MelanomaPhase 1PanRAFNCT02437227
Dose Escalation Study With Expansion to Evaluate Safety, Tolerability, Pharmacokinetics & Pharmacodynamics of CCT3833
A Phase 1 study testing CCT3833 in people with Melanoma and Cancer, run by Royal Marsden NHS Foundation Trust at 2 sites in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- What is being tested?
- CCT3833
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 15 Apr 2015to Jul 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years or over.
- Written (signed and dated) informed consent and willing and capable of co-operating with study procedures, treatment and follow-up.
- Histologically proven advanced or metastatic solid tumours.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy of at least 12 weeks.
- Haematological and biochemical indices (within 7 days before the first dose of CCT3833) within the ranges shown below:
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- Haemoglobin (Hb) ≥ 9.0 g/dL.
- Absolute neutrophil count ≥ 1.5 x 109/L.
- Platelet count ≥ 100 x 109/L.
- 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).
- Calculated creatinine clearance > 50 mL/min (based on Cockcroft-Gault calculation).
- Negative pregnancy test for females of child-bearing age.
- Patients must meet ALL of the above criteria and additionally meet the following criteria:
- Histologically proven locally advanced (unresectable) or metastatic melanoma.
- Documented presence of either BRAF or RAS mutations, as established by validated mutation testing from tumour biopsy.
- Evidence of measurable disease (according to RECIST v1.1)
Who cannot join
- 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:
- 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.)
- Major surgery within the last four weeks.
- 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:
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- High medical risk because of non-malignant systemic disease including active, uncontrolled infection.
- Known allergy to any pharmaceutical excipients.
- Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV). Testing for these viruses is not mandatory.
- Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- History or presence of ventricular tachyarrhythmia.
- 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.
- Repeated presence of a prolonged QTc interval > 450 ms at baseline (as calculated by Fridericia method).
- Unstable angina pectoris or acute myocardial infarction in the last 12 months prior to starting study drug.
- 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).
- Uncontrolled hypertension that remains uncontrolled on > 1 antihypertensive agent.
- 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.
- Inability to take oral medication; impairment of GI function or GI disease that could interfere with drug absorption.
- 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.
- Are taking warfarin as an oral anticoagulant; patients anticoagulated with low molecular weight heparin are not excluded from the trial.
- 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:
- Total abstinence.
- Male or female sterilization.
- A combination of any two of the following:
- 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.
- 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.
- Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical study.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Christie NHS Foundation Trust
Manchester, Greater Manchester, M20 4BX
Royal Marsden NHS Foundation Trust
Sutton, Surrey, SM2 5PT
About this study
Official title: A Phase 1, Dose Escalation Study With Expansion to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CCT3833 (BAL3833), a panRAF Inhibitor, in Patients With Advanced Solid Tumours, Including Metastatic Melanoma
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.
Read the 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.
- Being tested
- CCT3833
- Medical subject headings
- Melanoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CCT3833Drug
Also called panRAF inhibitor, given orally in patients with advanced solid tumours, including metastatic melanoma
CCT3833 is a poorly soluble crystalline compound. It is multi-polymorphic and one form, designated Form D, has been purified and typically has a particle size of about 15-20 μm. Form D readily absorbs and desorbs water, but is not a hydrate and has been selected as the form to take forward into clinical development.
| Study group | Role | What they receive |
|---|---|---|
| Experiment - CCT3833 Cohort 1 | Experimental | Part A - Dose escalation stage - Dose level 1 : 20mg Receives: Drug: CCT3833 |
| Experiment - CCT3833 Cohort 2 | Experimental | Part A - Dose escalation stage - Dose level 2 : 40mg Receives: Drug: CCT3833 |
| Experiment - CCT3833 Cohort 3 | Experimental | Part A - Dose escalation stage - Dose level 3 : 75mg Receives: Drug: CCT3833 |
| Experiment - CCT3833 Cohort 4 | Experimental | Part A - Dose escalation stage - Dose level 4 : 150mg Receives: Drug: CCT3833 |
| Experiment - CCT3833 Cohort 5 | Experimental | Part A - Dose escalation stage - Dose level 5:: 300mg Receives: Drug: CCT3833 |
| Experiment - CCT3833 Cohort 6 | Experimental | Part A - Dose escalation stage - Dose level 6 : 600mg Receives: Drug: CCT3833 |
| Experiment - CCT3833 Cohort 7 | Experimental | Part A - Dose escalation stage - Dose level 7 : 900mg Receives: Drug: CCT3833 |
| Experiment - CCT3833 Cohort 8 | Experimental | Part A - Dose escalation stage - Dose level 8 : 1350mg Receives: Drug: CCT3833 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and Percentage of Patients With Dose Limiting Toxicities (DLT).
Number of patients with DLT in each cohort/dose level. 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.
Measured: Patients were assessed for DLTs from trial treatment start (cycle 1 day 1) through each of the treatment (28 days) cycles until the patients' final safety follow up at 30 days after last dose for up to 18 months.
