Trial Outcomes & Findings for A Proof-of-concept Study to Assess the Ability of [18F]AH-111585 PET Imaging to Detect Tumours and Angiogenesis (NCT NCT00565721)

NCT ID: NCT00565721

Last Updated: 2014-08-18

Results Overview

Correlation of the Magnitude of \[18F\]Fluciclatide Uptake and Retention by tumor tissue following intravenous administration of AH111585 (18F) Injection for the Full Analysis Set (FAS) subjects. Correlation strength was defined descriptively. 0.22 and 0.24 equals a weak positive correlation and 0.16 and 0.18 equals a negligible correlation. Three (3) of the 22 subjects did not have any αvβ3 integrin results. Ki-inp-Patlak is a graphical analysis technique based on the compartment model that uses linear regression to identify and analyze pharmacokinetics of tracers involving irreversible uptake.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 33 participants
• Primary outcome timeframe: Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.
• Results posted on: 2014-08-18

Participant Flow

A total of 33 subjects enrolled in this study. 16 subjects completed the study and 17 subjects did not.

33 subjects enrolled,16 subjects completed and 17 did not complete. The reasons why 17 subjects that did not complete the study: 2 subjects failed screening, 6 subjects were lost to followup, 1 subject the procedure had technical problems, 2 subjects discontinued due to Physician decision, and 6 subjects had other reasons for not completing.

Participant milestones

Measure	Fluciclatide Injection The patient would receive an injection of Fluciclatide (GE-135) (F18) at 10mCi (370 megabecquerels (MBq)).
Overall Study STARTED	33
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	17

Reasons for withdrawal

Measure	Fluciclatide Injection The patient would receive an injection of Fluciclatide (GE-135) (F18) at 10mCi (370 megabecquerels (MBq)).
Overall Study Screen Failure	2
Overall Study Lost to Follow-up	6
Overall Study Technical Problems	1
Overall Study Physician Decision	2
Overall Study Other reasons	6

Baseline Characteristics

A Proof-of-concept Study to Assess the Ability of [18F]AH-111585 PET Imaging to Detect Tumours and Angiogenesis

Baseline characteristics by cohort

Measure	Safety With Fluciclatide Injection n=25 Participants The patient would receive an injection of Fluciclatide (GE-135) (F18) at 10mCi (370 megabecquerels (MBq)).
Age, Continuous	50.4 years STANDARD_DEVIATION 10.09 • n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	25 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Region of Enrollment United States	24 participants n=5 Participants
Region of Enrollment United Kingdom	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.

Population: This Outcome Measure was assessed among the Full Analysis Set (FAS), 3 of the 22 Subjects did not have any αvβ3 integrin results.

Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention by tumor tissue following intravenous administration of AH111585 (18F) Injection for the Full Analysis Set (FAS) subjects. Correlation strength was defined descriptively. 0.22 and 0.24 equals a weak positive correlation and 0.16 and 0.18 equals a negligible correlation.

Three (3) of the 22 subjects did not have any αvβ3 integrin results. Ki-inp-Patlak is a graphical analysis technique based on the compartment model that uses linear regression to identify and analyze pharmacokinetics of tracers involving irreversible uptake.

Outcome measures

Measure	Correlation Between Ki_inp-Patlak and αvβ3 Optical Density n=19 Participants Correlation between Imaging parameters. The selected imaging parameters that reflected (18F) Fluciclatide tracer uptake and retention.
Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention With Quantitative Measurement of the Levels of αvβ3 (Beta-3 Integrin) Integrin Expression in Tumors. (Correlation Between Ki_inp-Patlak and αvβ3 Optical Density)	0.22 Correlation coefficient Interval -0.26 to 0.61

PRIMARY outcome

Timeframe: Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.

Population: This Outcome Measure was assessed among the Full Analysis Set (FAS), 3 of the 22 Subjects did not have any αvβ3 integrin results.

Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention by tumor tissue following intravenous administration of AH111585 (18F) Injection for the Full Analysis Set (FAS) subjects. Correlation strength was defined descriptively.

The Logan plot is the counterpart of the Patlak plot for reversible radiotracers.

