Randomized Embolization Trial for NeuroEndocrine Tumor Metastases To The Liver

The primary aim of this trial is to estimate the duration of hepatic progression-free survival (HPFS) in participants treated with bland embolization (BE), transcatheter arterial Lipiodol chemoembolization (TACE), and embolization by drug-eluting beads (DEB). The primary hypothesis is that chemoembolization will be nearly twice as durable as bland embolization; thatis, the hazard ratio for HPFS will be 1.76 or better.

Study Overview

• Status: Active, not recruiting
• Conditions: Liver Metastases; Neuroendocrine Tumor, Malignant
• Intervention / Treatment: Device: Bland Embolization; Combination product: Transarterial chemoembolization; Combination product: Drug Eluting Beads Embolization

• Study Type: Interventional
• Enrollment (Actual): 162
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1191 ABH
    • Hospital Italiano de Buenos Aires
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N3M5
      • SunnyBrook Health Sciences Centre
• Italy
  • Milan, Italy, 20132
    • Ospedale San Raffaele
• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco
    • Stanford, California, United States, 94305
      • Stanford University
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants 18 years and older;
• Biopsy-proven neuroendocrine tumor.
• Measurable metastasis to liver with at least one dimension ≥ 1.0 cm.
• Tumor burden dominant in the liver AND liver tumor burden less than or equal to 70% of the total liver volume by visual estimate.
• Not a candidate for surgical resection based on unresectability, anatomy, anesthesia risk, patient preference.
• Symptoms uncontrolled by somatostatin analogues OR morphologically progressive tumor by RECIST 1.1 criteria in the liver OR baseline tumor burden >25% of the liver volume.
• There must be no plans for the patient to receive other concomitant therapy while on this protocol treatment (other than somatostatin analogs or bone-strengthening agents).
• Performance status 0-2 on Zubrod/ECOG Performance Scale;
• Serum creatinine < 2.0 mg/dL;
• Serum Bilirubin ≤ 2.0 mg/dL
• Serum albumin ≥ 3.0 g/dL
• Platelet count > 50 thousands/uL (corrected if needed)
• INR ≤ 1.5 (corrected if needed)
• All patients must be informed of the investigational nature of this study and must sign a study specific informed consent in accordance with institutional and federal guidelines prior to study entry.

Exclusion Criteria:

• Pregnant or lactating women may not participate due to the embryotoxic effects of protocol treatment. Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• Prior hepatic arterial therapy or hepatic radiation therapy. Prior surgical resection or ablation of liver metastases is acceptable. Patients must be at least one month beyond prior chemotherapy, PRRT, ablation or surgery, and have recovered from all therapy-associated toxicities.
• Active infection (Symptomatic bacterial and fungal infection - newly diagnosed and/or requiring treatment);
• Choledochoenteric anastomosis; transpapillary biliary stent, or sphincterotomy of duodenal papilla
• Absolute contraindication to intravenous iodinated contrast (Hx of significant previous contrast reaction, not mitigated by appropriate pre-medication).

• Contraindications to arteriography and selective visceral catheterization:

  1. severe allergy or intolerance to contrast media, narcotics, sedatives, or atropine.
  2. bleeding diathesis not correctable by usual forms of therapy.
  3. severe peripheral vascular disease precluding catheterization.

• Contraindications to hepatic artery embolization:

  1. portal vein occlusion without hepatopedal collateral flow demonstrated by angiography; or portal hypertension with hepatofugal flow.
  2. hepatic encephalopathy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 - BE; Lobar or segmental bland embolization (BE) with microspheres (50-500 microns) to 2-5 heartbeat stasis.	Device: Bland Embolization; Lobar or segmental bland embolization with microspheres (50-500 microns) to 2-5 heartbeat stasis; Other Names: BE
Experimental: Arm 2 - TACE; Lobar or segmental lipiodol conventional transarterial chemoembolization (TACE). Doxorubicin 50 mg dissolved in 10 mL dilute contrast and emulsified with 10-20 cc iodized oil, followed by 50-500 μm microspheres.	Combination product: Transarterial chemoembolization; Lobar or segmental lipiodol transarterial chemoembolization. Doxorubicin 50 mg dissolved in 10 mL dilute contrast and emulsified with 10-20 cc iodized oil, followed by 50-500 μm microspheres.; Other Names: TACE
Experimental: Arm 3 - DEB - CLOSED; Lobar or segmental hepatic chemoembolization with DEBDOX (100-300 or 300-500 micron beads loaded with doxorubicin per manufacturer IFU monthly until entire tumor burden is treated.	Combination product: Drug Eluting Beads Embolization; CLOSED - Lobar or segmental hepatic chemoembolization with DEBDOX (100-300 or 300-500 micron beads loaded with doxorubicin per manufacturer IFU.; Other Names: DEB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Abdominal MRI/Triple Phase CT	Hepatic progression-free interval (H-PFS)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events	Symptom-relief interval and toxicity	2 years

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Collaborators: Guerbet
• Investigators: Principal Investigator: Michael C Soulen, MD, FSIR, University of Pennsylvania

Publications and helpful links

General Publications

• Chen JX, Wileyto EP, Soulen MC. Randomized Embolization Trial for NeuroEndocrine Tumor Metastases to the Liver (RETNET): study protocol for a randomized controlled trial. Trials. 2018 Jul 17;19(1):390. doi: 10.1186/s13063-018-2782-5.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: March 28, 2016
• First Submitted That Met QC Criteria: March 28, 2016
• First Posted (Estimated): March 31, 2016

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplastic Processes; Neoplasm Metastasis; Neuroendocrine Tumors
• Other Study ID Numbers: UPCC 01215