Randomized Embolization Trial for NeuroEndocrine Tumor Metastases To The Liver

• Sponsor: University of Pennsylvania
• Collaborator: Guerbet
• Information provided by (Responsible Party): University of Pennsylvania

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Neuroendocrine Tumor, Malignant; Liver Metastases	Device: Bland Embolization; Combination Product: Transarterial chemoembolization; Combination Product: Drug Eluting Beads Embolization	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 180 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Randomized Embolization Trial for NeuroEndocrine Tumor Metastases To The Liver
• Study Start Date: March 2016
• Estimated Primary Completion Date: March 2020
• Estimated Study Completion Date: March 2021

Arms and Interventions

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 Name: 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 Name: 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 Name: DEB

Outcome Measures

Primary Outcome Measures :

1. Abdominal MRI/Triple Phase CT [ Time Frame: 2 years ]
   Hepatic progression-free interval (H-PFS)

Secondary Outcome Measures :

1. Number of Adverse Events [ Time Frame: 2 years ]
   Symptom-relief interval and toxicity

Eligibility Criteria

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

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.

Contacts and Locations

Contacts

Contact: Michael C Soulen, MD, FSIR; 855-216-0098; michael.soulen@uphs.upenn.edu

Locations

United States, California

University of California San Francisco; Recruiting

San Francisco, California, United States, 94143

Contact: Nicholas Feldman, MD

Principal Investigator: Nicholas Feldman, MD

Stanford University; Recruiting

Stanford, California, United States, 94305

Contact: Nishita Kothary, MD

Principal Investigator: Nishita Kothary, MD

United States, Florida

Moffitt Cancer Center; Recruiting

Tampa, Florida, United States, 33612

Contact: Ghassan El-Haddad, MD

Principal Investigator: Ghassan El-Haddad, MD

United States, Louisiana

Ochsner Medical Center; Recruiting

Baton Rouge, Louisiana, United States, 70816

Contact: Juan Gimenez, MD

Principal Investigator: Juan Gimenez, MD

United States, Oregon

Oregon Health & Science University; Recruiting

Portland, Oregon, United States, 97239

Contact: Kenneth Kolbeck, MD, PhD

Principal Investigator: Kenneth Kolbeck, MD, PhD

United States, Pennsylvania

Hospital of the University of Pennsylvania; Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contact: Michael C Soulen, MD, FSIR 855-216-0098 michael.soulen@uphs.upenn.edu

Principal Investigator: Michael C Soulen, MD, FSIR

United States, Texas

MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Contact: Rony Avritscher, MD

Principal Investigator: Rony Avritscher, MD

United States, Wisconsin

Medical College of Wisconsin; Recruiting

Milwaukee, Wisconsin, United States, 53226

Contact: Sarah B White, MD, MS

Principal Investigator: Sarah B White, MD, MS

Argentina

Hospital Italiano de Buenos Aires; Recruiting

Buenos Aires, Argentina, C1191 ABH

Contact: Ricardo Monaco-Garcia, MD

Principal Investigator: Ricardo Monaco-Garcia, MD

Sponsors and Collaborators

University of Pennsylvania

Guerbet

Investigators

• Principal Investigator: Michael C Soulen, MD, FSIR; University of Pennsylvania

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT02724540 History of Changes
• Other Study ID Numbers: UPCC 01215
• First Posted: March 31, 2016
• Last Update Posted: March 19, 2019
• Last Verified: March 2019

Additional relevant MeSH terms:

Neoplasm Metastasis; Neuroendocrine Tumors; Neoplastic Processes; Neoplasms; Pathologic Processes; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Doxorubicin; Liposomal doxorubicin; Antibiotics, Antineoplastic; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action