Outcome measures

Measure	Correlation Between Ki_inp-Patlak and αvβ3 Optical Density n=19 Participants Correlation between Imaging parameters. The selected imaging parameters that reflected (18F) Fluciclatide tracer uptake and retention.
Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention With Quantitative Measurement of the Levels of αvβ3 Integrin Expression in Tumors. (Correlation Between VT_inp-Logan and αvβ3 Optical Density)	0.24 Correlation coefficient Interval -0.24 to 0.62

PRIMARY outcome

Timeframe: Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.

Population: This Outcome Measure was assessed among the Full Analysis Set (FAS), 3 of the 22 Subjects did not have any αvβ3 integrin results.

Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention by tumor tissue following intravenous administration of AH111585 (18F) Injection for the Full Analysis Set (FAS) subjects. Correlation strength was defined descriptively.

SUVw_55 is the standard uptake value at 55 minutes post-injection, normalized to weight.

Outcome measures

Measure	Correlation Between Ki_inp-Patlak and αvβ3 Optical Density n=19 Participants Correlation between Imaging parameters. The selected imaging parameters that reflected (18F) Fluciclatide tracer uptake and retention.
Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention With Quantitative Measurement of the Levels of αvβ3 (Beta-3 Integrin) Integrin Expression in Tumors. (Correlation Between SUVw_55 and αvβ3 Optical Density)	0.16 Correlation coefficient Interval -0.32 to 0.57

PRIMARY outcome

Timeframe: Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.

Population: This Outcome Measure was assessed among the Full Analysis Set (FAS), 3 of the 22 Subjects did not have any αvβ3 integrin results.

Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention by tumor tissue following intravenous administration of AH111585 (18F) Injection for the Renal Cell Carcinoma (RCC) subjects. Correlation strength was defined descriptively.

Twelve (12) of the 22 subjects had renal cell carcinoma (RCC) the remaining subjects did not have RCC.

SUVR_55_blood is the standard uptake value ratio (tumor-to-blood) at 55 minutes post-injection.

Outcome measures

Measure	Correlation Between Ki_inp-Patlak and αvβ3 Optical Density n=19 Participants Correlation between Imaging parameters. The selected imaging parameters that reflected (18F) Fluciclatide tracer uptake and retention.
Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention With Quantitative Measurement of the Levels of αvβ3 (Beta-3 Integrin) Integrin Expression in Tumors. (Correlation Between SUVR_55_blood and αvβ3 Optical Density)	0.18 Correlation coefficient Interval -0.3 to 0.58

PRIMARY outcome

Timeframe: Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.

Population: This Outcome Measure was assessed among the Renal Cell Carcinoma (RCC) subjects, 12 of the 22 Subjects had Renal Cell Carcinoma (RCC).

Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention by tumor tissue following intravenous administration of AH111585 (18F) Injection for the Renal Cell Carcinoma (RCC) subjects. Correlation strength was defined descriptively.

Outcome measures

Measure	Correlation Between Ki_inp-Patlak and αvβ3 Optical Density n=12 Participants Correlation between Imaging parameters. The selected imaging parameters that reflected (18F) Fluciclatide tracer uptake and retention.
Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention With Quantitative Measurement of the Levels of αvβ3 Integrin Expression in Tumors. (Correlation Between Ki_inp-Patlak and αvβ3 Optical Density)	0.49 Correlation coefficient Interval -0.14 to 0.82

PRIMARY outcome

Timeframe: Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.

Population: This Outcome Measure was assessed among the Renal Cell Carcinoma (RCC) subjects, 12 of the 22 Subjects had Renal Cell Carcinoma (RCC).

Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention by tumor tissue following intravenous administration of AH111585 (18F) Injection for the Renal Cell Carcinoma (RCC) subjects. Correlation strength was defined descriptively.

Outcome measures

Measure	Correlation Between Ki_inp-Patlak and αvβ3 Optical Density n=12 Participants Correlation between Imaging parameters. The selected imaging parameters that reflected (18F) Fluciclatide tracer uptake and retention.
Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention With Quantitative Measurement of the Levels of αvβ3 Integrin Expression in Tumors. (Correlation Between VT_inp-Logan and αvβ3 Optical Density)	0.56 Correlation coefficient Interval -0.05 to 0.85

PRIMARY outcome

Timeframe: Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.

