[18F]FMISO PET/CT After Transcatheter Arterial Embolization in Imaging Tumors in Patients With Liver Cancer

• Sponsor: Sanjiv Sam Gambhir (Other)
• Overall Status: Completed
• CT.gov ID: NCT02695628
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 5
• Location: 1
• Arm: 1
• Actual Duration (Months): 25.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This clinical trial studies how well 18F-fluoromisonidazole ([18F]FMISO) positron emission tomography (PET)/computed tomography (CT) works after transcatheter arterial embolization in imaging tumors in patients with liver cancer. Transcatheter arterial embolization blocks blood flow to tumor cells by inserting tiny foreign particles into an artery near the tumor. [18F]FMISO is a type of radioimaging agent that binds to large molecules in tumor cells that have a low level of oxygen, and the radiation given off by [18F]FMISO is picked up by a PET scan and this may help researchers learn whether changes occur in the tumors after treatment, which can help decide how well the treatment worked earlier than is currently possible

Condition or Disease	Intervention/Treatment	Phase
Adult Liver Carcinoma; Liver Cirrhosis	Drug: 18F-Fluoromisonidazole; Procedure: Arterial Embolization; Diagnostic Test: Computed Tomography; Diagnostic Test: Positron Emission Tomography	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the variability of 18F FMISO uptake in hepatocellular carcinoma (HCC) tumors compared to normal liver after transcatheter arterial embolization by determining the difference in the mean of the maximum standardized uptake value (SUVmax) and tumor-to-liver ratio (TLR) of a region of normal liver and of up to 5 index tumors.

SECONDARY OBJECTIVES:

1. Determine if areas of tumor recurrence as determined by CT or magnetic resonance imaging (MRI) within a 6 month period after transcatheter arterial embolization show evidence of increased 18F FMISO labeling on the initial post treatment 18F FMISO PET/CT.

2. Determine the variability in SUVmax and TLR of untreated (non embolized) HCC lesions compared to normal liver by determining the difference in the mean of the SUVmax and TLR of normal liver and tumor.

3. Determine any toxicities related to [18F]FMISO use for PET/CT.

OUTLINE:

Patients undergo transcatheter arterial embolization. Patients also receive 18F-fluoromisonidazole intravenously (IV) and undergo PET/CT scans within 4 weeks prior to embolization treatment and in the 20 hours following completion of treatment.

After completion of treatment, patients are followed up at 2 and 3 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Assessment of Treatment-Induced Tissue Hypoxia After Transcatheter Arterial Embolization of Hepatocellular Carcinoma: A Feasibility Study With [18F]FMISO PET/CT
• Actual Study Start Date: Sep 13, 2016
• Actual Primary Completion Date: Apr 30, 2018
• Actual Study Completion Date: Oct 31, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Diagnostic (18F-fluoromisonidazole, PET/CT, embolization) Patients undergo transcatheter arterial embolization. Patients also receive 18F-fluoromisonidazole IV and undergo PET/CT scans 4 weeks prior to embolization treatment and in the 20 hours following completion of treatment.

Drug: 18F-Fluoromisonidazole; Undergo [18F] FMISO PET/CT; Other Names: 18F-MISO 18F-Misonidazole FMISO ; Procedure: Arterial Embolization; Undergo transcatheter arterial embolization; Other Names: TAE Transarterial Embolization ; Diagnostic Test: Computed Tomography; Undergo [18F] FMISO PET/CT; Other Names: CAT CAT Scan Computerized Axial Tomography Computerized Tomography CT CT SCAN tomography ; Diagnostic Test: Positron Emission Tomography; Undergo [18F] FMISO PET/CT; Other Names: Medical Imaging, Positron Emission Tomography PET PET SCAN Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging

Outcome Measures

Primary Outcome Measures

1. Post-treatment Maximum Standardized Uptake Value (SUVmax) in Tumor and Normal Tissue [24 hours]

   All participants undergo transcatheter arterial embolization (TACE) and 18F-fluoromisonidazole (18F-FMISO) positron emission tomography (PET)/computed tomography (CT) scans were conducted. Maximum standardized uptake value (SUVmax) were determined at the tumor lesion and in normal tissue, represented by liver. The variability of 18F-FMISO uptake in hepatocellular carcinoma (HCC) tumors post-TACE was assessed as the ratio of the SUVmax as observed in the tumor vs liver (tumor-to-liver ratio, TLR). The outcome is reported as the mean TLR, with standard deviation.

Secondary Outcome Measures

1. Maximum Standardized Uptake Value (SUVmax) at Lesion Sites With and Without Tumor Recurrence [Up to 6 months]

   Follow-up 18F-fluoromisonidazole (18F-FMISO) positron emission tomography (PET)/computed tomography (CT) scans were to be conducted within 6 months or at the time of tumor recurrence. Maximum standardized uptake value (SUVmax) were determined at the tumor lesion and in normal tissue, represented by liver. The variability of 18F-FMISO uptake at the hepatocellular carcinoma (HCC) tumor lesion site post-TACE was assessed as the mean difference in the ratio of the SUVmax as observed in the tumor vs liver (tumor-to-liver ratio, TLR), between lesions that recurred, and those that did not. The outcome is reported as the mean TLR, with standard deviation.

