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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT00661622
First received: April 16, 2008
Last updated: May 15, 2015
Last verified: May 2015
  Purpose

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.

Condition Intervention Phase
Uveal Melanoma
Liver Metastases
Drug: GM-CSF
Procedure: Embolization
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Immuno-embolization of Hepatic Artery With Granulocyte-macrophage Colony Stimulating Factor (GM-CSF)

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • Response of Liver Metastases [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline then 3 to 4 weeks after every 2 treatments ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to death ] [ Designated as safety issue: No ]
    Measured from the start of the treatment to death of patients

  • Median Progression Free Survival [ Time Frame: Baseline to time of progression ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline to time of progression ] [ Designated as safety issue: No ]

    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).



Enrollment: 53
Study Start Date: October 2004
Study Completion Date: June 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Immunoembolization
Liver embolization treatment with injection of GM-CSF.
Drug: GM-CSF
2,000 mcg injected into the liver every 4 weeks alternating between right or left lobe when tumors present throughout liver.
Other Name: granulocyte-macrophage colony stimulating factor
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
Other Name: embo
Active Comparator: Plain embolization
Liver embolization with normal saline injected in place of GM-CSF
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
Other Name: embo

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00661622

Locations
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19317
Sponsors and Collaborators
Thomas Jefferson University
Investigators
Principal Investigator: Takami Sato, M.D., Ph.D. Thomas Jefferson University
  More Information

No publications provided

Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT00661622     History of Changes
Other Study ID Numbers: 04F.445, R21CA103250
Study First Received: April 16, 2008
Results First Received: March 24, 2015
Last Updated: May 15, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Uveal Neoplasms
Eye Diseases
Eye Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Uveal Diseases

ClinicalTrials.gov processed this record on September 02, 2015