BRAFV600 mutant stage 3 unresectable or metastatic melanoma
Conditions
Interventions
Trade Name: dabrafenib
Product Name: dabrafenib
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: dabrafenib
CAS Number: 1195765-4
Sponsors
Cambridge University Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Signed informed consent • Age =18 years old • Histologically or cytologically confirmed BRAFV600 mutant stage 3 unresectable or metastatic melanoma • Measurable disease by RECIST • ECOG performance status 0-2 • Minimum life expectancy 12 weeks • Adequate bone marrow, renal and liver function • Received no prior BRAF or MEK inhibitor therapy for metastatic disease • Willing and able to comply with the scheduled visits, treatment plans, laboratory tests, completion of QoL questionnaires and other study procedures • Archival tumour tissue sample available • Women of child-bearing potential and all sexually active male patients must agree to use effective contraception methods throughout treatment Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: • Concomitant immunotherapy being administered to treat advanced melanoma • Other invasive malignancies diagnosed within the last year which are not in complete remission, or for which additional therapy is required • Significant acute or chronic medical or psychiatric condition, disease or laboratory abnormality which in the judgment of the investigator would place the patient at undue risk or interfere with the trial • Women who are pregnant, plan to become pregnant or are lactating during the trial period • Other investigational anti-cancer drugs • Use of strong inducers and inhibitors of CYP3A or CYP2C8
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess recruitment rate and treatment compliance of the intermittent dosing schedule as a measure of acceptance of intermittent dosing to patients and physicians • To evaluate the impact on overall QoL with intermittent dosing using European Organisation for Research and Treatment of Cancer (EORTC)QLQ-C30 • To estimate the size of clinical efficacy of intermittent dosing over continuous dosing, measured by PFS ; Secondary Objective: Secondary objectives • To evaluate safety, objective response rate, time to treatment failure and overall survival • To evaluate skin toxicity as assessed by clinicians and patients using patient reported outcome measures (Skindex-16 and patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)) • To assess factors which influence patients’ decision to enter/decline entering the trial • To assess patient experience of participation in this trial (using mixed methods) • To determine the QoL and cost-effectiveness of intermittent dosing compared with standard continuous dosing Exploratory Objectives • To explore emergence of resistance by means of ctDNA collected from patients during the course of their treatment • To determine the role of ctDNA as a useful biomarker for therapeutic monitoring • In a subset of patients (up to 20), explore pharmacokinetics of standard versus intermittent dosing schedules ; Primary end point(s): • Recruitment rate will be measured as the average number of patients recruited per site per 2 months • Treatment compliance is defined as the percentage of patients completing the allocated treatment at 6 months from the date of randomisation. Although the primary aim is to assess the compliance of the inter | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Safety is assessed using the standard cancer National Cancer institute (NCI) CTCAE v4.03 criteria • Objective Response Rate is assessed according to RECIST v1.1 (Appendix 1) • Time to treatment failure is the time from starting drug treatment with dabrafenib+trametinib on day 1 of cycle 1 until the date of day 1 of the last cycle +28 days; if a patient receives any other anti-cancer treatment including surgery they will be censored at the date of last treatment prior to this • Overall survival is calculated as the duration from the date of randomisation to the date of death from any cause • Objective Response Rate is assessed according to RECIST v1.1 (Appendix 1) • Patient reported outcomes focussing on skin toxicity evaluation is assessed using skin-specific patient reported outcome measures (PROM) – the Skindex-16 and NCI PRO-CTCAE items • Patient experience is assessed by a) patient experience survey of patients in each arm of the trial and b) semi-structured interviews of patient volunteers • QoL & Health Economic Evaluation: the EORTC QLQ-C30 and EQ5D generic measure of health status which will be used for the cost-effectiveness analysis. ; Timepoint(s) of evaluation of this end point: • Safety evaluated throughout trial • Objective Response Rate evaluated throughout trial • Time to treatment failure evaluated throughout trial • Overall survival evaluated throughout trial • Patient reported outcomes evaluated throughout trial • Patient experience evaluated 9 months from randomisation • QoL & Health Economic Evaluation evaluated throughout trial | — |
Countries
United Kingdom
Contacts
Public ContactMrs Carrie Bayliss
CCTU
Outcome results
None listed