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

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00661622
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 53
• Location: 1
• Arms: 2
• Duration (Months): 92
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Uveal Melanoma; Liver Metastases	Drug: GM-CSF; Procedure: Embolization	Phase 2

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Immuno-embolization of Hepatic Artery With Granulocyte-macrophage Colony Stimulating Factor (GM-CSF)
• Study Start Date: Oct 1, 2004
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: 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 Names: embo

Outcome Measures

Primary Outcome Measures

1. 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)

2. 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

1. Overall Survival [Baseline to death]

   Measured from the start of the treatment to death of patients

2. 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).

3. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19317

Sponsors and Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Takami Sato, M.D., Ph.D., Thomas Jefferson University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Cancer Center at Thomas Jefferson University
• ClinicalTrials.gov Identifier: NCT00661622
• Other Study ID Numbers: 04F.445; R21CA103250
• First Posted: Apr 18, 2008
• Last Update Posted: Nov 29, 2016
• Last Verified: Oct 1, 2016

• Additional relevant MeSH terms: Melanoma; Molgramostim; Sargramostim

Study Results

Participant Flow

Arm/Group Title	Immunoembolization	Plain Embolization
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	26	27
COMPLETED	25	27
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Immunoembolization	Plain Embolization	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	25	27	52
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56	62	58
Sex: Female, Male (Count of Participants)
Female	15 60%	12 44.4%	27 51.9%
Male	10 40%	15 55.6%	25 48.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	25 100%	27 100%	52 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	25 100%	27 100%	52 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	25 100%	27 100%	52 100%

Outcome Measures

1. Primary Outcome

Title	Response of Liver Metastases
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Immunoembolization	Plain Embolization
Arm/Group Description	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	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 GM-CSF in combination with ethiodized oil and gelatin sponge providing a temporary blockage of the blood supply from the hepatic (liver) artery
Measure Participants	26	27
Complete response (CR)	0 0%	0 0%
Partial response (PR)	5 20%	3 11.1%
Stable disease (SD)	12 48%	19 70.4%
Progression (PD)	8 32%	5 18.5%

2. Primary Outcome

Title	Overall Response Rate
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Immunoembolization	Plain Embolization
Arm/Group Description	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	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
Measure Participants	26	27
Number (90% Confidence Interval) [percentage of participants]	21.2 84.8%	16.7 61.9%

3. Secondary Outcome

Title	Overall Survival
Description	Measured from the start of the treatment to death of patients
Time Frame	Baseline to death

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Immunoembolization	Plain Embolization
Arm/Group Description	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	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
Measure Participants	26	27
Median (95% Confidence Interval) [months]	21.5	17.2

4. Secondary Outcome

Title	Median Progression Free Survival
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Immunoembolization	Plain Embolization
Arm/Group Description	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	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
Measure Participants	26	27
Median (95% Confidence Interval) [months]	3.9	5.9

5. Secondary Outcome

Title	Systemic Progression Free Survival
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Immunoembolization	Plain Embolization
Arm/Group Description	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	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
Measure Participants	26	27
Median (95% Confidence Interval) [months]	10.4	7.1

