Clinical Trials /

A Phase I, First in Man Study to Evaluate the Safety and Tolerability of a panRAF Inhibitor (CCT3833/BAL3833)in Patients With Solid Tumours



The study is a first in man, dose escalation study to evaluate the safety, tolerability and how the drug works in the body in patients with all solid tumours. The aim of this study is to determine the most effective dose of the study drug that can then be further investigated in patients with advanced melanoma.

Related Conditions:
  • Malignant Solid Tumor
  • Melanoma
Recruiting Status:



Phase 1

Trial Eligibility



  • Brief Title: A Phase I, First in Man Study to Evaluate the Safety and Tolerability of a panRAF Inhibitor (CCT3833/BAL3833)in Patients With Solid Tumours
  • Official Title: A Phase 1, First in Man, Dual Centre, Open-label Dose Escalation Study With Expansion to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CCT3833 (BAL3833), a panRAF Inhibitor, Given Orally in Patients With Advanced Solid Tumours, Including Metastatic Melanoma

Clinical Trial IDs

  • ORG STUDY ID: 4232
  • NCT ID: NCT02437227


  • Melanoma
  • Cancer


CCT3833Experimental: CCT3833


The study is a first in man, dose escalation study to evaluate the safety, tolerability and how the drug works in the body in patients with all solid tumours. The aim of this study is to determine the most effective dose of the study drug that can then be further investigated in patients with advanced melanoma.

Detailed Description

      Metastatic malignant melanoma is the 5th most common cancer in the UK, with a notable
      proportion of young patients. The development of immunotherapies (such as Ipilimumab), and
      targeted therapies (such as Vemurafenib, a BRAF inhibitor) have resulted in improved survival
      outcomes for patients but is still only measured in months and not years. These targeted
      therapies are also only useful for patients with the relevant genetic mutation, leaving a
      significant proportion of patients without targeted therapy options. The need for more
      effective (and ideally curative) melanoma treatments remains. The Institute of Cancer
      Research, with funding from the Wellcome Trust, have created and developed a new panel of
      inhibitors that aim to more effectively terminate the growth, spread and survival signals
      that sustain the cancer. The broader targets allow patients possessing a range of genetic
      mutations to potentially benefit from this targeted therapy. It is hoped that these drugs
      could be used as both primary therapy for treatmentnaive patients as well as rescue therapy
      for those who have progressed on other targeted therapies.

      This is a phase 1 study to evaluate the safety and effectiveness of one of these new
      compounds, CCT 3833, and to define the maximum tolerated dose in patients with advanced
      melanoma. The study also aims to examine the way that CCT3833 works within the body. Once the
      maximum tolerated dose has been established a small number of melanoma patients, with
      specific mutations and at different treatment option stages, will be treated to gain
      additional safety information and an initial indication of the possible efficacy of CCT3833
      on melanoma tumours.

Trial Arms

Experimental: CCT3833ExperimentalThe starting dose of CCT3833 is 20 mg, taken as two 10 mg capsules. The starting schedule is a once daily continuous dosing schedule, but other dosing regimens may be considered depending on tolerability and exposures.The first dose of continuous dosing defines Cycle 1 Day 1. All treatment cycles have a duration of 28 days.
  • CCT3833

Eligibility Criteria

        Inclusion Criteria:

          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)

        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.

               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
             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

               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.
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Establishing the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of CCT3833.
Time Frame:18 months
Safety Issue:
Description:The maximum tolerated dose is the dose at which no more than one patient out of up to six patients at the same dose level experience a highly probably or probably drug-related DLT as defined in the protocol. This dose level will be selected as the RP2D.

Secondary Outcome Measures

Measure:To determine the pharmacokinetic profile of CCT3833 in humans. (plasma levels of CCT3833)
Time Frame:18 months
Safety Issue:
Description:Assessment of plasma levels of CCT3833 for 48 hours between Days -7 to -3 before Cycle 1, and on Cycle 2, Day 1.
Measure:To explore possible anti-tumour activity of CCT3833 in patients with advanced solid tumours.(measurable response (clinical or radiological) in any of the patients, as determined by the RECIST criteria v1.1)
Time Frame:18 months
Safety Issue:
Description:Any measurable response (clinical or radiological) in any of the patients, as determined by the RECIST criteria v1.1.
Measure:Determining the correlation between PK exposures and tolerability and/or efficacy (i.e. defining the safe therapeutic range).
Time Frame:18 months
Safety Issue:
Description:Correlation of plasma levels of CCT3833 with markers of efficacy and adverse event reports.


Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Royal Marsden NHS Foundation Trust

Last Updated

June 12, 2019