Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2018

Open Access 01-12-2018 | Study protocol

Randomized Embolization Trial for NeuroEndocrine Tumor Metastases to the Liver (RETNET): study protocol for a randomized controlled trial

Authors: James X. Chen, E. Paul Wileyto, Michael C. Soulen

Published in: Trials | Issue 1/2018

Login to get access

Abstract

Background

Neuroendocrine tumors (NETs) are the second most common gastrointestinal malignancy after colon cancer. Up to 90% of patients with NETs develop liver metastases, which are a major determinant of symptoms and survival. Current guidelines recommend embolotherapy for progressive or symptomatic NET liver metastases, but the optimal technique among bland embolization, lipiodol chemoembolization, and drug-eluting bead chemoembolization remains unknown and controversial.

Methods/design

A prospective, open-label, multicenter randomized controlled trial will be conducted in patients with progressive or symptomatic unresectable NET liver metastases. Patients will be randomized to treatment with bland embolization, lipiodol chemoembolization, or drug-eluting microsphere chemoembolization, with 60 enrollees per arm. The primary endpoint will be hepatic progression-free survival (HPFS) following initial embolotherapy by RECIST criteria. The sample size is powered to detect an HR of 1.78 for HPFS following chemoembolization compared with bland embolization, which was estimated on the basis of existing retrospective studies. Secondary endpoints include overall progression-free survival, duration of symptom control, quality of life, rate of adverse events, and interval between embolotherapy cycles. Interim safety analyses will be performed at 10 and 30 patients per arm.

Discussion

The RETNET trial is a prospective, multicenter randomized controlled trial designed to determine the optimal embolotherapy technique for NET liver metastases.

