A Proof-of-concept Study to Assess the Ability of [18F]AH-111585 PET Imaging to Detect Tumours and Angiogenesis
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
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.
Head & Neck Cancer
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||A Phase 2, Open-label, Proof-of-concept Study to Assess the Ability to Detect Tumours and Angiogenesis Via the Expression of ανβ3/5 Integrin Receptors by [18F]AH-111585 PET Imaging|
- To correlate the magnitude of [18F]AH-111585 uptake and retention with quantitative measurement of the levels of ανβ3 integrin expression in tumours. [ Time Frame: Dynamic PET & Static PET immediately after administration of agent in succession; Tissue sample acquisition within 2 weeks of PET imaging. IHC of ανβ3 integrin in an ongoing manner upon receipt at TMD. ] [ Designated as safety issue: No ]
- To correlate tumour perfusion and vascular permeability in tumour tissue (as measured by dynamic contrast enhanced computed tomography [DCE-CT]) with the magnitude of uptake and retention of [18F]AH-111585. [ Time Frame: Tissue sample acquisition within 2 weeks of PET imaging IHC of Oncology & angiogenic biomarkers in an ongoing manner upon receipt at TMD. DCE-CT within 2 weeks of PET and prior to tissue sample. ] [ Designated as safety issue: No ]
- To correlate [18F]AH-111585 accumulation in tumours obtained from PET images to the expression of VEGF; VEGFr; AKT and p-AKT; MAPK and p-MAPK; and MVD in tumours by means of immunohistologic analysis of tumour tissue samples. [ Time Frame: Tissue sample acquisition within 2 weeks of PET imaging IHC of Oncology & angiogenic biomarkers in an ongoing manner upon receipt at TMD. ] [ Designated as safety issue: No ]
- To obtain preliminary data on the feasibility of detection of both primary and metastatic tumour lesions in particular tumour types using [18F]AH-111585 PET as compared to standard of care modalities. [ Time Frame: Dynamic PET & Static PET immediately after administration of agent in succession ] [ Designated as safety issue: No ]
- To assess the safety of a single intravenous administration of a maximum activity of 375 MBq [18F]AH-111585 in subjects with solid tumours. [ Time Frame: All blood samples at assigned time-points throughout the schedule of events. Serum samples at baseline, + 3 weeks and +6 weeks from PET imaging. ] [ Designated as safety issue: Yes ]
Biospecimen Retention: Samples Without DNA
Fresh Frozen and paraffin embedded sectioned samples from resected or biopsied tumor tissue in slide format; whole blood samples; separated serum samples
|Study Start Date:||November 2007|
|Study Completion Date:||September 2012|
|Primary Completion Date:||October 2011 (Final data collection date for primary outcome measure)|