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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00730483
First received: August 7, 2008
Last updated: May 21, 2014
Last verified: May 2014

August 7, 2008
May 21, 2014
February 2009
December 2014   (final data collection date for primary outcome measure)
  • Tumor response (efficacy) [ Time Frame: Time to progression ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: 30 days post study exit ] [ Designated as safety issue: Yes ]
  • Tumor response (efficacy) [ Designated as safety issue: No ]
  • Safety [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00730483 on ClinicalTrials.gov Archive Site
  • Survival [ Time Frame: overall survival ] [ Designated as safety issue: No ]
  • Biochemical response [ Time Frame: Time to progression ] [ Designated as safety issue: No ]
  • Symptomatic response [ Time Frame: Time to progression ] [ Designated as safety issue: No ]
  • Survival [ Designated as safety issue: No ]
  • Biochemical response [ Designated as safety issue: No ]
  • Symptomatic response [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Doxorubicin Beads in Treating Patients With Unresectable Liver Metastases From Neuroendocrine Tumors
Treatment of Patients With Hepatic Neuroendocrine Metastases Using Drug-Eluting Bead Embolization

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.

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.

Interventional
Not Provided
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Gastrointestinal Carcinoid Tumor
  • Islet Cell Tumor
  • Metastatic Cancer
Drug: PVA microporous hydrospheres/doxorubicin hydrochloride
Experimental: single arm
Intervention: Drug: PVA microporous hydrospheres/doxorubicin hydrochloride
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
30
June 2015
December 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
United States
 
NCT00730483
J0739 CDR0000601054, JHOC-J7039, JHOC-NA_000010736, JHOC-SKCCC-J7039
Not Provided
Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Jeffrey F. Geschwind, MD Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP