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
Selection of Subjects: The targeted subject population is adult subjects at initial
diagnosis or recurrence with tumours ≥2.5 cm in diameter who are scheduled to undergo
resection or biopsy of the tumour as a result of routine clinical treatment.
General Inclusion Criteria for all Subjects:
- The subject is ≥18 years old.
- The subject has been diagnostically imaged and is suspected of having a primary or
metastatic tumour lesion ≥2.5 cm of one of the following 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; H&N tumours, including laryngeal squamous cell carcinoma, and
well-differentiated thyroid and oral cavity carcinoma; sarcoma; and melanoma.
- The subject is scheduled to undergo resection or biopsy of the ≥2.5 cm 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.
- 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 AH-111585 (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.
- The subject is able and willing to comply with study procedures, and signed and dated
informed consent is obtained.
- The subject has a blood urea nitrogen value and serum creatinine value of ≤1.5 of the
upper normal limit.
- The subject has a platelet count of >75,000 x 10^6/L.
- The subject has a haemoglobin value of >9 g/dL.
- The subject has a prothrombin time and an activated partial thromboplastin time and
within normal limits.
- 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 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 10 days prior to PET imaging.
- The subject has had no open wounds within 10 days prior to study entry.
- The chosen target tumour is not within the liver.
Inclusion Criteria Specific for Subjects with High-grade Glioma:
- The subject is suspected of having supratentorial malignant primary glioma (by biopsy
or presenting MRI characteristics as determined by the subject's clinician) requiring
further surgical resection as part of the recommended treatment plan for their newly
diagnosed disease. These gliomas include glioblastoma multiforme, anaplastic
astrocytoma, and anaplastic oligodendroglioma.
- The subject has undergone recent biopsy of newly diagnosed high-grade glioma, has
recovered from the effects of surgical biopsy, and baseline on-study MRI/CT is
performed within 14 days of entry into the study.
- 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
- 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
- The subject has been diagnosed with a primary or metastatic tumour lesion <2.5 cm.