Doxorubicin Beads in Treating Patients With Unresectable Liver Metastases From Neuroendocrine Tumors

NCT ID: NCT00730483

Last Updated: 2017-08-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2014-06-30

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Infusing doxorubicin beads into the liver, and blocking blood flow to the tumor, may keep doxorubicin near the tumor and kill more tumor cells.

PURPOSE: This clinical trial is studying the side effects of doxorubicin beads and to see how well they work in treating patients with unresectable liver metastases from neuroendocrine tumors.

Detailed Description

OBJECTIVES:

Primary

• To gather preliminary data and determine the feasibility of a randomized study of patients with unresectable hepatic neuroendocrine metastases using PVA microporous hydrospheres/doxorubicin hydrochloride.

OUTLINE: A catheter is placed into the right or left hepatic artery. Patients with unifocal tumors will have the catheter or microcatheter placed more selectively into the 2nd or 3rd order branch off the right or left hepatic artery in closer proximity to the tumor. Polyvinyl alcohol (PVA) microporous hydrospheres/doxorubicin hydrochloride mixture is injected into the delivery area.

Patients with less than 75% necrosis at 1 month undergo a second (and possibly a third a month later) chemoembolization.

After completion of study therapy, patients are followed at 1 month, every 2 months for 1 year, and then every 3 months for 1 year.

Conditions

Gastrointestinal Carcinoid Tumor; Islet Cell Tumor; Metastatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DEB-TACE

PVA microporous hydrospheres loaded with doxorubicin hydrochloride used for the treatment of unresectable liver metastases from neuroendocrine tumors.

Group Type: EXPERIMENTAL

PVA microporous hydrospheres/doxorubicin hydrochloride

Intervention Type: DRUG

Interventions

PVA microporous hydrospheres/doxorubicin hydrochloride

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosis of hepatic neuroendocrine metastases not suitable for radical therapies (e.g., resection or liver transplantation)

• Histologically proven neuroendocrine tumor
• Tumors are hypervascular based on visual estimation by investigator
• Predominant to the liver disease, but extrahepatic disease is not an exclusion

• No predominant extrahepatic liver disease
• No significant life-threatening extrahepatic disease, in the judgment of the physician
• Recent-interval progression of hepatic liver metastases
• No diffuse hepatic neuroendocrine metastases defined as massive ill-defined tumor involvement measuring > 90% tumor burden

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Must have preserved liver function (Child-Pugh class A-B) without significant liver decompensation

• No advanced liver disease (e.g., Child-Pugh C class or active gastrointestinal bleeding, encephalopathy, or ascites [trace ascites is acceptable]), meeting the following criteria:

• Bilirubin > 3 mg/dL
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase > 5 times upper limit of normal
• Serum creatinine > 2.0 mg/dL
• Albumin ≤ 2.0 g/dL
• No vascular anatomy or blood that precludes catheter placement or emboli injection
• No presence of arteries supplying the lesion not large enough to accept PVA microporous hydrospheres/doxorubicin hydrochloride
• No collateral vessel pathways potentially endangering normal territories during embolization
• No feeding arteries smaller than distal branches from which they emerge
• Not pregnant

Exclusion Criteria

• Clinically evident ascites (a radiographic finding of trace ascites on imaging is acceptable)
• Complete occlusion of the entire portal venous system
• Evidence of cirrhosis or portal hypertension
• Vascular resistance peripheral to the feeding arteries precluding passage of PVA microporous hydrospheres/doxorubicin hydrochloride

PATIENT CHARACTERISTICS:

• See Disease Characteristics
• Another active primary tumor
• Any contraindication for hepatic embolization procedures, including any of the following:

• Porto-systemic shunt
• Hepatofugal blood flow
• Impaired clotting tests (i.e., platelet count < 50,000/mm³, international normalized ratio (INR) ≥ 1.8, or partial thromboplastin time (PTT) ≥ 39 seconds)
• Renal failure
• Severe peripheral vascular disease precluding catheterization
• Any contraindication for doxorubicin hydrochloride administration (i.e., serum bilirubin > 5 mg/dL or leukocyte count < 1,500 cells/mm³)
• Allergy to contrast media
• Intolerant to occlusion procedures
• Presence of end arteries leading directly to cranial nerves
• Presence or likely onset of hemorrhage
• Presence of severe atheromatous disease

PRIOR CONCURRENT THERAPY:

• Prior anticancer therapy for hepatic neuroendocrine metastases, except previous surgical therapy
• Any continuing complication or prior cancer therapy that has not improved or resolved prior to 21 days before start of treatment, if the investigator determines that the continuing complication will compromise the safety of the patient after treatment with PVA microporous hydrospheres/doxorubicin hydrochloride
• Presence of patent extra-to-intracranial anastomoses or shunts
• Use of PVA microporous hydrospheres/doxorubicin hydrochloride in the following applications:

• Embolization of large-diameter arteriovenous shunts
• Pulmonary arterial vasculature
• Any vasculature where the use of PVA microporous hydrospheres/doxorubicin hydrochloride could pass directly into the internal carotid artery or the above-listed vessels
• Concurrent enrollment in another clinical study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Jeff Geschwind

Professor of Radiology and Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey F. Geschwind, MD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

References

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 Apr;36(2):449-59. doi: 10.1007/s00270-012-0424-y. Epub 2012 Jun 22.

Reference Type: DERIVED

PMID: 22722717 (View on PubMed)

Other Identifiers

JHOC-J7039

Identifier Type: -

Identifier Source: secondary_id

JHOC-NA_000010736

Identifier Type: -

Identifier Source: secondary_id

JHOC-SKCCC-J7039

Identifier Type: -

Identifier Source: secondary_id

J0739 CDR0000601054

Identifier Type: -

Identifier Source: org_study_id