search
Back to results

Halt Growth of Liver Tumors From Uveal Melanoma With Closure of Liver Artery Following Injection of GM-CSF

Primary Purpose

Uveal Melanoma, Liver Metastases

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
GM-CSF
Embolization
Sponsored by
Sidney Kimmel Cancer Center at Thomas Jefferson University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Uveal Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Metastatic uveal melanoma in the liver with histological confirmation
  • Ability/willingness to give informed consent
  • ECOG performance status of 0 or 1
  • Adequate renal, liver and bone marrow function

Exclusion Criteria:

  • Solitary liver metastasis that is amenable to surgical removal
  • Presence of symptomatic liver failure including ascites and hepatic encephalopathy
  • Presence of extra-hepatic metastases
  • Untreated brain metastases
  • Uncontrolled hypertension or congestive heart failure or acute myocardial infarction within 6 months of entry
  • Presence of any other medical complication that imply survival of less than six months
  • Uncontrolled sever bleeding tendency or active GI bleeding
  • Significant allergic reaction to contrast dye or GM-CSF
  • Immunosuppressive treatments such as systemic steroids, radiation to pelvis or systemic chemotherapy within 4 weeks
  • Previous embolization of the hepatic artery or intrahepatic arterial chemotherapy of liver metastasis
  • Active hepatitis with serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) greater than 5 x normal
  • HIV infection positive by ELISA
  • Pregnancy or breast feeding women
  • Biliary obstruction, biliary stent or prior biliary surgery except cholecystectomy
  • Significant arteriovenous shunt identified on angiography of the hepatic artery
  • Occlusion of main portal vein or inadequate collateral flow around an occluded portal vein

Sites / Locations

  • Thomas Jefferson University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Immunoembolization

Plain embolization

Arm Description

Liver embolization treatment with injection of GM-CSF.

Liver embolization with normal saline injected in place of GM-CSF

Outcomes

Primary Outcome Measures

Response of Liver Metastases
Complete response: Disappearance of all target and non-target liver lesions Partial response: >= 30% decrease in the sum of the longest diameters (LD) relative to baseline sum LD with at least stable non-target liver lesions Stable disease: Absence of change which would qualify as response or progression Progression: >= 20% increase in the sum LD in target liver lesions or unequivocal progression of non-target liver lesions in the treated lobe(s) or appearance of one or more new liver lesions >= 10mm in the treated lobe(s)
Overall Response Rate
Clinical response in the liver metastases will be evaluated after every two embolizations using CT scans or MRI of the abdomen. The sum of the longest diameter (LD) of up to 6 target lesions will be used to determine response. Target indicator lesions will be identified and measured as baseline prior to the first embolization. The same target lesions will then be measured 3 to 4 weeks after every two treatments. The sum of the baseline LDs will be compared to the sum of the LDs after every two treatments.

Secondary Outcome Measures

Overall Survival
Measured from the start of the treatment to death of patients
Median Progression Free Survival
Measured from the start of the treatment to confirmation of progression of disease by either imaging tests or physical examination. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of one or more new liver lesions >= 10mm in the treated lobe(s).
Systemic Progression Free Survival
Measured from the start of the treatment to confirmation of progression of disease by either imaging tests or physical examination. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of one or more new liver lesions >= 10mm in the treated lobe(s).

