PET/CT Evaluation of Primary and Metastatic Brain Tumors With a Novel Radioiodinated Phospholipid Ether Analogue I-NM404

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Completed
• CT.gov ID: NCT01540513
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arm: 1
• Duration (Months): 31
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate diagnostic imaging techniques using 124I-NM404 PET/CT in human brain tumors. This goal will be accomplished by quantifying tumor uptake and determining the optimal PET/CT protocol, comparing PET tumor uptake to MRI, and calculating tumor dosimetry. The long-term goals of this research are to improve the diagnosis and treatment of malignant brain tumors by using radioiodinated NM404

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Multiforme; Brain Metastases	Drug: NM404; Drug: NM404	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: PET/CT Evaluation of Primary and Metastatic Brain Tumors With a Novel Radioiodinated Phospholipid Ether Analogue I-NM404
• Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: I124-NM404 brain metastases or GBM imaging injection of I-124NM404 for imaging	Drug: NM404; injection of 5.0mCi I-124 NM404 Arms: I124-NM404 brain metastases or GBM imaging Other Names: PET imaging with I-124 NM404; Drug: NM404; injection of an experimental imaging agent, 5mCi I-124NM404

Outcome Measures

Primary Outcome Measures

1. Tumor to Background Ratios (TBR) Post-imaging for All Lesions With PET Uptake [24- and 48 hours post injection]

   TBR is calculated by using tumor/lesion SUVmax and dividing by contralateral normal brain background SUVmean value. Imaging performed at 24- and 48 hours post injection.

2. Tumor to Background Ratios (TBR) Post-imaging for Confirmed Malignant Tumors [24- and 48 hours post injection]

   TBR is calculated by using tumor/lesion SUVmax and dividing by contralateral normal brain background SUVmean value. Imaging performed at 24-, and 48 hours post injection.

3. Tumor to Blood Pool Ratios Post-imaging for All Lesions With PET Uptake [24- and 48 hours post injection]

   Tumor to blood pool ratio (tumor SUVmax to superior sinus SUVmean) was calculated at each time point. Tumor to blood pool is calculated by using tumor/lesion SUVmax and dividing by blood pool SUVmean from placing a region of interest in the posterior sagittal sinus near the confluence of sinuses. Imaging performed at 24- and 48 hours post injection.

4. Tumor to Blood Pool Ratios Post-imaging for Confirmed Malignant Tumors [24- and 48 hours post injection]

   Tumor to blood pool ratio (tumor SUVmax to superior sinus SUVmean) was calculated at each time point. Tumor to blood pool is calculated by using tumor/lesion SUVmax and dividing by blood pool SUVmean from placing a region of interest in the posterior sagittal sinus near the confluence of sinuses. Imaging performed at 24-, and 48 hours post injection.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants will have a contrast enhanced brain MRI which documents evidence of primary or metastatic brain tumor or suspected tumor recurrence after therapy

• Tumor size at least 1.5 cm in greatest axial dimension on MRI. MRI must be obtained within 2 months of study inclusion

• Adult patients 18 or older

• Female patients must not be pregnant or breast feeding and both women of childbearing potential, and men, must use appropriate means of contraception and must be maintained for at least 45 days after injection of 124I-NM404 Participants must not attempt to become pregnant during this time

• Platelet count must be ≥ 160,000/µl, Hematocrit must be ≥ 22%, Leukocyte count must be ≥ 3,000/µL, Creatinine must be ≤ 2.5 mg/dL, ALT must be ≤ 130 U/L, AST must be ≤ 100 U/L, and urine or serum pregnancy test must be negative for pregnancy

• Patient provides informed consent

• Karnofsky score ≥ 60

• For previously treated brain tumors, targeted brain therapy (radiation or drug) must have concluded ≥2 months prior to injection of 124I-NM404

Exclusion Criteria:

• Life expectancy of < 3 months

• Allergy to potassium iodide (SSKI or Thyroshield)

• Unwilling or unable to complete 3 separate PET/CT imaging sessions of 90 minutes each over 3 days

• Pregnancy or breast-feeding during time of study and/or anticipated breast feeding at any time for 45 days after injection of 124I-NM404.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• University of Wisconsin, Madison