Population: This Outcome Measure was assessed among the Renal Cell Carcinoma (RCC) subjects, 12 of the 22 Subjects had Renal Cell Carcinoma (RCC).

Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention by tumor tissue following intravenous administration of AH111585 (18F) Injection for the Renal Cell Carcinoma (RCC) subjects. Correlation strength was defined descriptively.

Outcome measures

Measure	Correlation Between Ki_inp-Patlak and αvβ3 Optical Density n=12 Participants Correlation between Imaging parameters. The selected imaging parameters that reflected (18F) Fluciclatide tracer uptake and retention.
Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention With Quantitative Measurement of the Levels of αvβ3 Integrin Expression in Tumors. (Correlation Between SUVw_55 and αvβ3 Optical Density)	0.49 Correlation coefficient Interval -0.13 to 0.83

PRIMARY outcome

Timeframe: Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.

Population: This Outcome Measure was assessed among the Renal Cell Carcinoma (RCC) subjects, 12 of the 22 Subjects had Renal Cell Carcinoma (RCC).

Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention by tumor tissue following intravenous administration of AH111585 (18F) Injection for the Renal Cell Carcinoma (RCC) subjects. Correlation strength was defined descriptively.

Outcome measures

Measure	Correlation Between Ki_inp-Patlak and αvβ3 Optical Density n=12 Participants Correlation between Imaging parameters. The selected imaging parameters that reflected (18F) Fluciclatide tracer uptake and retention.
Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention With Quantitative Measurement of the Levels of αvβ3 Integrin Expression in Tumors. (Correlation Between SUVR_55_blood and αvβ3 Optical Density)	0.44 Correlation coefficient Interval -0.2 to 0.8

SECONDARY outcome

Timeframe: Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.

Population: This Outcome Measure was assessed among the Full Analysis Set (FAS), 2 of the 22 Subjects did not have any αvβ5 integrin results.

Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention by tumor tissue following intravenous administration of AH111585 (18F) Injection for the Full Analysis Set (FAS) subjects. Correlation strength was defined descriptively. 0.60 to 0.44 equals a moderately positive correlation and 0.33 to 0.37 equals a weak positive correlation.

Two (2) of the 22 subjects did not have any αvβ5 integrin results.

Outcome measures

Measure	Correlation Between Ki_inp-Patlak and αvβ3 Optical Density n=20 Participants Correlation between Imaging parameters. The selected imaging parameters that reflected (18F) Fluciclatide tracer uptake and retention.
Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention With Quantitative Measurement of the Levels of αvβ5 Integrin Expression in Tumors. (Correlation Between Ki_inp-Patlak αvβ5 Optical Density)	0.60 Correlation coefficient Interval 0.2 to 0.82

SECONDARY outcome

Timeframe: Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.

Population: This Outcome Measure was assessed among the Full Analysis Set (FAS), 2 of the 22 Subjects did not have any αvβ5 integrin results.

Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention by tumor tissue following intravenous administration of AH111585 (18F) Injection for the Full Analysis Set (FAS) subjects. Correlation strength was defined descriptively.

Outcome measures

Measure	Correlation Between Ki_inp-Patlak and αvβ3 Optical Density n=20 Participants Correlation between Imaging parameters. The selected imaging parameters that reflected (18F) Fluciclatide tracer uptake and retention.
Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention With Quantitative Measurement of the Levels of αvβ5 Integrin Expression in Tumors. (Correlation Between VT_inp-Logan and αvβ5 Optical Density)	0.44 Correlation coefficient Interval -0.01 to 0.73

SECONDARY outcome

Timeframe: Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.

Population: This Outcome Measure was assessed among the Full Analysis Set (FAS), 2 of the 22 Subjects did not have any αvβ5 integrin results.

Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention by tumor tissue following intravenous administration of AH111585 (18F) Injection for the Full Analysis Set (FAS) subjects. Correlation strength was defined descriptively.

