E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult subjects with Primary or metastatic tumour lesion of one of the following types: high-grade glioma, including GBM, anaplastic astrocytoma, and anaplastic oligodendroglioma; lung cancer, including SCLC and NSCLC; H&N tumours, including laryngeal squamous cell carcinoma, and well-differentiated thyroid and oral cavity carcinoma; sarcoma; and melanoma; or having a primary or metastatic RCC tumour. |
|
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To correlate the magnitude of [18F]AH111585 uptake and retention with quantitative measurement of the levels of avb3 integrin expression in tumours. |
|
E.2.2 | Secondary objectives of the trial |
(1) To correlate tumour perfusion and vascular permeability in tumour tissue with the magnitude of uptake and retention of IMP. (2) To correlate IMP accumulation in tumours obtained from positron emission tomography (PET) images to the expression of vascular endothelial growth factor (VEGF); VEGF receptor (VEGFr); protein kinase B (AKT) and phosphorylated AKT; mitogen-activated protein kinase (MAPK) and phosphorylated MAPK; and microvessel density in tumours by means of immuno-histologic analysis of tumour tissue samples. (3) To obtain preliminary data on the feasibility of detection of both primary and metastatic tumour lesions in particular tumour types using IMP PET as compared to standard of care modalities (e.g. [18F]FDG-PET, contrast-enhanced static computed tomography, magnetic resonance imaging, bone scintigraphy). (4) To assess the safety of a single intravenous administration of a maximum activity of 370 MBq IMP in subjects with solid tumours. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- The subject has been diagnostically imaged and is suspected of having a primary or metastatic tumour lesion of one of the following types: high-grade glioma, including GBM, anaplastic astrocytoma, and anaplastic oligodendroglioma; lung cancer, including SCLC and NSCLC; H&N tumours, including laryngeal squamous cell carcinoma, and well-differentiated thyroid and oral cavity carcinoma; sarcoma; and melanoma; or having a primary or metastatic RCC tumour. - The subject’s tumour is greater than or equal to 2.0cm in diameter except for thyroid carcinoma (greater than or equal to 1.5 cm). - The chosen target tumour is not within the liver. - The subject is scheduled to undergo resection or biopsy of the target tumour as a result of routine clinical treatment. - The subject is scheduled to undergo or has received standard of care diagnostic imaging work-up (following the study centre’s routine procedures), e.g. CT with or without contrast, MRI with or without contrast, bone scintigraphy, X-ray, or FDG-PET. - The subject has the following baseline laboratory parameters: blood urea nitrogen (BUN) value and serum creatinine (sCr) value of less than or equal to 1.5 of the upper normal limit; prothrombin time (PTT) and an activated partial thromboplastin time (aPTT) within normal limits; platelet count of greater than or equal to 150,000 x 10exp6/L; and haemoglobin value of greater than 9 g/dL. - The subject has a clinically acceptable (as judged by the investigator) physical examination at screening and is capable of self-care, i.e. Eastern Cooperative Oncology Group (ECOG) performance status is 0 to 2, such that the subject has a high chance to complete the study. - The subject has not received any anti-angiogenic agents (e.g. bevacuzimab, sorafenib, sunitinib) within 60 days prior to PET imaging. - Female subjects need to be either surgically sterile (has had a documented bilateral oophorectomy and/or documented hysterectomy), post menopausal (cessation of menses for more than 1 year), or if of childbearing potential the results of a serum pregnancy test performed within 24 hours must be negative and with the result known before administration of AH111585 (18F) Injection. Female subjects of reproductive potential should also employ an effective method of birth control. Barrier contraceptives must be used throughout the study in both sexes. |
|
E.4 | Principal exclusion criteria |
- The subject has received another investigational medicinal product (IMP) within 14 days before, or will receive an IMP within 1 week after administration of AH111585 (18F) Injection. - 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 has known diagnosis of human immunodeficiency virus (HIV) or hepatitis B or C infection. - The subject is unable to lie down for 125 minutes. - The subject is being treated with heparin or coumadin. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint: Correlation of the quantitative uptake of [18F]AH111585 measured by PET to the quantitative measurement of staining intensity of immuno-histologic analysis of tumour tissue (resection or biopsy) samples for avb3 integrin receptors.
Safety: Safety endpoints include the occurrence of one or more treatment-emergent AEs from administration of [18F]AH111585 throughout the study period, and changes in blood chemistry (pre and post IMP administration), haematology coagulation, vital signs, ECG, injection site and physical examination findings. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |