Liver Metastases, Uveal Melanoma
Conditions
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).
Interventions
DRUGGM-CSF
2,000 mcg injected into the liver every 4 weeks alternating between right or left lobe when tumors present throughout liver.
PROCEDUREEmbolization
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
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Cancer Center at Thomas Jefferson University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Immunoembolization Liver embolization treatment with injection of GM-CSF.
GM-CSF: 2,000 mcg injected into the liver every 4 weeks alternating between right or left lobe when tumors present throughout liver.
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 | 25 |
| Plain Embolization Liver embolization with normal saline injected in place of GM-CSF
Embolization: A catheter will be introduced to one of the hepatic arteries by way of the femoral artery (groin) to allow injection of normal saline in combination with ethiodized oil and gelatin sponge providing a temporary blockage of the blood supply from the hepatic (liver) artery | 27 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Immunoembolization | Plain Embolization |
|---|---|---|---|
| Age, Continuous | 58 years | 56 years | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants | 25 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 52 Participants | 25 Participants | 27 Participants |
| Region of Enrollment United States | 52 participants | 25 participants | 27 participants |
| Sex: Female, Male Female | 27 Participants | 15 Participants | 12 Participants |
| Sex: Female, Male Male | 25 Participants | 10 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 26 / 26 | 23 / 27 |
| serious Total, serious adverse events | 3 / 26 | 5 / 27 |
Outcome results
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.
Time frame: Baseline then 3 to 4 weeks after every 2 treatments
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immunoembolization | Overall Response Rate | 21.2 percentage of participants |
| Plain Embolization | Overall Response Rate | 16.7 percentage of participants |
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)
Time frame: Every 8 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Immunoembolization | Response of Liver Metastases | Complete response (CR) | 0 participants |
| Immunoembolization | Response of Liver Metastases | Partial response (PR) | 5 participants |
| Immunoembolization | Response of Liver Metastases | Stable disease (SD) | 12 participants |
| Immunoembolization | Response of Liver Metastases | Progression (PD) | 8 participants |
| Plain Embolization | Response of Liver Metastases | Progression (PD) | 5 participants |
| Plain Embolization | Response of Liver Metastases | Complete response (CR) | 0 participants |
| Plain Embolization | Response of Liver Metastases | Stable disease (SD) | 19 participants |
| Plain Embolization | Response of Liver Metastases | Partial response (PR) | 3 participants |
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).
Time frame: Baseline to time of progression
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Immunoembolization | Median Progression Free Survival | 3.9 months |
| Plain Embolization | Median Progression Free Survival | 5.9 months |
Secondary
Overall Survival
Measured from the start of the treatment to death of patients
Time frame: Baseline to death
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Immunoembolization | Overall Survival | 21.5 months |
| Plain Embolization | Overall Survival | 17.2 months |
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).
Time frame: Baseline to time of progression
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Immunoembolization | Systemic Progression Free Survival | 10.4 months |
| Plain Embolization | Systemic Progression Free Survival | 7.1 months |