2. Adverse Events Related to 18F-fluoromisonidazole (18F-FMISO) [18 hours]

   Toxicity to 18F-fluoromisonidazole (18F-FMISO) was assessed by the number of adverse events that occurred within 18 hours of administration (about 10 half-lives), that were also unanticipated and related to 18F-FMISO. The outcome is reported as the number of adverse events that were unanticipated and related to 18F-FMISO, a number without dispersion.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

• Histopathologic or imaging and clinical features of tumor(s) diagnostic for hepatocellular carcinoma with at least one tumor >= 1.5 cm; imaging features diagnostic for hepatocellular carcinoma will be defined as Liver Imaging Reporting and Data System (LIRADS) 4 or greater

• Total bilirubin < 3.0

• Child Pugh A or B

• Tumor amenable to transcatheter arterial embolization

• Able to provide informed consent

Exclusion Criteria:

• Uncontrolled large ascites

• Main or segmental portal vein thrombosis

• Locoregional treatment of hepatocellular carcinoma within the prior 3 months or chemotherapy within the previous 3 months

• Inability or contraindication to undergo transcatheter arterial embolization

• Inability to lay flat for at least 2 consecutive hours

• Severe acute illness

• Uncontrolled chronic illness such as hypertension, diabetes, or heart failure

• Contraindication to CT or MRI contrast

• Pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Palo Alto Healthcare System	Palo Alto	California	United States	94304

Sponsors and Collaborators

• Sanjiv Sam Gambhir
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Rajesh Shah, Stanford Cancer Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 28, 2015
• Informed Consent Form - Oct 10, 2017

More Information

Publications

None provided.

• Responsible Party: Sanjiv Sam Gambhir, Principal Investigator, Stanford University
• ClinicalTrials.gov Identifier: NCT02695628
• Other Study ID Numbers: IRB-29768; NCI-2016-00041; HEP0055; P30CA124435
• First Posted: Mar 1, 2016
• Last Update Posted: May 22, 2019
• Last Verified: May 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Liver Cirrhosis; Misonidazole

Study Results

Participant Flow

Arm/Group Title	Diagnostic (18F-fluoromisonidazole, PET/CT, Embolization)
Arm/Group Description	Patients undergo transcatheter arterial embolization. Patients also receive 18F-fluoromisonidazole IV and undergo PET/CT scans 4 weeks prior to embolization treatment and in the 20 hours following completion of treatment. 18F-Fluoromisonidazole: Undergo [18F] FMISO PET/CT Arterial Embolization: Undergo transcatheter arterial embolization Computed Tomography: Undergo [18F] FMISO PET/CT Positron Emission Tomography: Undergo [18F] FMISO PET/CT
Period Title: Overall Study
STARTED	5
COMPLETED	4
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Diagnostic (18F-fluoromisonidazole, PET/CT, Embolization)
Arm/Group Description	Patients undergo transcatheter arterial embolization. Patients also receive 18F-fluoromisonidazole IV and undergo PET/CT scans 4 weeks prior to embolization treatment and in the 20 hours following completion of treatment. 18F-Fluoromisonidazole: Undergo [18F] FMISO PET/CT Arterial Embolization: Undergo transcatheter arterial embolization Computed Tomography: Undergo [18F] FMISO PET/CT Positron Emission Tomography: Undergo [18F] FMISO PET/CT
Overall Participants	5
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 20%
>=65 years	4 80%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	66.6 (5.59)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	5 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 20%
Not Hispanic or Latino	4 80%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 20%
White	4 80%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%
Maximum Standardized Uptake Value (SUVmax) in Tumor vs Normal Tissue (Ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Ratio]	0.71 (0.22)

Outcome Measures

1. Primary Outcome

Title	Post-treatment Maximum Standardized Uptake Value (SUVmax) in Tumor and Normal Tissue
Description	All participants undergo transcatheter arterial embolization (TACE) and 18F-fluoromisonidazole (18F-FMISO) positron emission tomography (PET)/computed tomography (CT) scans were conducted. Maximum standardized uptake value (SUVmax) were determined at the tumor lesion and in normal tissue, represented by liver. The variability of 18F-FMISO uptake in hepatocellular carcinoma (HCC) tumors post-TACE was assessed as the ratio of the SUVmax as observed in the tumor vs liver (tumor-to-liver ratio, TLR). The outcome is reported as the mean TLR, with standard deviation.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Due to withdrawal, not all participants completed for this outcome.

