Trial Outcomes & Findings for FMISO PET Study of Glioblastoma (NCT NCT02076152)

NCT ID: NCT02076152

Last Updated: 2021-07-30

Results Overview

Recruitment status

COMPLETED

Study phase

Target enrollment

11 participants

Primary outcome timeframe

Baseline and day 14 scans

Results posted on

2021-07-30

Participant Flow

Participant milestones

Participant milestones
Measure	FMISO PET & MRI Group 1 Bevacizumab: * Bevacizumab will be administered at a dose of 10 mg/kg i.v. every 14 days per standard of care and the drug label. A cycle is defined as 28 days (1 month). -FMISO PET Scan * FMISO will be intravenously injected at a dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in \< 15 mL. The IV will remain in place for injection of the gadolinium for the MRI scan. There will be one injection of FMISO in the PET protocol. Approximately 90 minutes after the injection, the PET scan will begin. * The PET scan will be approximately 60-75 minutes. -MRI * Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs. FMISO PET MRI: MR scans will be performed with the same sequences and in the same order during each visit, including T1- and T2-weighted volumetric images, fluid attenuated inversion recovery (FLAIR), contrast agent enhanced T1-weighted permeability, diffusion tensor imaging (DTI), T2/T2\*-weighted perfusion scans, and MR Spectroscopy. The "Autoalign" package available from the manufacturer will be used to achieve the same slice prescription in the same patient at each visit. Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs. Bevacizumab: A cycle is defined as 28 days (1 month). The study duration is 12 months (12 cycles). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician.	FMISO PET & MRI Group 2 Bevacizumab + CCNU: * Bevacizumab administered at dose of 10 mg/kg IV every 14 days per standard of care and drug label. Cycle defined as 28 days (1 month). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician. * CCNU administered at dose of 110 mg/m2 every 42 days per standard of care and drug label. Cycle defined as 28 days (1 month). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician. -FMISO PET Scan * FMISO intravenously injected at dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in \< 15 mL. IV will remain in place for injection of gadolinium for MRI scan. One injection of FMISO in PET protocol. Approximately 90 min after injection, PET scan will begin. * PET scan will be approximately 60-75 minutes \- MRI * Each MRI will last 60-75 minutes vs 45 minutes for standard brain MRIs. FMISO PET MRI: MR scans will be performed with the same sequences and in the same order during each visit, including T1- and T2-weighted volumetric images, fluid attenuated inversion recovery (FLAIR), contrast agent enhanced T1-weighted permeability, diffusion tensor imaging (DTI), T2/T2\*-weighted perfusion scans, and MR Spectroscopy. The "Autoalign" package available from the manufacturer will be used to achieve the same slice prescription in the same patient at each visit. Each MRI will last 60-75 minutes vs 45 minutes for standard brain MRIs.
Overall Study STARTED	2	9
Overall Study COMPLETED	2	9
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

FMISO PET Study of Glioblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FMISO PET & MRI Group 1 n=2 Participants Bevacizumab: * Bevacizumab will be administered at a dose of 10 mg/kg i.v. every 14 days per standard of care and the drug label. A cycle is defined as 28 days (1 month). -FMISO PET Scan * FMISO will be intravenously injected at a dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in \< 15 mL. The IV will remain in place for injection of the gadolinium for the MRI scan. There will be one injection of FMISO in the PET protocol. Approximately 90 minutes after the injection, the PET scan will begin. * The PET scan will be approximately 60-75 minutes. \- MRI * Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs. FMISO PET MRI: MR scans will be performed with the same sequences and in the same order during each visit, including T1- and T2-weighted volumetric images, fluid attenuated inversion recovery (FLAIR), contrast agent enhanced T1-weighted permeability, diffusion tensor imaging (DTI), T2/T2\*-weighted perfusion scans, and MR Spectroscopy. The "Autoalign" package available from the manufacturer will be used to achieve the same slice prescription in the same patient at each visit. Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs. Bevacizumab: A cycle is defined as 28 days (1 month). The study duration is 12 months (12 cycles). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician.	FMISO PET & MRI Group 2 n=9 Participants Bevacizumab + CCNU: * Bevacizumab administered at dose of 10 mg/kg IV every 14 days per standard of care and drug label. Cycle defined as 28 days (1 month). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician. * CCNU administered at dose of 110 mg/m2 every 42 days per standard of care and drug label. Cycle defined as 28 days (1 month). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician. -FMISO PET Scan * FMISO intravenously injected at dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in \< 15 mL. IV will remain in place for injection of gadolinium for MRI scan. One injection of FMISO in PET protocol. Approximately 90 min after injection, PET scan will begin. * PET scan will be approximately 60-75 minutes \- MRI * Each MRI will last 60-75 minutes vs 45 minutes for standard brain MRIs. FMISO PET MRI: MR scans will be performed with the same sequences and in the same order during each visit, including T1- and T2-weighted volumetric images, fluid attenuated inversion recovery (FLAIR), contrast agent enhanced T1-weighted permeability, diffusion tensor imaging (DTI), T2/T2\*-weighted perfusion scans, and MR Spectroscopy. The "Autoalign" package available from the manufacturer will be used to achieve the same slice prescription in the same patient at each visit. Each MRI will last 60-75 minutes vs 45 minutes for standard brain MRIs.	Total n=11 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Age, Continuous	75 years n=5 Participants	54 years n=7 Participants	58 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and day 14 scans

