Clinical trial NCT00730483: Doxorubicin Beads in Treating Patients With Unresectable Liver Metastases From Neuroendocrine Tumors
Official title: Treatment of Patients With Hepatic Neuroendocrine Metastases Using Drug-Eluting Bead Embolization
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Gastrointestinal Carcinoid Tumor
Islet Cell Tumor
Metastatic Cancer
Keywords: liver metastases
metastatic gastrointestinal carcinoid tumor
regional gastrointestinal carcinoid tumor
islet cell carcinoma
gastrinoma
insulinoma
glucagonoma
pancreatic polypeptide tumor
somatostatinoma
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-08-08
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE
timeFrame: 1 month after initial DEB-TACE treatment
Secondary outcomes:
measure: Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria
timeFrame: 12 months
measure: Survival
timeFrame: overall survival
measure: Biochemical Response - Time to Progression
timeFrame: Time to progression, 12 months
measure: Symptomatic Response by Assessing Symptom Severity in Patients
timeFrame: Duration of study participation, average of 12 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Jeffrey F. Geschwind, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.