Adverse Events

Arm/Group Title	Immunoembolization		Plain Embolization
Arm/Group Description	Liver embolization treatment with injection of GM-CSF.		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
All Cause Mortality
	Immunoembolization		Plain Embolization
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Immunoembolization		Plain Embolization
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/26 (11.5%)		5/27 (18.5%)
Blood and lymphatic system disorders
Aneurysms	1/26 (3.8%)	1	0/27 (0%)	0
Gastrointestinal disorders
Diarrhea	0/26 (0%)	0	1/27 (3.7%)	1
General disorders
Abdominal pain	0/26 (0%)	0	1/27 (3.7%)	1
Death	0/26 (0%)	0	1/27 (3.7%)	1
Fever	0/26 (0%)	0	1/27 (3.7%)	1
Hepatobiliary disorders
Elevated liver enzymes	2/26 (7.7%)	2	1/27 (3.7%)	1
Liver pain	0/26 (0%)	0	1/27 (3.7%)	1
Other (Not Including Serious) Adverse Events
	Immunoembolization		Plain Embolization
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/26 (100%)		23/27 (85.2%)
Blood and lymphatic system disorders
Decreased granulocytes	2/26 (7.7%)	2	0/27 (0%)	0
Decreased hemoglobin	16/26 (61.5%)	96	17/27 (63%)	147
Decreased WBC	2/26 (7.7%)	6	4/27 (14.8%)	4
Fluid overload	0/26 (0%)	0	1/27 (3.7%)	1
Hyperglycemia	1/26 (3.8%)	1	0/27 (0%)	0
Hypertension	1/26 (3.8%)	2	0/27 (0%)	0
Hypoalbuminemia	1/26 (3.8%)	4	0/27 (0%)	0
Hypotension	3/26 (11.5%)	6	2/27 (7.4%)	4
Increased bilirubin	2/26 (7.7%)	3	2/27 (7.4%)	2
Increased alkaline phosphatase	9/26 (34.6%)	31	9/27 (33.3%)	36
Increased creatinine	2/26 (7.7%)	8	1/27 (3.7%)	1
Increased SGOT	22/26 (84.6%)	97	22/27 (81.5%)	114
Increased SGPT	22/26 (84.6%)	109	22/27 (81.5%)	117
Leukopenia	8/26 (30.8%)	32	10/27 (37%)	26
Lymphpenia	1/26 (3.8%)	8	2/27 (7.4%)	2
Neutropenia	1/26 (3.8%)	2	0/27 (0%)	0
Thrombocytopenia	6/26 (23.1%)	44	5/27 (18.5%)	13
Cardiac disorders
Bradycardia	1/26 (3.8%)	1	1/27 (3.7%)	1
Heart palpitations	1/26 (3.8%)	1	0/27 (0%)	0
Sinus tachycardia	0/26 (0%)	0	1/27 (3.7%)	1
Ear and labyrinth disorders
Hearing loss	0/26 (0%)	0	1/27 (3.7%)	2
Eye disorders
Blurred vision	1/26 (3.8%)	1	1/27 (3.7%)	1
Decreased visual acuity	0/26 (0%)	0	2/27 (7.4%)	2
Gastrointestinal disorders
Belching	1/26 (3.8%)	1	0/27 (0%)	0
Bloating	1/26 (3.8%)	2	0/27 (0%)	0
Constipation	5/26 (19.2%)	8	5/27 (18.5%)	10
Diarrhea	3/26 (11.5%)	10	5/27 (18.5%)	8
Flatulence	2/26 (7.7%)	3	1/27 (3.7%)	1
Gastroesophageal reflux disease	0/26 (0%)	0	4/27 (14.8%)	10
Dyspepsia	0/26 (0%)	0	1/27 (3.7%)	1
Vomiting	7/26 (26.9%)	22	6/27 (22.2%)	9
General disorders
Agitation	1/26 (3.8%)	1	1/27 (3.7%)	1
Anorexia	4/26 (15.4%)	6	5/27 (18.5%)	13
Back pain	0/26 (0%)	0	1/27 (3.7%)	1
Bleeding	1/26 (3.8%)	2	3/27 (11.1%)	3