Arm/Group Title	Diagnostic (18F-fluoromisonidazole, PET/CT, Embolization)
Arm/Group Description	Patients undergo transcatheter arterial embolization. Patients also receive 18F-fluoromisonidazole IV and undergo PET/CT scans 4 weeks prior to embolization treatment and in the 20 hours following completion of treatment. 18F-Fluoromisonidazole: Undergo [18F] FMISO PET/CT Arterial Embolization: Undergo transcatheter arterial embolization Computed Tomography: Undergo [18F] FMISO PET/CT Positron Emission Tomography: Undergo [18F] FMISO PET/CT
Measure Participants	4
Mean (Standard Deviation) [Ratio]	0.76 (0.14)

2. Secondary Outcome

Title	Maximum Standardized Uptake Value (SUVmax) at Lesion Sites With and Without Tumor Recurrence
Description	Follow-up 18F-fluoromisonidazole (18F-FMISO) positron emission tomography (PET)/computed tomography (CT) scans were to be conducted within 6 months or at the time of tumor recurrence. Maximum standardized uptake value (SUVmax) were determined at the tumor lesion and in normal tissue, represented by liver. The variability of 18F-FMISO uptake at the hepatocellular carcinoma (HCC) tumor lesion site post-TACE was assessed as the mean difference in the ratio of the SUVmax as observed in the tumor vs liver (tumor-to-liver ratio, TLR), between lesions that recurred, and those that did not. The outcome is reported as the mean TLR, with standard deviation.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

Follow-up 18F-fluoromisonidazole (18F-FMISO) positron emission tomography (PET) scans at the time of tumor recurrence were not conducted.

Arm/Group Title	Diagnostic (18F-fluoromisonidazole, PET/CT, Embolization)
Arm/Group Description	Patients undergo transcatheter arterial embolization. Patients also receive 18F-fluoromisonidazole IV and undergo PET/CT scans 4 weeks prior to embolization treatment and in the 20 hours following completion of treatment. 18F-Fluoromisonidazole: Undergo [18F] FMISO PET/CT Arterial Embolization: Undergo transcatheter arterial embolization Computed Tomography: Undergo [18F] FMISO PET/CT Positron Emission Tomography: Undergo [18F] FMISO PET/CT
Measure Participants	0

3. Secondary Outcome

Title	Adverse Events Related to 18F-fluoromisonidazole (18F-FMISO)
Description	Toxicity to 18F-fluoromisonidazole (18F-FMISO) was assessed by the number of adverse events that occurred within 18 hours of administration (about 10 half-lives), that were also unanticipated and related to 18F-FMISO. The outcome is reported as the number of adverse events that were unanticipated and related to 18F-FMISO, a number without dispersion.
Time Frame	18 hours

Outcome Measure Data

Analysis Population Description

All participants are included for this outcome.

Arm/Group Title	Diagnostic (18F-fluoromisonidazole, PET/CT, Embolization)
Arm/Group Description	Patients undergo transcatheter arterial embolization. Patients also receive 18F-fluoromisonidazole IV and undergo PET/CT scans 4 weeks prior to embolization treatment and in the 20 hours following completion of treatment. 18F-Fluoromisonidazole: Undergo [18F] FMISO PET/CT Arterial Embolization: Undergo transcatheter arterial embolization Computed Tomography: Undergo [18F] FMISO PET/CT Positron Emission Tomography: Undergo [18F] FMISO PET/CT
Measure Participants	5
Number [Number of adverse events]	0

Adverse Events

Time Frame	6 months
Arm/Group Title	Diagnostic (18F-fluoromisonidazole, PET/CT, Embolization)
Arm/Group Description	Patients undergo transcatheter arterial embolization. Patients also receive 18F-fluoromisonidazole IV and undergo PET/CT scans 4 weeks prior to embolization treatment and in the 20 hours following completion of treatment. 18F-Fluoromisonidazole: Undergo [18F] FMISO PET/CT Arterial Embolization: Undergo transcatheter arterial embolization Computed Tomography: Undergo [18F] FMISO PET/CT Positron Emission Tomography: Undergo [18F] FMISO PET/CT
All Cause Mortality
	Diagnostic (18F-fluoromisonidazole, PET/CT, Embolization)
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Serious Adverse Events
	Diagnostic (18F-fluoromisonidazole, PET/CT, Embolization)
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Other (Not Including Serious) Adverse Events
	Diagnostic (18F-fluoromisonidazole, PET/CT, Embolization)
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Gastrointestinal disorders
Diarrhea	1/5 (20%)	1
Nausea	2/5 (40%)	2
General disorders
Fatigue	4/5 (80%)	4
Edema limbs	1/5 (20%)	1
Hepatobiliary disorders
Hepatic pain	2/5 (40%)	3
Hepatobiliary disorders -Other, increased liver functions	2/5 (40%)	2
Infections and infestations
Infections and infestations -Other, Cellulitis	1/5 (20%)	1

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.