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

Phase 2

Completed

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).

Recruitment & Eligibility

Inclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
Immunoembolization	Embolization	Liver embolization treatment with injection of GM-CSF.
Plain embolization	Embolization	Liver embolization with normal saline injected in place of GM-CSF
Immunoembolization	GM-CSF	Liver embolization treatment with injection of GM-CSF.

Primary Outcome Measures

Name	Time	Method
Response of Liver Metastases	Every 8 weeks	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	Baseline then 3 to 4 weeks after every 2 treatments	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

Name	Time	Method
Overall Survival	Baseline to death	Measured from the start of the treatment to death of patients
Median Progression Free Survival	Baseline to time of progression	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	Baseline to time of progression	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).

Locations (1): Thomas Jefferson University
🇺🇸
Philadelphia, Pennsylvania, United States