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

Phase 2

Completed

Conditions: Lung Cancer
Sarcoma
High-grade Glioma
Melanoma
Head & Neck Cancer

Interventions: Drug: Fluciclatide Injection - (AH111585 (F18))

Registration Number: NCT00565721

Lead Sponsor: GE Healthcare

Brief Summary: This proof-of-concept study is designed to assess the ability of \[18F\]AH-111585 PET imaging to detect tumors and angiogenesis. Up to 30 evaluable subjects are planned to be included at up to 2 study centers in the US. Subjects are considered evaluable if they undergo administration of AH-111585 (18F) Injection, dynamic and static PET imaging, and tumor tissue acquisition. The targeted population is adult subjects at initial diagnosis or recurrence with tumors ≥2.5 cm in diameter who are scheduled to undergo resection or biopsy of the tumor as a result of routine clinical treatment. The tumors must belong to one of the following 5 types:

* High-grade glioma, including glioblastoma multiforme, anaplastic astrocytoma, and anaplastic oligodendroglioma

* Lung cancer, including small cell lung cancer and non-small cell lung cancer

* Head and neck (H\&N) tumors, including laryngeal squamous cell carcinoma, well-differentiated thyroid and oral cavity carcinoma

* Sarcoma

* Melanoma

Safety will be assessed from the rates of adverse events, changes in vital signs, changes in electrocardiogram (ECG) parameters, changes in physical examination findings, and changes in clinical laboratory findings.

Efficacy will be assessed as the correlations between parameters derived from the PET images and the reference standards. The reference standards will be immunohistology for αvβ3 integrins and other biomarkers specific for oncology and angiogenesis and from the standard of care imaging.

Measures obtained from optional DCE-CT imaging may also be used to compare the uptake and retention of \[18F\]AH-111585 in tumors obtained from the dynamic PET to assess functional status of the vascular system of the tumor.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 33

Inclusion Criteria

Not provided

Exclusion Criteria

The subject is lactating.
The subject is being treated with heparin or coumadin.
The subject has received another investigational medicinal product (IMP) within 14 days before, or will receive an IMP within 1 week after administration of AH-111585 (18F) Injection.
The subject was previously included in this study.
The subject experienced substantial changes in their medical status before all essential study procedures (including all imaging procedures and surgical excision or biopsy) are performed.
The subject has any contraindication to any of the study procedures, products used or its constituents (e.g. X-ray contrast media).
The subject has known hyper- or hypo-coagulation syndromes. Such coagulopathies include but are not limited to Von Willebrand disease, Protein C deficiency, Protein S deficiency, Hemophilia A/B/C, Factor-V Leiden, and Bernard-Soulier syndrome.
The subject is unable to lie down for 125 minutes.
The subject suffers from claustrophobia.
The subject has known diagnosis of human immunodeficiency virus (HIV) infection.
The subject has known diagnosis of hepatitis B or C infection.
The subject has known diagnosis of mental incapacitation and it affects their ability to consent.
The subject has been diagnosed with a primary or metastatic tumour lesion <2.5 cm.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fluciclatide Injection - (AH111585 (F18))	Fluciclatide Injection - (AH111585 (F18))	Using of the drug product named, AH111585 (F18) Injection. It's generic chemical name is Fluciclatide.

Primary Outcome Measures

Name	Time	Method
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)	Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.	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.
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)	Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.	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.
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)	Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.	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.
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)	Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.	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.
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)	Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.	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.
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)	Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.	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.
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)	Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.	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.

Secondary Outcome Measures

Name	Time	Method
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)	Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.	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.
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)	Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.	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.
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)	Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.	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.
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)	Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.	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.
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)	Tissue sample acquisition within 2 weeks of Fluciclatide PET scan.	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.