Full Information

First Posted
April 16, 2008
Last Updated
October 19, 2016
Sponsor
Sidney Kimmel Cancer Center at Thomas Jefferson University
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00661622
Brief Title
Halt Growth of Liver Tumors From Uveal Melanoma With Closure of Liver Artery Following Injection of GM-CSF
Official Title
Immuno-embolization of Hepatic Artery With Granulocyte-macrophage Colony Stimulating Factor (GM-CSF)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
October 2004 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
June 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Cancer Center at Thomas Jefferson University
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Patients with uveal melanoma metastatic to the liver will be treated with embolization of the hepatic artery every 4 weeks. GM-CSF (granulocyte-macrophage colony simulating factor) or normal saline will be injected into one of the liver arteries with an oily contrast dye, Ethiodol. This is followed by blockage of the artery with small pieces of gelatin sponge (embolization). It is hoped with this novel approach that: tumor cells will die due to a loss of their blood supply, local inflammatory reactions induced by GM-CSF will kill remaining tumor cells, and a systemic immune response against tumor cells may develop.
Detailed Description
Patients with uveal melanoma metastatic to the liver will be treated with embolization of the hepatic artery every 4 weeks. GM-CSF (granulocyte-macrophage colony simulating factor) or normal saline will be injected into one of the liver arteries with an oily contrast dye, Ethiodol. This is followed by blockage of the artery with small pieces of gelatin sponge (embolization).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Uveal Melanoma, Liver Metastases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
53 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Immunoembolization
Arm Type
Experimental
Arm Description
Liver embolization treatment with injection of GM-CSF.
Arm Title
Plain embolization
Arm Type
Active Comparator
Arm Description
Liver embolization with normal saline injected in place of GM-CSF
Intervention Type
Drug
Intervention Name(s)
GM-CSF
Other Intervention Name(s)
granulocyte-macrophage colony stimulating factor
Intervention Description
2,000 mcg injected into the liver every 4 weeks alternating between right or left lobe when tumors present throughout liver.
Intervention Type
Procedure
Intervention Name(s)
Embolization
Other Intervention Name(s)
embo
Intervention Description
A catheter will be introduced to one of the hepatic arteries by way of the femoral artery (groin) to allow injection of GM-CSF in combination with ethiodized oil and gelatin sponge providing a temporary blockage of the blood supply from the hepatic (liver) artery
Primary Outcome Measure Information:
Title
Response of Liver Metastases
Description
Complete response: Disappearance of all target and non-target liver lesions Partial response: >= 30% decrease in the sum of the longest diameters (LD) relative to baseline sum LD with at least stable non-target liver lesions Stable disease: Absence of change which would qualify as response or progression Progression: >= 20% increase in the sum LD in target liver lesions or unequivocal progression of non-target liver lesions in the treated lobe(s) or appearance of one or more new liver lesions >= 10mm in the treated lobe(s)
Time Frame
Every 8 weeks
Title
Overall Response Rate
Description
Clinical response in the liver metastases will be evaluated after every two embolizations using CT scans or MRI of the abdomen. The sum of the longest diameter (LD) of up to 6 target lesions will be used to determine response. Target indicator lesions will be identified and measured as baseline prior to the first embolization. The same target lesions will then be measured 3 to 4 weeks after every two treatments. The sum of the baseline LDs will be compared to the sum of the LDs after every two treatments.
Time Frame
Baseline then 3 to 4 weeks after every 2 treatments
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Measured from the start of the treatment to death of patients
Time Frame
Baseline to death
Title
Median Progression Free Survival
Description
Measured from the start of the treatment to confirmation of progression of disease by either imaging tests or physical examination. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of one or more new liver lesions >= 10mm in the treated lobe(s).
Time Frame
Baseline to time of progression
Title
Systemic Progression Free Survival
Description
Measured from the start of the treatment to confirmation of progression of disease by either imaging tests or physical examination. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of one or more new liver lesions >= 10mm in the treated lobe(s).
Time Frame
Baseline to time of progression

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Metastatic uveal melanoma in the liver with histological confirmation Ability/willingness to give informed consent ECOG performance status of 0 or 1 Adequate renal, liver and bone marrow function Exclusion Criteria: Solitary liver metastasis that is amenable to surgical removal Presence of symptomatic liver failure including ascites and hepatic encephalopathy Presence of extra-hepatic metastases Untreated brain metastases Uncontrolled hypertension or congestive heart failure or acute myocardial infarction within 6 months of entry Presence of any other medical complication that imply survival of less than six months Uncontrolled sever bleeding tendency or active GI bleeding Significant allergic reaction to contrast dye or GM-CSF Immunosuppressive treatments such as systemic steroids, radiation to pelvis or systemic chemotherapy within 4 weeks Previous embolization of the hepatic artery or intrahepatic arterial chemotherapy of liver metastasis Active hepatitis with serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) greater than 5 x normal HIV infection positive by ELISA Pregnancy or breast feeding women Biliary obstruction, biliary stent or prior biliary surgery except cholecystectomy Significant arteriovenous shunt identified on angiography of the hepatic artery Occlusion of main portal vein or inadequate collateral flow around an occluded portal vein
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Takami Sato, M.D., Ph.D.
Organizational Affiliation
Thomas Jefferson University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19317
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Halt Growth of Liver Tumors From Uveal Melanoma With Closure of Liver Artery Following Injection of GM-CSF

We'll reach out to this number within 24 hrs