1. 18 years or over.
2. Written (signed and dated) informed consent and willing and capable of co-operating
with study procedures, treatment and follow-up.
3. Histologically proven advanced or metastatic solid tumours.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Life expectancy of at least 12 weeks.
6. Haematological and biochemical indices (within 7 days before the first dose of
CCT3833) within the ranges shown below:
1. Haemoglobin (Hb) 9.0 g/dL.
2. Absolute neutrophil count 1.5 x 109/L.
3. Platelet count 100 x 109/L.
4. Total bilirubin 1.5 x upper limit of normal (ULN), and Alanine
aminotransferase (ALT) and aspartate aminotransferase (AST) 2.5 x (ULN) (or
5 x ULN if elevated due to tumour).
5. Calculated creatinine clearance > 50 mL/min (based on Cockcroft-Gault
7. Negative pregnancy test for females of child-bearing age.
Inclusion criteria: dose expansion cohort
Patients must meet ALL of the above criteria and additionally meet the following criteria:
1. Histologically proven locally advanced (unresectable) or metastatic melanoma.
2. Documented presence of either BRAF or RAS mutations, as established by validated
mutation testing from tumour biopsy.
3. Evidence of measurable disease (according to RECIST v1.1)
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,
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.
2. Presence of unstable atrial fibrillation (ventricular response > 100 bpm);
patients with stable atrial fibrillation are eligible, provided they do not meet
any of the other cardiac exclusion criteria.
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
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
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
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.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both