An open-label, multi-centre Phase I study of the safety and tolerability of intravenously (IV) infused PG545 in patients with advanced solid tumours

Exclusion Criteria12

• Clinically significant non-malignant disease including, but not limited to, major surgery within 6 weeks of randomisation, active clinically significant infection, myocardial infarction within 6 months prior to randomisation, cerebrovascular event or transient ischaemic attack within 12 months prior to randomisation or clinically significant gastrointestinal bleeding within 12 months prior to randomisation. Anti-cancer therapy within 4 weeks of Cycle 1 day 1 (excluding GnRH agonists for prostate cancer). Palliative radiation for bone metastases within 2 weeks of Cycle 1 day 1.
• Active CNS metastases. Subjects with prior CNS metastases treated by surgery and/or stereotactic irradiation are eligible providing they have no evidence of active disease at screening. Subjects with prior CNS metastases treated with only whole brain radiation therapy are ineligible.
• Subjects with uncontrolled diabetes.
• History of allergy and / or hypersensitivity and / or other clinically significant adverse drug reaction to heparin or other anti-coagulant agents.
• History of immune-mediated thrombocytopaenia or other platelet abnormalities or other hereditary or acquired coagulopathies, or laboratory evidence of anti-heparin antibodies, or any previous history of having tested positive for anti-heparin antibodies.
• Concomitant use of aspirin (> 150 mg/day), non steroidal anti-inflammatory drugs (except COX-2 selective inhibitors), vitamin K antagonists (other than low-dose prophylactic use), heparin within two weeks prior to randomisation, or other anti-platelet drugs (e.g. abciximab, clopidogrel, dipyridamole, ticlopidine and tirofiban). Low-dose aspirin (= 150 mg/day) and low dose prophylactic vitamin K antagonists (e.g. warfarin = 1 mg/day) are permitted as concomitant medications.
• History of severe allergic, anaphylactic or other significant adverse reaction to radiographic contrast media (iodinated or non-iodinated), which cannot be managed by pre treatment with agents such as steroids or anti histamines, and which, in the opinion of the Investigator, renders the subject unsuitable for routine CT or MRI scanning. Subjects who are contra-indicated for CT or MRI scanning for other reasons (e.g. ferromagnetic implants, profound claustrophobia), should not be enrolled.
• Known seropositivity to the human immunodeficiency virus (HIV).
• Women who are pregnant or breast-feeding.
• Women of child-bearing potential and male subjects who are partners of women of childbearing potential who are unable or unwilling to practice a highly effective means of contraception. Effective birth control includes: a) birth control pills, depot progesterone, or an intrauterine device plus one barrier method, or b) two barrier methods. Effective barrier methods are: male and female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm).
• Active substance abuse, including alcohol, which, in the opinion of the Investigator, risks impairing the ability of the subject to comply with the protocol.
• Subjects who have received an investigational agent within 28 days prior to Cycle 1 Day 1; or are currently participating in any other clinical study or research project which involves administration of a pharmaceutical product or experimental treatment, or which involves protocol-specified laboratory tests, imaging studies or other investigations.