Population: Group 1 (Bevacizumab monotherapy) enrolled 2 patients. Group 2 (Bevacizumab+Lomustine) enrolled 9 patients. Any analysis per arm would be meaningless so the outcome data for both groups were lumped together. There was no pre-specified analysis plan to analyze the cohorts separately. Due to production challenges with FMISO, only 4 patients underwent all 3 FMISO-PET scans: baseline, day 14, and day 28. All 4 patients were in Group 2. The remaining 7 patients had MRI scans alone at those visits.

Outcome measures

Outcome measures
Measure	FMISO PET & MRI (Combined Groups) n=11 Participants Bevacizumab + CCNU: * Bevacizumab administered at dose of 10 mg/kg IV every 14 days per standard of care and drug label. Cycle defined as 28 days (1 month). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician. * CCNU administered at dose of 110 mg/m2 every 42 days per standard of care and drug label. Cycle defined as 28 days (1 month). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician. -FMISO PET Scan * FMISO intravenously injected at dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in \< 15 mL. IV will remain in place for injection of gadolinium for MRI scan. One injection of FMISO in PET protocol. Approximately 90 min after injection, PET scan will begin. * PET scan will be approximately 60-75 minutes \- MRI * Each MRI will last 60-75 minutes vs 45 minutes for standard brain MRIs. FMISO PET MRI: MR scans will be performed with the same sequences and in the same order during each visit, including T1- and T2-weighted volumetric images, fluid attenuated inversion recovery (FLAIR), contrast agent enhanced T1-weighted permeability, diffusion tensor imaging (DTI), T2/T2\*-weighted perfusion scans, and MR Spectroscopy. The "Autoalign" package available from the manufacturer will be used to achieve the same slice prescription in the same patient at each visit. Each MRI will last 60-75 minutes vs 45 minutes for standard brain MRIs.
Change in Tumor Blood Flow/Perfusion Baseline	1.00 mL/100 g/min Interval 0.83 to 1.36
Change in Tumor Blood Flow/Perfusion Day 14 (Week 2)	1.15 mL/100 g/min Interval 0.92 to 1.28

PRIMARY outcome

Timeframe: Baseline and day 14 scans

In this research study, the investigators are using FMISO-PET and MRI scans to explore the delivery of bevacizumab to the blood vessels in patient's with recurrent glioblastoma before and after treatment. Regional hypoxic volume (HV) was determined by thresholding the ratio of the standardized uptake values (SUV) of FMISO in the brain to cerebellum above 1.2. Since some patients had multiple tumors, we identified the HV region within the union of each contrast enhancing region of interest (ROI) and its surrounding FLAIR ROI, so individual tumors could be evaluated separately. HV represents the magnitude of hypoxia within each tumor.

Outcome measures

Outcome measures
Measure	FMISO PET & MRI (Combined Groups) n=9 Participants Bevacizumab + CCNU: * Bevacizumab administered at dose of 10 mg/kg IV every 14 days per standard of care and drug label. Cycle defined as 28 days (1 month). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician. * CCNU administered at dose of 110 mg/m2 every 42 days per standard of care and drug label. Cycle defined as 28 days (1 month). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician. -FMISO PET Scan * FMISO intravenously injected at dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in \< 15 mL. IV will remain in place for injection of gadolinium for MRI scan. One injection of FMISO in PET protocol. Approximately 90 min after injection, PET scan will begin. * PET scan will be approximately 60-75 minutes \- MRI * Each MRI will last 60-75 minutes vs 45 minutes for standard brain MRIs. FMISO PET MRI: MR scans will be performed with the same sequences and in the same order during each visit, including T1- and T2-weighted volumetric images, fluid attenuated inversion recovery (FLAIR), contrast agent enhanced T1-weighted permeability, diffusion tensor imaging (DTI), T2/T2\*-weighted perfusion scans, and MR Spectroscopy. The "Autoalign" package available from the manufacturer will be used to achieve the same slice prescription in the same patient at each visit. Each MRI will last 60-75 minutes vs 45 minutes for standard brain MRIs.
Change in Tumor Hypoxic Volume Baseline	45 percentage of total tumor area Interval 40.0 to 74.0
Change in Tumor Hypoxic Volume Day 14 (Week 2)	62 percentage of total tumor area Interval 43.0 to 88.0

