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

Metastatic Cancer Clinical Trial

Official title:

Treatment of Patients With Hepatic Neuroendocrine Metastases Using Drug-Eluting Bead Embolization

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00730483
• Other study ID #: J0739 CDR0000601054
• Secondary ID: JHOC-J7039JHOC-N
• Status: Active, not recruiting
• Phase: N/A
• First received: August 7, 2008
• Last updated: October 1, 2014
• Start date: February 2009
• Est. completion date: June 2015

Study information

• Verified date: October 2014
• Source: Sidney Kimmel Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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. 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: June 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

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

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:

Inclusion criteria:

• 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

• AST, 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:

• 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, INR = 1.8, or 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:

Exclusion criteria:

• 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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoid Tumor
• Gastrointestinal Carcinoid Tumor
• Gastrointestinal Neoplasms
• Islet Cell Tumor
• Malignant Carcinoid Syndrome
• Metastatic Cancer
• Neoplasm Metastasis
• Neoplasms
• Neuroendocrine Tumors

Intervention

Drug:
• PVA microporous hydrospheres/doxorubicin hydrochloride

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor response (efficacy)		Time to progression	No
Primary	Safety		30 days post study exit	Yes
Secondary	Survival		overall survival	No
Secondary	Biochemical response		Time to progression	No
Secondary	Symptomatic response		Time to progression	No