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

Study Overview
=================
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).

Official Title
-----------------
Immuno-embolization of Hepatic Artery With Granulocyte-macrophage Colony Stimulating Factor (GM-CSF)

Conditions
-----------------
Uveal Melanoma, Liver Metastases

Intervention / Treatment
-----------------
* Drug: GM-CSF
* Procedure: Embolization


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immunoembolization<br>Liver embolization treatment with injection of GM-CSF. | Drug: GM-CSF<br>* 2,000 mcg injected into the liver every 4 weeks alternating between right or left lobe when tumors present throughout liver.<br>* Other names: granulocyte-macrophage colony stimulating factor;Procedure: Embolization<br>* 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<br>* Other names: embo;|
| Active Comparator: Plain embolization<br>Liver embolization with normal saline injected in place of GM-CSF | Procedure: Embolization<br>* 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<br>* Other names: embo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | Every 8 weeks | 
| 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. | Baseline then 3 to 4 weeks after every 2 treatments | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Measured from the start of the treatment to death of patients | Baseline to death | 
| 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). | Baseline to time of progression | 
| 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). | Baseline to time of progression |