases. Non-randomized data from specialized centers suggest that patients meeting strict selection criteria (well-differentiated histology, low proliferative index, no uncontrolled extrahepatic disease) may achieve a 5-year overall survival of approximately 70% after transplantation. However, the absence of a concurrently enrolled non-transplant comparator group has limited the evidence.

This study establishes a two-center, prospective, non-randomized cohort in which treatment selection (liver transplantation versus conventional medical therapy) is based on patient/family preference following multidisciplinary evaluation at each center, with both groups intended to be broadly comparable at baseline. Liver transplantation is performed at the Department of Liver Transplantation, Tianjin First Central Hospital; conventional medical therapy is delivered at Fudan University Shanghai Cancer Center.

The primary objective is to compare 5-year overall survival between the two groups. Secondary objectives include 1- and 3-year overall survival, progression-free survival, post-transplant disease-free survival and recurrence patterns, safety and treatment-related morbidity, quality of life, and health economic outcomes.

Because assignment is not randomized, baseline comparability will be assessed and adjusted using propensity score matching or inverse probability of treatment weighting, complemented by multivariable Cox proportional hazards regression. Exploratory subgroup analyses will be performed by tumor grade, Ki-67 index, primary tumor site, and hepatic tumor burden.

Studietype

Observationeel

Inschrijving (Geschat)

100

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • China
    • Tianjin Municipality
      • Tianjin, Tianjin Municipality, China, 300192
        • Tianjin Firsr Central Hospital

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 70 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Ja

Geslachten die in aanmerking komen voor studie

Allemaal

Bemonsteringsmethode

Kanssteekproef

Studie Bevolking

Adult patients (aged 18-70 years) with histologically confirmed, well-differentiated (G1/G2) gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and unresectable, liver-dominant metastases, with Ki-67 proliferation index ≤ 10% and ECOG performance status 0-1. The population includes two cohorts: (1) patients who undergo liver transplantation at Tianjin First Central Hospital and (2) patients with comparable baseline characteristics who receive conventional medical therapy at Fudan University Shanghai Cancer Center, with cohort assignment based on patient/family preference following balanced multidisciplinary counseling. Both cohorts are drawn from consecutive patients meeting the eligibility criteria at the two participating centers between January 2019 and December 2028.

Beschrijving

Inclusion Criteria:

  1. Age 18-70 years at enrollment.
  2. Histologically confirmed, well-differentiated (G1 or G2) gastroenteropancreatic neuroendocrine tumor (pancreatic or midgut/hindgut primary).
  3. Unresectable, liver-dominant metastatic disease (multifocal/bilobar involvement not amenable to curative resection or ablation).
  4. Ki-67 proliferation index ≤ 10% at the most recent biopsy, with stable disease for at least 6 months on standard therapy.
  5. Primary tumor resected, or resectable/planned for resection as part of the treatment strategy.
  6. No uncontrolled extrahepatic metastatic disease.
  7. ECOG performance status 0-1.
  8. Treatment group assigned by patient/family preference after balanced multidisciplinary counseling; both options (transplantation vs conventional therapy) medically feasible and discussed.
  9. Written informed consent.

Exclusion Criteria:

  1. Poorly differentiated neuroendocrine carcinoma (G3, Ki-67 above threshold) or mixed neuroendocrine/non-neuroendocrine neoplasm (MiNEN).
  2. Uncontrolled extrahepatic metastases or progressive disease despite adequate systemic therapy at enrollment.
  3. For candidates considering transplantation: serious comorbidities precluding major surgery, including uncontrolled cardiopulmonary disease, active infection, decompensated cirrhosis with severe portal hypertension, or other contraindications to transplantation and immunosuppression.
  4. Pregnancy or lactation.
  5. Other active malignancy within the past 5 years (except adequately treated non-melanoma skin cancer or cervical carcinoma in situ).
  6. Inability or unwillingness to comply with protocol follow-up.
  7. Participation in another interventional clinical trial with potential interference with endpoints.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Observatiemodellen: COHORT
  • Tijdsperspectieven: PROSPECTIVE

Cohorten en interventies

Groep / Cohort
Interventie / Behandeling
Conventional Medical Therapy

Conventional medical therapy as clinically indicated, including somatostatin analogues (octreotide or lanreotide), molecular targeted therapy (everolimus, sunitinib), peptide receptor radionuclide therapy (177Lu-DOTATATE, when available), and/or transarterial locoregional therapy (TACE/TAE). This therapy constitutes the background treatment for both cohorts.
Other

Conventional medical therapy as clinically indicated, including somatostatin analogues (octreotide or lanreotide), molecular targeted therapy (everolimus, sunitinib), peptide receptor radionuclide therapy (177Lu-DOTATATE, when available), and/or transarterial locoregional therapy (TACE/TAE). This therapy constitutes the background treatment for both cohorts. This group of patients is willing to undergo a liver transplant.
Procedure: Liver Transplantation