Trial registration

ClinicalTrials.gov, NCT02724540. Registered on March 31, 2016.
Appendix
Available only for authorised users
Literature
1.
Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A, Evans DB. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26:3063–72.CrossRefPubMed
2.
Chamberlain RS, Canes D, Brown KT, Saltz L, Jarnagin W, Fong Y, Blumgart LH. Hepatic neuroendocrine metastases: does intervention alter outcomes? J Am Coll Surg. 2000;190:432–45.CrossRefPubMed
3.
Barbier CE, Garske-Roman U, Sandstrom M, Nyman R, Granberg D. Selective internal radiation therapy in patients with progressive neuroendocrine liver metastases. Eur J Nucl Med Mol Imaging. 2016;43:1425–31.CrossRefPubMed
4.
Dong XD, Carr BI. Hepatic artery chemoembolization for the treatment of liver metastases from neuroendocrine tumors: a long-term follow-up in 123 patients. Med Oncol. 2011;28(Suppl 1):S286–90.CrossRefPubMed
5.
Fiore F, Del Prete M, Franco R, Marotta V, Ramundo V, Marciello F, Di Sarno A, Carratu AC, de Luca di Roseto C, Colao A, Faggiano A. Transarterial embolization (TAE) is equally effective and slightly safer than transarterial chemoembolization (TACE) to manage liver metastases in neuroendocrine tumors. Endocrine. 2014;47:177–82.CrossRefPubMed
6.
Gupta S, Johnson MM, Murthy R, Ahrar K, Wallace MJ, Madoff DC, McRae SE, Hicks ME, Rao S, Vauthey JN, et al. Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors: variables affecting response rates and survival. Cancer. 2005;104:1590–602.CrossRefPubMed
7.
Memon K, Lewandowski RJ, Riaz A, Salem R. Chemoembolization and radioembolization for metastatic disease to the liver: available data and future studies. Curr Treat Options in Oncol. 2012;13:403–15.CrossRef
8.
Pericleous M, Caplin ME, Tsochatzis E, Yu D, Morgan-Rowe L, Toumpanakis C. Hepatic artery embolization in advanced neuroendocrine tumors: efficacy and long-term outcomes. Asia Pac J Clin Oncol. 2016;12:61–9.CrossRefPubMed
9.
Ruutiainen AT, Soulen MC, Tuite CM, Clark TW, Mondschein JI, Stavropoulos SW, Trerotola SO. Chemoembolization and bland embolization of neuroendocrine tumor metastases to the liver. J Vasc Interv Radiol. 2007;18:847–55.CrossRefPubMed
10.
Sofocleous CT, Petre EN, Gonen M, Reidy-Lagunes D, Ip IK, Alago W, Covey AM, Erinjeri JP, Brody LA, Maybody M, et al. Factors affecting periprocedural morbidity and mortality and long-term patient survival after arterial embolization of hepatic neuroendocrine metastases. J Vasc Interv Radiol. 2014;25:22–30. quiz 31CrossRefPubMed
11.
Sommer WH, Ceelen F, Garcia-Albeniz X, Paprottka PM, Auernhammer CJ, Armbruster M, Nikolaou K, Haug AR, Reiser MF, Theisen D. Defining predictors for long progression-free survival after radioembolisation of hepatic metastases of neuroendocrine origin. Eur Radiol. 2013;23:3094–103.CrossRefPubMed
12.
Strosberg JR, Choi J, Cantor AB, Kvols LK. Selective hepatic artery embolization for treatment of patients with metastatic carcinoid and pancreatic endocrine tumors. Cancer Control. 2006;13:72–8.CrossRefPubMed
13.
Bhagat N, Reyes DK, Lin M, Kamel I, Pawlik TM, Frangakis C, Geschwind JF. Phase II study of chemoembolization with drug-eluting beads in patients with hepatic neuroendocrine metastases: high incidence of biliary injury. Cardiovasc Intervent Radiol. 2013;36:449–59.CrossRefPubMed
14.
Boudreaux JP, Klimstra DS, Hassan MM, Woltering EA, Jensen RT, Goldsmith SJ, Nutting C, Bushnell DL, Caplin ME, Yao JC, North American Neuroendocrine Tumor Society (NANETS). The NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumors of the jejunum, ileum, appendix, and cecum. Pancreas. 2010;39:753–66.CrossRefPubMed
15.
Kennedy A, Bester L, Salem R, Sharma RA, Parks RW, Ruszniewski P, NET-Liver-Metastases Consensus Conference. Role of hepatic intra-arterial therapies in metastatic neuroendocrine tumours (NET): guidelines from the NET-Liver-Metastases Consensus Conference. HPB (Oxford). 2015;17:29–37.CrossRef
16.
Kulke MH, Anthony LB, Bushnell DL, de Herder WW, Goldsmith SJ, Klimstra DS, Marx SJ, Pasieka JL, Pommier RF, Yao JC, et al. NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas. 2010;39:735–52.CrossRefPubMedPubMedCentral
17.
Kulke MH, Shah MH, Benson AB 3rd, Bergsland E, Berlin JD, Blaszkowsky LS, Emerson L, Engstrom PF, Fanta P, Giordano T, et al. Neuroendocrine tumors, version 1.2015. J Natl Compr Cancer Netw. 2015;13:78–108.CrossRef
18.
Pavel M, Baudin E, Couvelard A, Krenning E, Oberg K, Steinmuller T, Anlauf M, Wiedenmann B, Salazar R, Barcelona Consensus Conference participants. ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology. 2012;95:157–76.CrossRefPubMed
19.
Pitt SC, Knuth J, Keily JM, McDermott JC, Weber SM, Chen H, Rilling WS, Quebbeman EJ, Agarwal DM, Pitt HA. Hepatic neuroendocrine metastases: chemo- or bland embolization? J Gastrointest Surg. 2008;12:1951–60.CrossRefPubMedPubMedCentral
20.
Maire F, Lombard-Bohas C, O’Toole D, Vullierme MP, Rebours V, Couvelard A, Pelletier AL, Zappa M, Pilleul F, Hentic O, et al. Hepatic arterial embolization versus chemoembolization in the treatment of liver metastases from well-differentiated midgut endocrine tumors: a prospective randomized study. Neuroendocrinology. 2012;96:294–300.CrossRefPubMed
21.
Ho AS, Picus J, Darcy MD, Tan B, Gould JE, Pilgram TK, Brown DB. Long-term outcome after chemoembolization and embolization of hepatic metastatic lesions from neuroendocrine tumors. AJR Am J Roentgenol. 2007;188:1201–7.CrossRefPubMed
22.
Guiu B, Deschamps F, Aho S, Munck F, Dromain C, Boige V, Malka D, Leboulleux S, Ducreux M, Schlumberger M, et al. Liver/biliary injuries following chemoembolisation of endocrine tumours and hepatocellular carcinoma: lipiodol vs. drug-eluting beads. J Hepatol. 2012;56:609–17.CrossRefPubMed
23.
Gaba RC. Chemoembolization practice patterns and technical methods among interventional radiologists: results of an online survey. AJR Am J Roentgenol. 2012;198:692–9.CrossRefPubMed
24.
Vinik E, Silva MP, Vinik AI. Measuring the relationship of quality of life and health status, including tumor burden, symptoms, and biochemical measures in patients with neuroendocrine tumors. Endocrinol Metab Clin N Am. 2011;40:97–109. viiiCrossRef
25.
Gaba RC, Lokken RP, Hickey RM, Lipnik AJ, Lewandowski RJ, Salem R, Brown DB, Walker TG, Silberzweig JE, Baerlocher MO, et al. Quality improvement guidelines for transarterial chemoembolization and embolization of hepatic malignancy. J Vasc Interv Radiol. 2017;28:1210–1223.e3.CrossRefPubMed
26.
Liu PY, Moon J, LeBlanc M. Phase II selection designs. In Crowley J, Ankerst DP, editors. Handbook of statistics in clinical oncology. 2nd ed. Boca Raton, FL: Chapman & Hall/CRC; 2006. p. 155–66.
27.
Liu P, Dahlberg S, Crowley J. Selection designs for pilot studies based on survival. Biometrics. 1993;49:391–8.CrossRefPubMed
Metadata
Title
Randomized Embolization Trial for NeuroEndocrine Tumor Metastases to the Liver (RETNET): study protocol for a randomized controlled trial
Authors
James X. Chen
E. Paul Wileyto
Michael C. Soulen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Trials / Issue 1/2018
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-018-2782-5

Other articles of this Issue 1/2018

Trials 1/2018 Go to the issue

Study protocol

Balancing ACT: evaluating the effectiveness of psychoeducation and Acceptance and Commitment Therapy (ACT) groups for people with bipolar disorder: study protocol for pilot randomised controlled trial

Study protocol

Improving pain treatment with a smartphone app: study protocol for a randomized controlled trial

Study protocol

Continuous versus intermittent endotracheal cuff pressure control for the prevention of ventilator-associated respiratory infections in Vietnam: study protocol for a randomised controlled trial

Study protocol

Percutaneous transhepatic vs. endoscopic retrograde biliary drainage for suspected malignant hilar obstruction: study protocol for a randomized controlled trial

Study protocol

Xue-Fu-Zhu-Yu capsule in the treatment of qi stagnation and blood stasis syndrome: a study protocol for a randomised controlled pilot and feasibility trial

Study protocol

Efficacy of pre-operative quadriceps strength training on knee-extensor strength before and shortly following total knee arthroplasty: protocol for a randomized, dose-response trial (The QUADX-1 trial)