Assessing the Safety and Tolerability Profile of CCT3833. (Adverse Event)
Determining causality of each adverse event (AE) to CCT3833 and grade according to National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Measured: AEs were graded and recorded from the trial entry confirmation, at the treatment start cycle 1 day 1, at day 1 of each CCT3833 (28 days) cycles, until the patients' final safety follow up at 30 days after last dose for up to 18 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2015 (estimated)
- Study start15 Apr 2015
- Primary completionDec 2017
- Study completionJul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Dose escalation study with expansion. Each dose level constitutes a group/arm
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Marsden NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Institute of Cancer Research, United Kingdom, Wellcome Trust, Biomedical Research Centre for Cancer
- Responsible party
- Sponsor
- Investigators
- James Larkin, Dr, Principal investigator, Royla Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02437227
- Sponsor's protocol ID
- 4232
- Acronym
- PanRAF
- Status last verified
- Apr 2026
- First submitted
- 5 May 2015
- Last updated
- 12 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Dose Escalation Study With Expansion to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CCT3833 (BAL3833), a panRAF Inhibitor, in Patients With Advanced Solid Tumours, Including Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT02437227
- Acronym / sponsor ID
- PanRAF / 4232
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Royal Marsden NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Institute of Cancer Research, United Kingdom, Wellcome Trust, Biomedical Research Centre for Cancer
- Study start
- 15 Apr 2015 (actual)
- Primary completion
- Dec 2017 (actual)
- Study completion
- Jul 2018 (actual)
- First posted
- 7 May 2015 (estimated)
- Results
- Posted 12 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 8
- Model description
- Dose escalation study with expansion. Each dose level constitutes a group/arm
| Arm | Type | Receives |
|---|---|---|
| Experiment - CCT3833 Cohort 1 | Experimental | Drug: CCT3833Part A - Dose escalation stage - Dose level 1 : 20mg |
| Experiment - CCT3833 Cohort 2 | Experimental | Drug: CCT3833Part A - Dose escalation stage - Dose level 2 : 40mg |
| Experiment - CCT3833 Cohort 3 | Experimental | Drug: CCT3833Part A - Dose escalation stage - Dose level 3 : 75mg |
| Experiment - CCT3833 Cohort 4 | Experimental | Drug: CCT3833Part A - Dose escalation stage - Dose level 4 : 150mg |
| Experiment - CCT3833 Cohort 5 | Experimental | Drug: CCT3833Part A - Dose escalation stage - Dose level 5:: 300mg |
| Experiment - CCT3833 Cohort 6 | Experimental | Drug: CCT3833Part A - Dose escalation stage - Dose level 6 : 600mg |
| Experiment - CCT3833 Cohort 7 | Experimental | Drug: CCT3833Part A - Dose escalation stage - Dose level 7 : 900mg |
| Experiment - CCT3833 Cohort 8 | Experimental | Drug: CCT3833Part A - Dose escalation stage - Dose level 8 : 1350mg |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 18 years or over.
- Written (signed and dated) informed consent and willing and capable of co-operating with study procedures, treatment and follow-up.
- Histologically proven advanced or metastatic solid tumours.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy of at least 12 weeks.
Key exclusion criteria (27 listed)
- Patients who meet ANY of the following criteria will not be eligible to participate.
- 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.)
- Major surgery within the last four weeks.
- 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.
- High medical risk because of non-malignant systemic disease including active, uncontrolled infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CCT3833Also: panRAF inhibitor, given orally in patients with advanced solid tumours, including metastatic melanomaCCT3833 is a poorly soluble crystalline compound. It is multi-polymorphic and one form, designated Form D, has been purified and typically has a particle size of about 15-20 μm. Form D readily absorbs and desorbs water, but is not a hydrate and has been selected as the form to take forward into clinical development. | Drug | Experiment - CCT3833 Cohort 1, Experiment - CCT3833 Cohort 2, Experiment - CCT3833 Cohort 3, Experiment - CCT3833 Cohort 4, Experiment - CCT3833 Cohort 5, Experiment - CCT3833 Cohort 6, Experiment - CCT3833 Cohort 7, Experiment - CCT3833 Cohort 8 |
Primary outcome
Number and Percentage of Patients With Dose Limiting Toxicities (DLT).
Time frame: Patients were assessed for DLTs from trial treatment start (cycle 1 day 1) through each of the treatment (28 days) cycles until the patients' final safety follow up at 30 days after last dose for up to 18 months.
Number of patients with DLT in each cohort/dose level. 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.
Assessing the Safety and Tolerability Profile of CCT3833. (Adverse Event)
Time frame: AEs were graded and recorded from the trial entry confirmation, at the treatment start cycle 1 day 1, at day 1 of each CCT3833 (28 days) cycles, until the patients' final safety follow up at 30 days after last dose for up to 18 months.
Determining causality of each adverse event (AE) to CCT3833 and grade according to National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Larkin, Dr principal investigator
Royla Marsden NHS Foundation Trust
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CCT3833 in people with Melanoma and Cancer, run by Royal Marsden NHS Foundation Trust at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number and Percentage of Patients With Dose Limiting Toxicities (DLT). (time frame: Patients were assessed for DLTs from trial treatment start (cycle 1 day 1) through each of the treatment (28 days) cycles until the patients' final safety follow up at 30 days after last dose for up to 18 months.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2026; AzTrials last refreshed its copy on 1 Nov 2026.