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

This study has been terminated.
(High incidence of biloma and liver abscess after TACE)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00730483
First Posted: August 8, 2008
Last Update Posted: August 25, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jeff Geschwind, Yale University
  Purpose

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.


Condition Intervention
Gastrointestinal Carcinoid Tumor Islet Cell Tumor Metastatic Cancer Drug: PVA microporous hydrospheres/doxorubicin hydrochloride

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Patients With Hepatic Neuroendocrine Metastases Using Drug-Eluting Bead Embolization

Resource links provided by NLM:


Further study details as provided by Jeff Geschwind, Yale University:

Primary Outcome Measures:
  • Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE [ Time Frame: 1 month after initial DEB-TACE treatment ]
    Safety was assessed at each DEB-TACE procedure and at every follow-up thereafter according to National Cancer Institute Common Toxicity Criteria (CTCAE) v3.0. The study was prematurely terminated due to high incidence of biloma and liver abscess. Safety data below is based off of 13 patients enrolled on protocol at 1 month post initial treatment.


Secondary Outcome Measures:
  • Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria [ Time Frame: 12 months ]

    Study was terminated and full outcome not assessed. The results below are based on 13 patients at 1 month post DEB-TACE, 10 patients at 6 months, and 6 patients at 12 months.

    RECIST:

    Complete Response (CR): Disappearance of all targeted lesions Partial Response (PR): At least 30% decrease in the sum of longest diameter (LD) of targeted lesions Progressive Disease (PD): At least 20% increase in the sum of LD of targeted lesions Stable Disease (SD): Cases that are not applicable for PD or PR.

    EASL:

    CR: Absence of any enhancement in target lesion PR: Greater than 50% decrease from baseline enhancement in target lesion PD: Greater than 25% increase in target lesion SD: All other cases


  • Survival [ Time Frame: overall survival ]
    Survival outcomes not assessed due to premature termination of study.

  • Biochemical Response - Time to Progression [ Time Frame: Time to progression, 12 months ]
    Biochemical response not assessed due to premature termination of study.

  • Symptomatic Response by Assessing Symptom Severity in Patients [ Time Frame: Duration of study participation, average of 12 months ]

    Symptomatic response not assessed due to premature termination of study.

    Scoring system for assessing symptom severity in patients with neuroendocrine/carcinoid syndrome was as follows:

    1. - No symptoms - Patient completely asymptomatic
    2. - Mild symptoms - Patient with symptoms of diarrhea, flushing, or asthma up to 4 times weekly
    3. - Symptoms impact daily living - symptoms of diarrhea, flushing, or asthma up 5-7 weekly
    4. - Severe symptoms - multiple daily symptoms of diarrhea, flushing, or asthma; symptoms require significant reorganization of daily activities
    5. - Disabling symptoms - Patient disabled by multiple attacks and severe symptoms; unable to leave home or requires hospitalization


Enrollment: 13
Study Start Date: February 2009
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DEB-TACE
PVA microporous hydrospheres loaded with doxorubicin hydrochloride used for the treatment of unresectable liver metastases from neuroendocrine tumors.
Drug: PVA microporous hydrospheres/doxorubicin hydrochloride

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

  • 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:

  • 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:

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00730483


Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Yale University
National Cancer Institute (NCI)
Investigators
Principal Investigator: Jeffrey F. Geschwind, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jeff Geschwind, Professor of Radiology and Oncology, Yale University
ClinicalTrials.gov Identifier: NCT00730483     History of Changes
Other Study ID Numbers: J0739 CDR0000601054
JHOC-J7039
JHOC-NA_000010736
JHOC-SKCCC-J7039
First Submitted: August 7, 2008
First Posted: August 8, 2008
Results First Submitted: April 19, 2017
Results First Posted: August 25, 2017
Last Update Posted: August 25, 2017
Last Verified: July 2017

Keywords provided by Jeff Geschwind, Yale University:
liver metastases
metastatic gastrointestinal carcinoid tumor
regional gastrointestinal carcinoid tumor
islet cell carcinoma
gastrinoma
insulinoma
glucagonoma
pancreatic polypeptide tumor
somatostatinoma

Additional relevant MeSH terms:
Neoplasms
Neoplasm Metastasis
Carcinoid Tumor
Neuroendocrine Tumors
Malignant Carcinoid Syndrome
Gastrointestinal Neoplasms
Adenoma, Islet Cell
Neoplastic Processes
Pathologic Processes
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Adenoma
Pancreatic Neoplasms
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors


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