A Phase I, First in Man Study to Evaluate the Safety and Tolerability of a panRAF Inhibitor (CCT3833/BAL3833)in Patients With Solid Tumours (PanRAF)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02437227|
Recruitment Status : Completed
First Posted : May 7, 2015
Last Update Posted : June 12, 2019
|Condition or disease||Intervention/treatment||Phase|
|Melanoma Cancer||Drug: CCT3833||Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||31 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||April 15, 2015|
|Actual Primary Completion Date :||December 2017|
|Actual Study Completion Date :||July 2018|
Experimental: Experimental: CCT3833
The 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 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.
- Establishing the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of CCT3833. [ Time Frame: 18 months ]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.
- Assessing the safety and tolerability profile of CCT3833. (adverse event) [ Time Frame: 18 months ]Determining causality of each adverse event (AE) to CCT3833 and grade according to NCI CTCAE v4.03.
- To determine the pharmacokinetic profile of CCT3833 in humans. (plasma levels of CCT3833) [ Time Frame: 18 months ]Assessment of plasma levels of CCT3833 for 48 hours between Days -7 to -3 before Cycle 1, and on Cycle 2, Day 1.
- 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 ]Any measurable response (clinical or radiological) in any of the patients, as determined by the RECIST criteria v1.1.
- Determining the correlation between PK exposures and tolerability and/or efficacy (i.e. defining the safe therapeutic range). [ Time Frame: 18 months ]Correlation of plasma levels of CCT3833 with markers of efficacy and adverse event reports.
- To investigate the pharmacodynamic profile of CCT3833 in humans and to establish a biologically-active dose range. [ Time Frame: 18 months ]Correlation of plasma levels of CCT3833 against tumour shrinkage data from imaging.
- Determining magnitude and duration of effect in biomarkers (such as ERK, phosphorylated-ERK, Cyclin D1 and Ki-67) in surrogate and tumour tissue following CCT3833 administration. [ Time Frame: 18 months ]Evaluation of a range of biomarkers from biopsies and optional blood biomarkers taken at baseline, on-treatment, and at disease progression.
- Obtaining plasma samples for potential metabolite characterisation. [ Time Frame: 18 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02437227
|Christie NHS Foundation Trust|
|Manchester, Greater Manchester, United Kingdom, M20 4BX|
|Royal Marsden NHS Foundation Trust|
|Sutton, Surrey, United Kingdom, SM2 5PT|
|Principal Investigator:||James Larkin, Dr||Royla Marsden NHS Foundation Trust|