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

NCT02437227 | Completed Phase 1 DMC

• 1 other identifier: 4232
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Melanoma; Cancer

Outcome Measures

Primary Outcomes (2)

• Establishing the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of CCT3833.

  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.

  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 NCI CTCAE v4.03.

  18 months

Secondary Outcomes (3)

• To determine the pharmacokinetic profile of CCT3833 in humans. (plasma levels of CCT3833)

  18 months

• 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)

  18 months

• Determining the correlation between PK exposures and tolerability and/or efficacy (i.e. defining the safe therapeutic range).

  18 months

Other Outcomes (3)

• To investigate the pharmacodynamic profile of CCT3833 in humans and to establish a biologically-active dose range.

  18 months

• 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.

  18 months

• Obtaining plasma samples for potential metabolite characterisation.

  18 months

Study Arms (1)

Experimental: CCT3833

EXPERIMENTAL

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.

Drug: CCT3833

Interventions

CCT3833 DRUG

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.

Experimental: CCT3833

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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:
• 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.
• 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.

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• Institute of Cancer Research, United Kingdom: collaborator
• Wellcome Trust: collaborator
• Biomedical Research Centre for Cancer: collaborator

Study Sites (2)

Christie NHS Foundation Trust

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

Royal Marsden NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Melanoma; Neoplasms

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• James Larkin, Dr

  Royla Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2015
• First Posted: May 7, 2015
• Study Start: April 15, 2015
• Primary Completion: December 1, 2017
• Study Completion: July 1, 2018
• Last Updated: June 12, 2019

Record last verified: 2019-06

Locations

GB (2)