Dose Escalation Study With Expansion to Evaluate Safety, Tolerability, Pharmacokinetics & Pharmacodynamics of CCT3833

Exclusion Criteria

• •Patients who meet ANY of the following criteria will not be eligible to participate.
• •Patients who have had any of the following within the last 4 weeks:
• •1. Radiotherapy (except for palliative reasons), endocrine therapy (except luteinizing hormone releasing hormone (LHRH) agonists for prostate cancer), immunotherapy or chemotherapy (6 weeks for nitrosoureas, Mitomycin-C and 4 weeks for other investigational medicinal products (IMP)) before treatment. (For patients recruited to Part B (dose expansion) from Part A (dose escalation), prior treatment with CCT3833 during Part A (dose escalation) is permissible.)
• •2. Major surgery within the last four weeks.
• •3. Has been a participant in another interventional research study (involving an IMP) within the last 4 weeks, or plans to participate in one whilst taking part in this study. Participation in an observational study would be acceptable.
• •Patients who have any of the following:
• •4. High medical risk because of non-malignant systemic disease including active, uncontrolled infection.
• •5. Known allergy to any pharmaceutical excipients.
• •6. Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV). Testing for these viruses is not mandatory.
• •7. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• •1. History or presence of ventricular tachyarrhythmia.
• •3. Repeated presence of a prolonged QTc interval \> 450 ms at baseline (as calculated by Fridericia method).
• •4. Unstable angina pectoris or acute myocardial infarction in the last 12 months prior to starting study drug.
• •5. Other clinically significant heart disease (e.g., symptomatic congestive heart failure (LVEF \< 50%); uncontrolled arrhythmia; history of labile hypertension or poor compliance with an antihypertensive regimen).
• •8. Uncontrolled hypertension that remains uncontrolled on \> 1 antihypertensive agent.
• •9. Symptomatic brain metastases (if present they must have been stable for \> 3 months). Such patients must not be requiring systemic corticosteroid or enzyme-inducing anticonvulsant therapy.
• •10. Inability to take oral medication; impairment of GI function or GI disease that could interfere with drug absorption.
• •11. Have taken potent inducers/inhibitors of CYP3A4 and CYP2C8 liver enzymes within 2 weeks of the first administration of study drug, or have conditions that require the concomitant usage of such drugs during the course of the study.
• •12. Are taking warfarin as an oral anticoagulant; patients anticoagulated with low molecular weight heparin are not excluded from the trial.
• •13. Female patients who are pregnant or lactating, or have the ability to become pregnant. However, those female patients who have a negative serum or urine pregnancy test before enrolment and are using highly-effective contraception during the study and for 6 months afterwards, are considered eligible. Highly-effective contraception methods include:
• •1. Total abstinence.
• •2. Male or female sterilization.
• •3. A combination of any two of the following:
• •i. Oral, injected or implanted hormonal contraception. ii. Placement of an intrauterine device (IUD) or intrauterine system (IUS). iii. Barrier methods of contraception: condom or diaphragm with spermicidal foam/gel/film/cream/vaginal suppository.
• •14. Male patients with partners of child-bearing potential, unless they agree to take measures not to father children by using one form of highly effective contraception as defined above, during the study and for 6 months afterwards. Men with pregnant or lactating partners should be advised to use barrier method contraception to prevent exposure to the foetus or neonate.
• •15. Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical study.