Investigators

• Principal Investigator: Lance Hall, MD, University of Wisconsin, Madison

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Alkylphospohocholine Analogs for Broad-Spectrum Cancer Imaging and Therapy
• Impact of PET and MRI threshold-based tumor volume segmentation on patient-specific
• PET/CT imaging of the diapeutic alkylphosphocholine analog 124I-CLR1404 in high and low-grade brain tumors
• University of Wisconsin Carbone Cancer Center

Publications

None provided.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT01540513
• Other Study ID Numbers: RO11360; 2011-0830; NCI-2012-02080; A539300; SMPH\RADIOLOGY\RADIOLOGY
• First Posted: Feb 28, 2012
• Last Update Posted: Dec 2, 2019
• Last Verified: Feb 1, 2018

• Additional relevant MeSH terms: Glioblastoma; Brain Neoplasms

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from March 2012 to September 2014 at the University of Wisconsin Hospital and Clinics.

Arm/Group Title	I124-NM404 Brain Metastases or GBM Imaging
Arm/Group Description	Participants injected with 185 MBq ± of 124I-CLR1404 intravenously over a period of 1 to 2 minutes, followed by a flush of 10 mL of normal saline. Subjects returned for PET/CT imaging at 6-, 24-, and 48-hours post-injection. Participants received 3 drops of potassium iodide by mouth (1 gm/ml) 1 to 24 hours prior to injection of 124I-CLR1404 and continued additional daily doses prior to each PET/CT scan for 3 consecutive days.
Period Title: Overall Study
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	I124-NM404 Brain Metastases or GBM Imaging
Arm/Group Description	Participants injected with 185 MBq ± of 124I-CLR1404 intravenously over a period of 1 to 2 minutes, followed by a flush of 10 mL of normal saline. Subjects returned for PET/CT imaging at 6-, 24-, and 48-hours post-injection. Participants received 3 drops of potassium iodide by mouth (1 gm/ml) 1 to 24 hours prior to injection of 124I-CLR1404 and continued additional daily doses prior to each PET/CT scan for 3 consecutive days.
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 91.7%
>=65 years	1 8.3%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	43.9
Sex: Female, Male (Count of Participants)
Female	4 33.3%
Male	8 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	12 100%
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	0 0%
White	12 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	12 100%

Outcome Measures

1. Primary Outcome

Title	Tumor to Background Ratios (TBR) Post-imaging for All Lesions With PET Uptake
Description	TBR is calculated by using tumor/lesion SUVmax and dividing by contralateral normal brain background SUVmean value. Imaging performed at 24- and 48 hours post injection.
Time Frame	24- and 48 hours post injection

Outcome Measure Data

Analysis Population Description

Of 12 subjects, only 8 had evaluable data.

Arm/Group Title	I124-NM404 Brain Metastases or GBM Imaging
Arm/Group Description	Participants injected with 185 MBq ± of 124I-CLR1404 intravenously over a period of 1 to 2 minutes, followed by a flush of 10 mL of normal saline. Subjects returned for PET/CT imaging at 6-, 24-, and 48-hours post-injection. Participants received 3 drops of potassium iodide by mouth (1 gm/ml) 1 to 24 hours prior to injection of 124I-CLR1404 and continued additional daily doses prior to each PET/CT scan for 3 consecutive days.
Measure Participants	8
24 hours	8.25 (4.16)
48 hours	8.75 (3.60)

2. Primary Outcome

Title	Tumor to Background Ratios (TBR) Post-imaging for Confirmed Malignant Tumors
Description	TBR is calculated by using tumor/lesion SUVmax and dividing by contralateral normal brain background SUVmean value. Imaging performed at 24-, and 48 hours post injection.
Time Frame	24- and 48 hours post injection

Outcome Measure Data

Analysis Population Description

Of 12 participants, 8 had evaluable TBR data.