Outcome measures

Measure	Correlation Between Ki_inp-Patlak and αvβ3 Optical Density n=20 Participants Correlation between Imaging parameters. The selected imaging parameters that reflected (18F) Fluciclatide tracer uptake and retention.
Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention With Quantitative Measurement of the Levels of αvβ5 Integrin Expression in Tumors. (Correlation Between SUVw_55 and αvβ5 Optical Density)	0.33 Correlation coefficient Interval -0.14 to 0.67

SECONDARY outcome

Timeframe: Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.

Population: This Outcome Measure was assessed among the Full Analysis Set (FAS), 2 of the 22 Subjects did not have any αvβ5 integrin results.

Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention by tumor tissue following intravenous administration of AH111585 (18F) Injection for the Full Analysis Set (FAS) subjects. Correlation strength was defined descriptively.

Outcome measures

Measure	Correlation Between Ki_inp-Patlak and αvβ3 Optical Density n=20 Participants Correlation between Imaging parameters. The selected imaging parameters that reflected (18F) Fluciclatide tracer uptake and retention.
Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention With Quantitative Measurement of the Levels of αvβ5 Integrin Expression in Tumors. (Correlation Between SUVR_55_blood and αvβ5 Optical Density)	0.37 Correlation coefficient Interval -0.1 to 0.69

SECONDARY outcome

Timeframe: Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.

Population: This Outcome Measure was assessed among the Renal Cell Carcinoma (RCC) subjects, 12 of the 22 Subjects had Renal Cell Carcinoma (RCC).

Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention by tumor tissue following intravenous administration of AH111585 (18F) Injection for the Renal Cell Carcinoma (RCC) subjects. Correlation strength was defined descriptively.

Outcome measures

Measure	Correlation Between Ki_inp-Patlak and αvβ3 Optical Density n=12 Participants Correlation between Imaging parameters. The selected imaging parameters that reflected (18F) Fluciclatide tracer uptake and retention.
Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention With Quantitative Measurement of the Levels of αvβ5 Integrin Expression in Tumors. (Correlation Between Ki_inp-Patlak and αvβ5 Optical Density)	0.90 Correlation coefficient Interval 0.67 to 0.97

SECONDARY outcome

Timeframe: Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.

Population: This Outcome Measure was assessed among the Renal Cell Carcinoma (RCC) subjects, 12 of the 22 Subjects had Renal Cell Carcinoma (RCC).

Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention by tumor tissue following intravenous administration of AH111585 (18F) Injection for the Renal Cell Carcinoma (RCC) subjects. Correlation strength was defined descriptively.

Outcome measures

Measure	Correlation Between Ki_inp-Patlak and αvβ3 Optical Density n=12 Participants Correlation between Imaging parameters. The selected imaging parameters that reflected (18F) Fluciclatide tracer uptake and retention.
Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention With Quantitative Measurement of the Levels of αvβ5 Integrin Expression in Tumors. (Correlation Between VT_inp-Logan and αvβ5 Optical Density)	0.78 Correlation coefficient Interval 0.34 to 0.93

SECONDARY outcome

Timeframe: Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.

Population: This Outcome Measure was assessed among the Renal Cell Carcinoma (RCC) subjects, 12 of the 22 Subjects had Renal Cell Carcinoma (RCC).

Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention by tumor tissue following intravenous administration of AH111585 (18F) Injection for the Renal Cell Carcinoma (RCC) subjects. Correlation strength was defined descriptively.

Outcome measures

Measure	Correlation Between Ki_inp-Patlak and αvβ3 Optical Density n=12 Participants Correlation between Imaging parameters. The selected imaging parameters that reflected (18F) Fluciclatide tracer uptake and retention.
Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention With Quantitative Measurement of the Levels of αvβ5 Integrin Expression in Tumors. (Correlation Between SUVw_55 and αvβ5 Optical Density)	0.57 Correlation coefficient Interval -0.03 to 0.85

SECONDARY outcome

Timeframe: Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.