SECONDARY outcome

Timeframe: Baseline and day 14

The DCE-MRI data were processed using in-house custom software written in MATLAB to obtain maps of Ktrans based on the 2-parameter Tofts model. Population-level arterial input functions (AIFs) were used for DCE analysis; DCE was used only to calculate Ktrans. Median tumor values for Ktrans were calculated from the contrast enhancing region of interest (ROI). Higher value is more permeability.

Outcome measures

Outcome measures
Measure	FMISO PET & MRI (Combined Groups) n=11 Participants Bevacizumab + CCNU: * Bevacizumab administered at dose of 10 mg/kg IV every 14 days per standard of care and drug label. Cycle defined as 28 days (1 month). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician. * CCNU administered at dose of 110 mg/m2 every 42 days per standard of care and drug label. Cycle defined as 28 days (1 month). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician. -FMISO PET Scan * FMISO intravenously injected at dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in \< 15 mL. IV will remain in place for injection of gadolinium for MRI scan. One injection of FMISO in PET protocol. Approximately 90 min after injection, PET scan will begin. * PET scan will be approximately 60-75 minutes \- MRI * Each MRI will last 60-75 minutes vs 45 minutes for standard brain MRIs. FMISO PET MRI: MR scans will be performed with the same sequences and in the same order during each visit, including T1- and T2-weighted volumetric images, fluid attenuated inversion recovery (FLAIR), contrast agent enhanced T1-weighted permeability, diffusion tensor imaging (DTI), T2/T2\*-weighted perfusion scans, and MR Spectroscopy. The "Autoalign" package available from the manufacturer will be used to achieve the same slice prescription in the same patient at each visit. Each MRI will last 60-75 minutes vs 45 minutes for standard brain MRIs.
Blood Vessel Permeability (Ktrans Change on MRI Scan) Baseline	0.14 1/min Interval 0.06 to 0.26
Blood Vessel Permeability (Ktrans Change on MRI Scan) Day 14 (Week 2)	0.08 1/min Interval 0.03 to 0.13

SECONDARY outcome

Timeframe: Baseline and day 14 scans

This outcome measure looks at what blood flow was doing in tumor regions that were hypoxic. This outcome measured blood flow to the tumor using an MRI technique called dynamic susceptibility contrast enhancement that measures how fast injected contrast material flows through the tumor. This outcome specifically explored how blood flow to the tumor influenced tumor hypoxia.

Outcome measures

Outcome measures
Measure	FMISO PET & MRI (Combined Groups) n=11 Participants Bevacizumab + CCNU: * Bevacizumab administered at dose of 10 mg/kg IV every 14 days per standard of care and drug label. Cycle defined as 28 days (1 month). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician. * CCNU administered at dose of 110 mg/m2 every 42 days per standard of care and drug label. Cycle defined as 28 days (1 month). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician. -FMISO PET Scan * FMISO intravenously injected at dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in \< 15 mL. IV will remain in place for injection of gadolinium for MRI scan. One injection of FMISO in PET protocol. Approximately 90 min after injection, PET scan will begin. * PET scan will be approximately 60-75 minutes \- MRI * Each MRI will last 60-75 minutes vs 45 minutes for standard brain MRIs. FMISO PET MRI: MR scans will be performed with the same sequences and in the same order during each visit, including T1- and T2-weighted volumetric images, fluid attenuated inversion recovery (FLAIR), contrast agent enhanced T1-weighted permeability, diffusion tensor imaging (DTI), T2/T2\*-weighted perfusion scans, and MR Spectroscopy. The "Autoalign" package available from the manufacturer will be used to achieve the same slice prescription in the same patient at each visit. Each MRI will last 60-75 minutes vs 45 minutes for standard brain MRIs.
Tumor Blood Flow Measured by MRI Perfusion Baseline	1.00 mL/100 g/min Interval 0.83 to 1.36
Tumor Blood Flow Measured by MRI Perfusion Day 14 (Week 2)	1.15 mL/100 g/min Interval 0.92 to 1.28

Adverse Events

FMISO PET & MRI Group 1

Serious events: 0 serious events

Other events: 0 other events

Deaths: 2 deaths

FMISO PET & MRI Group 2

Serious events: 0 serious events

Other events: 0 other events

Deaths: 8 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Elizabeth Gerstner, MD

Massachusetts General Hospital

Phone: 617-724-2887

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place