Liver Transplantation Versus Conventional Medical Therapy for Low-Grade GEP-NET With Liver Metastases (TRANET-GEP)
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
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
連絡先と場所
研究場所
-
-
Tianjin Municipality
-
Tianjin、Tianjin Municipality、中国、300192
- Tianjin Firsr Central Hospital
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
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.
説明
Inclusion Criteria:
- Age 18-70 years at enrollment.
- Histologically confirmed, well-differentiated (G1 or G2) gastroenteropancreatic neuroendocrine tumor (pancreatic or midgut/hindgut primary).
- Unresectable, liver-dominant metastatic disease (multifocal/bilobar involvement not amenable to curative resection or ablation).
- Ki-67 proliferation index ≤ 10% at the most recent biopsy, with stable disease for at least 6 months on standard therapy.
- Primary tumor resected, or resectable/planned for resection as part of the treatment strategy.
- No uncontrolled extrahepatic metastatic disease.
- ECOG performance status 0-1.
- Treatment group assigned by patient/family preference after balanced multidisciplinary counseling; both options (transplantation vs conventional therapy) medically feasible and discussed.
- Written informed consent.
Exclusion Criteria:
- Poorly differentiated neuroendocrine carcinoma (G3, Ki-67 above threshold) or mixed neuroendocrine/non-neuroendocrine neoplasm (MiNEN).
- Uncontrolled extrahepatic metastases or progressive disease despite adequate systemic therapy at enrollment.
- 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.
- Pregnancy or lactation.
- Other active malignancy within the past 5 years (except adequately treated non-melanoma skin cancer or cervical carcinoma in situ).
- Inability or unwillingness to comply with protocol follow-up.
- Participation in another interventional clinical trial with potential interference with endpoints.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 観測モデル：COHORT
- 時間の展望：PROSPECTIVE
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
|
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. |
Deceased-donor or living-donor liver transplantation performed at Tianjin First Central Hospital on the basis of conventional medical therapy. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
5-Year Overall Survival
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Overall Survival Rate at 1 Year
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
|
協力者と研究者
スポンサー
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- TRANET-GEP-2026-01
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
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 共有サポート情報タイプ
- STUDY_PROTOCOL
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。