Population: This Outcome Measure was assessed among the Renal Cell Carcinoma (RCC) subjects, 12 of the 22 Subjects had Renal Cell Carcinoma (RCC).

Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention by tumor tissue following intravenous administration of AH111585 (18F) Injection for the Renal Cell Carcinoma (RCC) subjects. Correlation strength was defined descriptively.

Outcome measures

Measure	Correlation Between Ki_inp-Patlak and αvβ3 Optical Density n=12 Participants Correlation between Imaging parameters. The selected imaging parameters that reflected (18F) Fluciclatide tracer uptake and retention.
Correlation of the Magnitude of [18F]Fluciclatide Uptake and Retention With Quantitative Measurement of the Levels of αvβ5 Integrin Expression in Tumors. (Correlation Between SUVR_55_blood and αvβ5 Optical Density)	0.74 Correlation coefficient Interval 0.27 to 0.92

Adverse Events

Fluciclatide Injection

Serious events: 5 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Measure	Fluciclatide Injection n=25 participants at risk The patient would receive an injection of Fluciclatide (GE-135) (F18) at 10mCi (370 megabecquerels (MBq)).
Blood and lymphatic system disorders Anemia	4.0% 1/25 • Number of events 1 • Up to 6 weeks post administration of Fluciclatide (GE-135) (18F) Injection at 10 mCi [370 megabecquerels (MBq)].
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioblastoma Multiforme (GBM)	4.0% 1/25 • Number of events 1 • Up to 6 weeks post administration of Fluciclatide (GE-135) (18F) Injection at 10 mCi [370 megabecquerels (MBq)].
Blood and lymphatic system disorders Idiopathic Thrombocytopenic Purpura (ITP)	4.0% 1/25 • Number of events 1 • Up to 6 weeks post administration of Fluciclatide (GE-135) (18F) Injection at 10 mCi [370 megabecquerels (MBq)].
Respiratory, thoracic and mediastinal disorders Pneumothorax	4.0% 1/25 • Number of events 1 • Up to 6 weeks post administration of Fluciclatide (GE-135) (18F) Injection at 10 mCi [370 megabecquerels (MBq)].
Injury, poisoning and procedural complications Renal Injury	4.0% 1/25 • Number of events 1 • Up to 6 weeks post administration of Fluciclatide (GE-135) (18F) Injection at 10 mCi [370 megabecquerels (MBq)].
Skin and subcutaneous tissue disorders Subcutaneous Emphysema	4.0% 1/25 • Number of events 1 • Up to 6 weeks post administration of Fluciclatide (GE-135) (18F) Injection at 10 mCi [370 megabecquerels (MBq)].

Other adverse events

Measure	Fluciclatide Injection n=25 participants at risk The patient would receive an injection of Fluciclatide (GE-135) (F18) at 10mCi (370 megabecquerels (MBq)).
Gastrointestinal disorders Gastrointestinal Disorders	12.0% 3/25 • Number of events 3 • Up to 6 weeks post administration of Fluciclatide (GE-135) (18F) Injection at 10 mCi [370 megabecquerels (MBq)].
General disorders General disorders and administration site conditions	20.0% 5/25 • Number of events 6 • Up to 6 weeks post administration of Fluciclatide (GE-135) (18F) Injection at 10 mCi [370 megabecquerels (MBq)].
Infections and infestations Infections and Infestations	12.0% 3/25 • Number of events 3 • Up to 6 weeks post administration of Fluciclatide (GE-135) (18F) Injection at 10 mCi [370 megabecquerels (MBq)].
Investigations Investigations	12.0% 3/25 • Number of events 4 • Up to 6 weeks post administration of Fluciclatide (GE-135) (18F) Injection at 10 mCi [370 megabecquerels (MBq)].
Respiratory, thoracic and mediastinal disorders Respiratory	8.0% 2/25 • Number of events 2 • Up to 6 weeks post administration of Fluciclatide (GE-135) (18F) Injection at 10 mCi [370 megabecquerels (MBq)].

Additional Information

Paul Gordon, PhD

GE Healthcare

Phone: 011-47-2318-5822

Email: paul.gordon@ge.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place