Bleeding at procedure site	1/26 (3.8%)	1	1/27 (3.7%)	1
Burning upper quadrant pain	0/26 (0%)	0	1/27 (3.7%)	1
Chills/rigors	4/26 (15.4%)	6	3/27 (11.1%)	3
Delayed healing of insertion site	0/26 (0%)	0	1/27 (3.7%)	2
Diaphoresis	1/26 (3.8%)	1	0/27 (0%)	0
Disequilibrium	1/26 (3.8%)	1	0/27 (0%)	0
Dizziness	3/26 (11.5%)	3	5/27 (18.5%)	19
Drug allergy	0/26 (0%)	0	1/27 (3.7%)	1
Dry mouth	0/26 (0%)	0	1/27 (3.7%)	1
Dysgeusia	1/26 (3.8%)	2	2/27 (7.4%)	3
Epigastric pain	0/26 (0%)	0	1/27 (3.7%)	2
Fatigue	11/26 (42.3%)	26	9/27 (33.3%)	26
Fever	9/26 (34.6%)	15	8/27 (29.6%)	14
Flu	1/26 (3.8%)	1	2/27 (7.4%)	2
Headache	1/26 (3.8%)	1	3/27 (11.1%)	6
Hoarseness	1/26 (3.8%)	2	0/27 (0%)	0
Hot flashes	0/26 (0%)	0	1/27 (3.7%)	3
Insomnia	1/26 (3.8%)	2	4/27 (14.8%)	4
Irritation	1/26 (3.8%)	1	0/27 (0%)	0
Joint pain	0/26 (0%)	0	2/27 (7.4%)	2
Lethargy	1/26 (3.8%)	1	0/27 (0%)	0
Muscle cramp	0/26 (0%)	0	1/27 (3.7%)	1
Muscle pain	0/26 (0%)	0	1/27 (3.7%)	1
Nausea	17/26 (65.4%)	63	13/27 (48.1%)	27
Night sweats	2/26 (7.7%)	2	1/27 (3.7%)	2
Nose bleed	0/26 (0%)	0	2/27 (7.4%)	3
Orthostatic hypotension	0/26 (0%)	0	1/27 (3.7%)	1
Pain	21/26 (80.8%)	84	22/27 (81.5%)	98
Sensitivity to heat	1/26 (3.8%)	1	1/27 (3.7%)	2
Sinus allergies	1/26 (3.8%)	1	0/27 (0%)	0
Sinus pain	1/26 (3.8%)	2	0/27 (0%)	0
Slurred speech	1/26 (3.8%)	1	0/27 (0%)	0
Sprained ankle	0/26 (0%)	0	1/27 (3.7%)	1
Stiff neck	0/26 (0%)	0	1/27 (3.7%)	1
Sweating	0/26 (0%)	0	2/27 (7.4%)	4
Swollen knee	0/26 (0%)	0	1/27 (3.7%)	1
Tachycardia	1/26 (3.8%)	1	0/27 (0%)	0
Upper respiratory infection	0/26 (0%)	0	1/27 (3.7%)	1
Weakness	0/26 (0%)	0	4/27 (14.8%)	5
Weight loss	0/26 (0%)	0	2/27 (7.4%)	2
Infections and infestations
Fungal nail infection	0/26 (0%)	0	1/27 (3.7%)	1
Skin infection	0/26 (0%)	0	1/27 (3.7%)	1
Musculoskeletal and connective tissue disorders
Athritis	0/26 (0%)	0	2/27 (7.4%)	3
Nervous system disorders
Neuropathy	0/26 (0%)	0	1/27 (3.7%)	1
Psychiatric disorders
Anxiety	2/26 (7.7%)	2	3/27 (11.1%)	5
Depression	0/26 (0%)	0	1/27 (3.7%)	1
Personality change	0/26 (0%)	0	1/27 (3.7%)	1
Respiratory, thoracic and mediastinal disorders
Bronchitis	0/26 (0%)	0	1/27 (3.7%)	1
Cold	1/26 (3.8%)	1	2/27 (7.4%)	5
Cough	1/26 (3.8%)	1	1/27 (3.7%)	1
Dyspnea	3/26 (11.5%)	7	2/27 (7.4%)	2
Pneumonitis	1/26 (3.8%)	1	0/27 (0%)	0
Skin and subcutaneous tissue disorders
Angioedema	0/26 (0%)	0	1/27 (3.7%)	1
Bruising	2/26 (7.7%)	3	4/27 (14.8%)	4
Bruising at cath site	1/26 (3.8%)	1	0/27 (0%)	0
Cellulitis	0/26 (0%)	0	1/27 (3.7%)	1
Edema	0/26 (0%)	0	1/27 (3.7%)	1
Hematoma	0/26 (0%)	0	2/27 (7.4%)	2
Pruritis	0/26 (0%)	0	1/27 (3.7%)	1
Rash	4/26 (15.4%)	11	3/27 (11.1%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.