Paclitaxel Eluting Covered Metallic Stent for Unresectable Malignant Bile Duct Obstruction

Sponsor

Asan Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00453076

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary goal is to determine stent patency and overall survival of the conventional covered self expandable metallic stent versus paclitaxel eluting covered self expandable metallic stent in unresectable malignant bile duct stricture.

The secondary goals are to assess reinterventions, complications, technical difficulties, and physician graded ease of placement and to assess toxicity of paclitaxel eluting covered self expandable metallic stent.

Condition or Disease	Intervention/Treatment	Phase
Bile Duct Obstruction	Device: Paclitaxel eluting covered metal stent and control covered metal stent	Phase 3

Detailed Description

1.1 Self-expandable metallic stent (SEMS) Self-expandable metallic stent (SEMS) placement is a well-established and widely used treatment for patients with unresectable malignant biliary obstruction. This palliative technique prolongs survival, shortens hospital stay, and improves quality of life in patients with unresectable malignant biliary obstruction. Unfortunately, SEMS have the disadvantage of occlusion over time because of tumor ingrowth (tumor invasion through the metal wire mesh of the stent) or overgrowth (tumor growing at the end of the stent), and mucosal hyperplasia as a consequence of chronic irritation. The occlusion rate of SEMS varies from 10% to 50% of cases of malignant biliary obstruction. 6-9 Duration of SEMS patency is important for patients with a short life-expectancy because quality of life and cost-effectiveness are mainly determined by stent occlusion. Previous studies have suggested that covered metallic stents may prevent tumor ingrowth and reduce the occlusion rate, but tumor overgrowth is still problematic. 11 12 13 Therefore, there is a dire need for a metallic stent that prevents both tumor ingrowth and overgrowth.

1.2. Paclitaxel Paclitaxel is a potent antineoplastic drug extracted from the bark of the pacific yew (Taxus brevifolia) and has been utilized for the therapy for ovarian, breast, lung, and other cancers. This potent drug exerts its pharmacological effects through a unique mechanism. Paclitaxel causes formation of numerous decentralized and unorganized microtubules and enhances the assembly of extraordinarily stable and dysfunctional microtubules. In addition, it inhibits activation processes like activation of protein kinases or release of transcription factors. In addition, paclitaxel has several pharmacokinetic characteristics that make it well suited for locoregional cancer therapy. It has rapid cellular uptake and a first pass effect because of its extremely lipophilic character and long lasting action over a broad concentration range. Furthermore, paclitaxel has antiangiogenic and antimetastatic properties. The efficacy in dose dependent inhibition of cell proliferation of human gallbladder epithelial cells, fibroblasts, and pancreatic adenocarcinoma cells makes paclitaxel a very promising substance for local drug delivery to reduce the proliferative and migratory components that are involved in tumor growth. This inhibitory effect of paclitaxel on the cell lines had served as the basis to develop drug-eluting stents for malignant biliary strictures.

1.3. Paclitaxel-eluting covered metallic stent Covering the stent with chemotherapeutic agent, such as paclitaxel, should give protection against tumor ingrowth, overgrowth, or both resulting in increased patency, longer survival rates and increased remaining quality of life. There had been only few studies on the effect of a paclitaxel-eluting covered metallic stent on animal bile duct. In a study on porcine bile duct, the degree of histologic changes, which included inflammatory cell infiltration and fibrous reactions, corresponded to the amount of paclitaxel incorporated within the stent. The degree of inflammatory change was more severe in porcine bile duct in contact with the stent with 20% concentration (% wt/v) of paclitaxel than the stent with 10% concentration. There was no case of transmural necrosis and perforation. The results of this particular study had served as a basis for further research. In our preliminary study, no significant complications such as perforation or stent migration have occurred in either DDS or CS group. Therefore, it can be suggested that this paclitaxel-eluting SEMS is safe in the normal canine bile duct.

Study Design

Study Type:

Interventional

Actual Enrollment :

52 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomized Trial of Conventional Covered Self Expandable Metallic Stent Versus Paclitaxel Eluting Covered Self Expandable Metallic Stent in Unresectable Malignant Bile Duct Obstruction

Study Start Date :

Nov 1, 2006

Actual Primary Completion Date :

Jun 1, 2008

Actual Study Completion Date :

Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Paclitaxel eluting covered metal stent Paclitaxel eluting covered metal stent group	Device: Paclitaxel eluting covered metal stent and control covered metal stent Paclitaxel eluting covered metal stent and control covered metal stent are inserted with standard ERCP technique
Active Comparator: Control covered metal stent Control covered metal stent group	Device: Paclitaxel eluting covered metal stent and control covered metal stent Paclitaxel eluting covered metal stent and control covered metal stent are inserted with standard ERCP technique

Arm

Intervention/Treatment

Experimental: Paclitaxel eluting covered metal stent

Paclitaxel eluting covered metal stent group

Device: Paclitaxel eluting covered metal stent and control covered metal stent

Paclitaxel eluting covered metal stent and control covered metal stent are inserted with standard ERCP technique

Active Comparator: Control covered metal stent

Control covered metal stent group

Device: Paclitaxel eluting covered metal stent and control covered metal stent

Paclitaxel eluting covered metal stent and control covered metal stent are inserted with standard ERCP technique

Outcome Measures

Primary Outcome Measures

The primary goal is to determine stent patency and overall survival of the conventional covered self expandable metallic stent versus paclitaxel eluting covered self expandable metallic stent in unresectable malignant bile duct stricture. [Two year]

Secondary Outcome Measures

The secondary goals are to assess reinterventions, complications, technical difficulties, and physician graded ease of placement and to assess toxicity of paclitaxel eluting covered self expandable metalic stent. [Two year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Unresectable malignancy of the extrahepatic bile duct
Age >= 18 years and above
Estimated life expectancy of more than 3 months
ECOG performance status of 2 or lower
Adequate bone marrow function
WBCs > 4,000/µL, absolute neutrophil count [ANC]>1,500/µL
Hemoglobin >9.0 g/dL
Platelets > 100,000/µL
Adequate kidney function (creatinine<1.5 mg/dL)
No serious medical or psychological condition that would preclude study treatment
Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Exclusion Criteria:

Age below 18 years
Pregnancy
Active alcohol or drug abuse
Simultaneously participating in another investigational drug or device study
Allergy to stainless steel or nitinol
Allergy to paclitaxel

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Asan Medical Center	Seoul		Korea, Republic of

Sponsors and Collaborators

Asan Medical Center

Investigators

Study Chair: Myung-Hwan Kim, MD,PhD, Asan Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT00453076

Other Study ID Numbers:

2007-11

First Posted:

Mar 28, 2007

Last Update Posted:

Jun 11, 2010

Last Verified:

Nov 1, 2006

Keywords provided by , ,

Biliary Obstruction

Additional relevant MeSH terms:

Cholestasis

Paclitaxel

Study Results

No Results Posted as of Jun 11, 2010