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

28 octobre 2026 mis à jour par: 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

Aperçu de l'étude

Statut

Inscription sur invitation

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Observationnel

Inscription (Estimé)

100

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 70 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Oui

Sexes éligibles pour l'étude

Tout

Méthode d'échantillonnage

Échantillon de probabilité

Population étudiée

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.

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Modèles d'observation: COHORT
  • Perspectives temporelles: PROSPECTIVE

Cohortes et interventions

Groupe / Cohorte
Intervention / Traitement
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.
Procédure: Liver Transplantation

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

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
5-Year Overall Survival
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Overall Survival Rate at 1 Year
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Chiyi Chen

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

1 janvier 2019

Achèvement primaire (Estimé)

31 décembre 2028

Achèvement de l'étude (Estimé)

31 décembre 2028

Dates d'inscription aux études

Première soumission

22 octobre 2026

Première soumission répondant aux critères de contrôle qualité

28 octobre 2026

Première publication (Réel)

3 novembre 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

3 novembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

28 octobre 2026

Dernière vérification

1 octobre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • TRANET-GEP-2026-01

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

OUI

Description du régime IPD

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.

Type d'informations de prise en charge du partage d'IPD

  • PROTOCOLE D'ÉTUDE

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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