Arm/Group Title	I124-NM404 Brain Metastases or GBM Imaging
Arm/Group Description	Participants injected with 185 MBq ± of 124I-CLR1404 intravenously over a period of 1 to 2 minutes, followed by a flush of 10 mL of normal saline. Subjects returned for PET/CT imaging at 6-, 24-, and 48-hours post-injection. Participants received 3 drops of potassium iodide by mouth (1 gm/ml) 1 to 24 hours prior to injection of 124I-CLR1404 and continued additional daily doses prior to each PET/CT scan for 3 consecutive days.
Measure Participants	8
24 hours	9.32 (4.33)
48 hours	10.04 (3.15)

3. Primary Outcome

Title	Tumor to Blood Pool Ratios Post-imaging for All Lesions With PET Uptake
Description	Tumor to blood pool ratio (tumor SUVmax to superior sinus SUVmean) was calculated at each time point. Tumor to blood pool is calculated by using tumor/lesion SUVmax and dividing by blood pool SUVmean from placing a region of interest in the posterior sagittal sinus near the confluence of sinuses. Imaging performed at 24- and 48 hours post injection.
Time Frame	24- and 48 hours post injection

Outcome Measure Data

Analysis Population Description

Of 12 participants, 8 had evaluable TBR data.

Arm/Group Title	I124-NM404 Brain Metastases or GBM Imaging
Arm/Group Description	Participants injected with 185 MBq ± of 124I-CLR1404 intravenously over a period of 1 to 2 minutes, followed by a flush of 10 mL of normal saline. Subjects returned for PET/CT imaging at 6-, 24-, and 48-hours post-injection. Participants received 3 drops of potassium iodide by mouth (1 gm/ml) 1 to 24 hours prior to injection of 124I-CLR1404 and continued additional daily doses prior to each PET/CT scan for 3 consecutive days.
Measure Participants	8
24 hours	2.86 (1.77)
48 hours	2.93 (2.07)

4. Primary Outcome

Title	Tumor to Blood Pool Ratios Post-imaging for Confirmed Malignant Tumors
Description	Tumor to blood pool ratio (tumor SUVmax to superior sinus SUVmean) was calculated at each time point. Tumor to blood pool is calculated by using tumor/lesion SUVmax and dividing by blood pool SUVmean from placing a region of interest in the posterior sagittal sinus near the confluence of sinuses. Imaging performed at 24-, and 48 hours post injection.
Time Frame	24- and 48 hours post injection

Outcome Measure Data

Analysis Population Description

Of 12 participants, 8 had evaluable tumor to blood pool ratio data.

Arm/Group Title	I124-NM404 Brain Metastases or GBM Imaging
Arm/Group Description	Participants injected with 185 MBq ± of 124I-CLR1404 intravenously over a period of 1 to 2 minutes, followed by a flush of 10 mL of normal saline. Subjects returned for PET/CT imaging at 6-, 24-, and 48-hours post-injection. Participants received 3 drops of potassium iodide by mouth (1 gm/ml) 1 to 24 hours prior to injection of 124I-CLR1404 and continued additional daily doses prior to each PET/CT scan for 3 consecutive days.
Measure Participants	8
24 hours	3.35 (1.75)
48 hours	3.45 (2.15)

Adverse Events

Time Frame	Adverse event data were collected for up to 48 hours (until the time of the final scan).
Adverse Event Reporting Description	Subjects are monitored for adverse events (AEs) by the research team and reported by the principle investigator or co-investigators. Subjects are observed during the injection of 124I-NM404 and for 30 minutes after injection. Subjects are also monitored at each PET/CT scanning session. Approximately 2 - 4 weeks after injection of 124I-NM404, subjects were contacted by phone or other means and/or medical records were reviewed, if available, to assess for any AEs. AE data collection is complete.
Arm/Group Title	I124-NM404 Brain Metastases or GBM Imaging
Arm/Group Description	Participants injected with 185 MBq ± of 124I-CLR1404 intravenously over a period of 1 to 2 minutes, followed by a flush of 10 mL of normal saline. Subjects returned for PET/CT imaging at 6-, 24-, and 48-hours post-injection. Participants received 3 drops of potassium iodide by mouth (1 gm/ml) 1 to 24 hours prior to injection of 124I-CLR1404 and continued additional daily doses prior to each PET/CT scan for 3 consecutive days.
All Cause Mortality
	I124-NM404 Brain Metastases or GBM Imaging
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Serious Adverse Events
	I124-NM404 Brain Metastases or GBM Imaging
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Other (Not Including Serious) Adverse Events
	I124-NM404 Brain Metastases or GBM Imaging
	Affected / at Risk (%)	# Events
Total	0/12 (0%)

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.