Randomized Embolization Trial for NeuroEndocrine Tumor Metastases to the Liver

NCT02724540 | Completed Phase 2 DMC

• 1 other identifier: UPCC 01215
• Study Type: interventional
• Target: 162
• Locations: 4 countries
• Sites: 13

Brief Summary

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.

Conditions

Neuroendocrine Tumor, Malignant; Liver Metastases

Outcome Measures

Primary Outcomes (1)

• Abdominal MRI/Triple Phase CT

  Hepatic progression-free interval (H-PFS)

  2 years

Secondary Outcomes (1)

• Number of Adverse Events

  2 years

Study Arms (3)

Arm 1 - BE

EXPERIMENTAL

Lobar or segmental bland embolization (BE) with microspheres (50-500 microns) to 2-5 heartbeat stasis.

Device: Bland Embolization

Arm 2 - TACE

EXPERIMENTAL

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

Arm 3 - DEB - CLOSED

EXPERIMENTAL

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

Interventions

Bland Embolization DEVICE

Lobar or segmental bland embolization with microspheres (50-500 microns) to 2-5 heartbeat stasis

Also known as: BE

Arm 1 - BE

Transarterial chemoembolization COMBINATION_PRODUCT

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.

Also known as: TACE

Arm 2 - TACE

Drug Eluting Beads Embolization COMBINATION_PRODUCT

CLOSED - Lobar or segmental hepatic chemoembolization with DEBDOX (100-300 or 300-500 micron beads loaded with doxorubicin per manufacturer IFU.

Also known as: DEB

Arm 3 - DEB - CLOSED

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• severe allergy or intolerance to contrast media, narcotics, sedatives, or atropine.
• bleeding diathesis not correctable by usual forms of therapy.
• severe peripheral vascular disease precluding catheterization.
• Contraindications to hepatic artery embolization:
• portal vein occlusion without hepatopedal collateral flow demonstrated by angiography; or portal hypertension with hepatofugal flow.
• hepatic encephalopathy.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead
• Guerbet: collaborator

Study Sites (13)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Stanford University

Standford, California, 94305, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Hospital Italiano de Buenos Aires

Buenos Aires, C1191 ABH, Argentina

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N3M5, Canada

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Related Publications (1)

• 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.

  PMID: 30016989 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Study Officials

• Michael C Soulen, MD, FSIR

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2016
• First Posted: March 31, 2016
• Study Start: March 1, 2016
• Primary Completion: April 30, 2024
• Study Completion: November 8, 2024
• Last Updated: January 6, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

AR (1); CA (1); IT (1); US (10)