A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of RX108 in Patients with Advanced or Metastatic Solid Tumours.

Exclusion Criteria28

• Any clinically significant cardiovascular disease including but not limited to:
• New York Heart Association Class II or greater congestive heart failure;
• History of ischaemic cardiac disease, myocardial infarction or unstable angina within 6 months prior to Day 1;
• Hypertrophic obstructive cardiomyopathy;
• History of stroke or transient ischemic attack within 6 months prior to Day 1;
• Presence or history of cardiac conduction abnormalities (increased PR or QRS), atrioventricular block or arrhythmias including intermittent complete heart block or second degree atrioventricular block, history of Stokes-Adams attacks, ventricular tachycardia, ventricular fibrillation or supraventricular arrhythmias;
• Use of the following concurrent medications: beta blockers, digoxin, calcium channel blockers, amiodarone, flecainide, quinidine, and any other anti-arrhythmic.
• Known contra-indication, intolerance or hypersensitivity to digoxin
• Inadequate hematologic and organ function, defined by the following
• Absolute neutrophil count < 1.5x109/L, haemoglobin < 9 g/dL
• Total bilirubin 1.5 x the upper limit of normal (ULN) with the following exception: Patients with known Gilbert disease who have serum bilirubin level > 3 x the ULN and normal Aspartate Transaminase (AST)/ Alanine Transaminase (ALT) may be enrolled.
• AST and/or ALT > 2.5 x the ULN with the following exception: Patients with documented liver metastases may have AST and/or ALT levels > 5 x the ULN.
• Serum creatinine > 1.5 x the ULN with the following exception: A creatinine clearance of 50 mL/min based on a calculated glomerular filtration rate (GFR) (e.g. Cockcroft-Gault formula)
• International normalized ratio (INR) > 1.5 x the ULN or activated partial thromboplastin time (aPTT) > 1.5 x the ULN. The INR applies only to patients who do not receive therapeutic anti-coagulation.
• Serum electrolytes (Sodium, Calcium, Potassium, Magnesium) within normal limits.
• Severe respiratory disease.
• Any unapproved concurrent therapies for cancer (complementary or alternative therapies), or any anti-cancer therapy, including chemotherapy, hormonal therapy, biologic therapy, radiotherapy, or herbal therapy within 4 weeks prior to initiation of study treatment with the following exceptions:
• Hormonal therapy with gonadotropin-releasing hormone agonists for prostate cancer at stable doses for at least 30 days prior to study entry
• Hormone-replacement therapy or oral contraceptives at stable doses for at least 30 days prior to study entry
• Palliative radiation to bone metastases acceptable within 2 weeks prior to Day 1
• AEs from prior anti-cancer therapy that have not resolved to CTCAE Grade 1, except for alopecia.
• Clinically significant active infection.
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.
• Known human immunodeficiency virus infection.
• Pregnant (positive pregnancy test) or lactating women.
• Active or untreated brain metastasis.
• Inability to comply with study and follow-up procedures.
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the Investigator’s opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.