Deceased-donor or living-donor liver transplantation performed at Tianjin First Central Hospital on the basis of conventional medical therapy.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
5-Year Overall Survival
Tijdsspanne: Up to 5 years after enrollment

Time from enrollment to death from any cause, assessed up to 5 years after enrollment. OS will be estimated by the Kaplan-Meier method and compared between groups using the log-rank test.
Up to 5 years after enrollment

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Overall Survival Rate at 1 Year
Tijdsspanne: 1 year after enrollment

Percentage of participants alive at 1 year after enrollment, estimated by the Kaplan-Meier method.
1 year after enrollment
Overall Survival Rate at 3 Years
Tijdsspanne: 3 years after enrollment

Percentage of participants alive at 3 years after enrollment, estimated by the Kaplan-Meier method.
3 years after enrollment
Progression-Free Survival
Tijdsspanne: Up to 5 years after enrollment

Time from enrollment to radiological progression (per RECIST 1.1) or death from any cause, whichever occurs first, assessed in the conventional medical therapy group.
Up to 5 years after enrollment
Post-transplant Disease-Free Survival
Tijdsspanne: Up to 5 years after liver transplantation

Time from liver transplantation to first radiological recurrence or death from any cause, whichever occurs first, assessed in the liver transplantation group.
Up to 5 years after liver transplantation
Recurrence Pattern After Liver Transplantation
Tijdsspanne: Up to 5 years after liver transplantation

Anatomic pattern of first recurrence, categorized as intrahepatic (graft) recurrence or extrahepatic recurrence.
Up to 5 years after liver transplantation
Treatment-Related Adverse Events
Tijdsspanne: Up to 5 years after enrollment

Percentage of participants experiencing treatment-emergent adverse events, graded by severity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, including post-transplant surgical complications, graft-related events, and systemic drug toxicities.
Up to 5 years after enrollment
Quality of Life Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life Score
Tijdsspanne: Baseline, 6 months, 1 year, and annually thereafter up to 5 years

The EORTC QLQ-C30 global health status/quality of life subscale score ranges from 0 to 100, with higher scores indicating better quality of life.
Baseline, 6 months, 1 year, and annually thereafter up to 5 years
Total Direct Medical Costs
Tijdsspanne: Up to 5 years after enrollment

Total direct medical costs attributable to the treatment course, including surgery, hospitalization, systemic therapy, and management of adverse events, reported in Chinese Yuan (CNY).
Up to 5 years after enrollment
Exploratory Prognostic Value of Ki-67 Proliferation Index
Tijdsspanne: Baseline

Ki-67 proliferation index (percentage of positively stained tumor cell nuclei) assessed by immunohistochemistry on tumor tissue; ranges from 0% to 100%, with higher values indicating higher proliferative activity.
Baseline
Exploratory Prognostic Value of Serum Chromogranin A
Tijdsspanne: Baseline, every 3 months up to 5 years

Serum chromogranin A concentration measured by immunoassay, reported in ng/mL; higher values may indicate greater tumor burden.
Baseline, every 3 months up to 5 years
Exploratory Prognostic Value of NETest Multigene Blood-Based Biomarker Score
Tijdsspanne: Baseline, every 6 months up to 5 years

NETest multigene assay score based on circulating neuroendocrine tumor transcripts, reported as a normalized score from 0 to 100, with higher scores indicating more active disease.
Baseline, every 6 months up to 5 years
Neuroendocrine Tumor-Specific Symptoms Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Neuroendocrine and Gastrointestinal Tumors (EORTC QLQ-GINET21) Score
Tijdsspanne: Baseline, 6 months, 1 year, and annually thereafter up to 5 years

The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Neuroendocrine and Gastrointestinal Tumors (EORTC QLQ-GINET21) score ranges from a minimum of 0 to a maximum of 100, with higher scores indicating a greater burden of disease-specific symptoms, i.e., a worse outcome.
Baseline, 6 months, 1 year, and annually thereafter up to 5 years

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Chiyi Chen

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

1 januari 2019

Primaire voltooiing (Geschat)

31 december 2028

Studie voltooiing (Geschat)

31 december 2028

Studieregistratiedata

Eerst ingediend

22 oktober 2026

Eerst ingediend dat voldeed aan de QC-criteria

28 oktober 2026

Eerst geplaatst (Werkelijk)

3 november 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

3 november 2026

Laatste update ingediend die voldeed aan QC-criteria

28 oktober 2026

Laatst geverifieerd

1 oktober 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • TRANET-GEP-2026-01

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

JA

Beschrijving IPD-plan

Individual de-identified participant data that underlie the results of this study (baseline characteristics, survival outcomes, and adverse event data) will be shared. The study protocol and statistical analysis plan will also be available. Data will be shared with qualified researchers upon reasonable request, after approval of a data use proposal by the study steering committee and the ethics committees of both participating institutions, and after publication of the primary results. Proposals should be directed to the corresponding principal investigator; requests will be reviewed within 3 months. Data will be available for 5 years following article publication.

IPD delen Ondersteunend informatietype

  • LEERPROTOCOOL

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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