Randomized Embolization Trial for NeuroEndocrine Tumor Metastases to the Liver

NCT ID: NCT02724540

Last Updated: 2025-01-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 162 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2024-11-08

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1 - BE

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

Group Type: EXPERIMENTAL

Bland Embolization

Intervention Type: DEVICE

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

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.

Group Type: EXPERIMENTAL

Transarterial chemoembolization

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Drug Eluting Beads Embolization

Intervention Type: COMBINATION_PRODUCT

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

Interventions

Bland Embolization

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

Intervention Type: DEVICE

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.

Intervention Type: 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.

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

BE; TACE; DEB

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guerbet

INDUSTRY

Sponsor Role: collaborator

Abramson Cancer Center at Penn Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael C Soulen, MD, FSIR

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

University of California San Francisco

San Francisco, California, United States

Stanford University

Standford, California, United States

Moffitt Cancer Center

Tampa, Florida, United States

Mount Sinai School of Medicine

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Oregon Health & Science University

Portland, Oregon, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

MD Anderson Cancer Center

Houston, Texas, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Hospital Italiano de Buenos Aires

Buenos Aires, , Argentina

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Ospedale San Raffaele

Milan, , Italy

Countries

United States; Argentina; Canada; Italy

References

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.

Reference Type: DERIVED

PMID: 30016989 (View on PubMed)

Other Identifiers

UPCC 01215

Identifier Type: -

Identifier Source: org_study_id