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

Liver Metastases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00661622
• Other study ID #: 04F.445
• Secondary ID: R21CA103250
• Status: Completed
• Phase: Phase 2
• First received: April 16, 2008
• Last updated: January 8, 2016
• Start date: October 2004
• Est. completion date: June 2012

Study information

• Verified date: January 2016
• Source: Thomas Jefferson University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: June 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Metastases
• Melanoma
• Uveal Melanoma
• Uveal Neoplasms

Intervention

Drug:
• GM-CSF
2,000 mcg injected into the liver every 4 weeks alternating between right or left lobe when tumors present throughout liver.

Procedure:
• Embolization
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

Locations

Country	Name	City	State
United States	Thomas Jefferson University	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Thomas Jefferson University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	Overall Survival	Measured from the start of the treatment to death of patients	Baseline to death	No
Secondary	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	No
Secondary	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	No