Additional identifiers
EudraCT number
2016-005228-27
ClinicalTrials.gov number
Protocol/serial number
33584
Study information
Scientific title
INTERIM: a randomised phase II feasibility study of INTERmittent versus continuous dosing of oral targeted combination therapy In patients with BRAFV600 mutant stage 3 unresectable or metastatic Melanoma
Acronym
INTERIM
Study hypothesis
This feasibility study aims to determine if intermittent dosing is deliverable, based on patient and professional willingness to take part in a randomised trial evaluating less rather than standard durations of treatment. The trial will evaluate treatment compliance, Progression Free Survival and Quality of Life, to inform whether a subsequent definitive trial is justified and how it should be designed.
Ethics approval
Cambridge South Research Ethics Committee, ref: 17/EE/0340
Study design
Randomised; Interventional; Design type: Treatment, Drug, Imaging
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Specialty: Cancer, Primary sub-specialty: Skin Cancer; UKCRC code/ Disease: Cancer/ Melanoma and other malignant neoplasms of skin
Intervention
All participants receive standard Dabrafenib+Trametinib, either taken continuously every day (continuous arm), or with planned treatment breaks in each 28 day cycle (intermittent arm).
Eligible patients are randomly assigned to either the continuous arm or the intermittent arm in a 1:1 ratio using the minimisation with random element method.
1. Stratification parameters are:
2. Eastern Cooperative Oncology Group (ECOG) performance status
3. Disease stage
4. Presence or absence of brain metastases
5. Lactate Dehydrogenase (LDH) levels
Patients will continue on allocated treatment as long as they benefit from the treatment and it is tolerable.
Follow-up for survival will be a minimum of 9 months to a maximum of 5 years from date of randomisation of the last patient.
Intervention type
Other
Phase
Phase II
Drug names
Primary outcome measure
1. Recruitment rate will be measured as the average number of patients recruited per site per two months. To be assessed once the trial has been recruiting for 15 months, or when 15 sites have been open for 6 months whichever is sooner
2. Treatment compliance is the percentage of patients completing the allocated treatment at 6 months from randomisation
3. Overall Quality of Life, defined as the global health status score derived from European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire at 6 months from randomisation
4. Progression Free Survival (assessed according to standard Response Criteria In Solid Tumours (RECIST v1.1), calculated as the duration from the date of randomisation to the date of first progression or death from any cause, which ever occurs first
Secondary outcome measures
1. Safety is assessed using the standard cancer National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V4.03 criteria thoughout the trial
2. Objective Response Rate will be assessed according to RECIST v1.1
T3. ime to treatment failure will be the time from starting drug treatment on day 1 of cycle 1 until the date of day 1 of the last cycle +28 days
3. Overall survival will be calculated as the duration from the date of randomisation to the date of death from any cause
4. Patient Reported outcomes focussing on skin toxicity evaluation will be assessed using skin-specific patient reported oucome measures throughout the trial
5. Patient experience will be assessed by a survey of patients in each arm of the trial, 9 months from randomisation. Also, semi-structured interviews in a subset of patients who have volunteered at a later time point
6. Quality of Life and Health Economics Evaluation using the EORTC QLQ-C30 and EQ5D questionnaires throughout the trial
Overall trial start date
23/01/2017
Overall trial end date
23/03/2020
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Signed informed consent
2. Age ≥18 years old
3. Histologically or cytologically confirmed BRAFV600 mutant stage 3 unresectable or metastatic melanoma
4. Measurable disease by RECIST
5. ECOG performance status 0-2
6. Minimum life expectancy 12 weeks
7. Adequate bone marrow, renal and liver function
8. Received no prior BRAF or MEK inhibitor therapy for metastatic disease
9. Willing and able to comply with the scheduled visits, treatment plans, laboratory tests, completion of QoL
questionnaires and other study procedures
10. Archival tumour tissue sample available
11. Women of child-bearing potential and all sexually active male patients must agree to use effective contraception methods throughout treatment
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 150; UK Sample Size: 150
Participant exclusion criteria
1. Concomitant immunotherapy being administered to treat advanced melanoma
2. Other invasive malignancies diagnosed within the last year which are not in complete remission, or for which additional therapy is required
3. 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
4. Women who are pregnant, plan to become pregnant or are lactating during the trial period
5. Other investigational anti-cancer drugs
6. Use of strong inducers and inhibitors of CYP3A or CYP2C8
Recruitment start date
23/10/2017
Recruitment end date
23/04/2019
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Addenbrookes Hospital
Oncology Centre
Box 193
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Trial participating centre
Churchill Hospital
Oxford Cancer Centre
Headington
Oxford
OX3 7LE
United Kingdom
Trial participating centre
The Christie Hospital
Wilmslow Road
Manchester
M20 4BX
United Kingdom
Trial participating centre
The Royal Marsden
Fulham Road
London / Downs Road
Sutton
SM2 5PT
United Kingdom
Trial participating centre
Norfolk & Norwich University Hospital
Colney Lane
Norwich
NR4 7UY
United Kingdom
Trial participating centre
Royal Preston Hospital
Sharoe Green Lane
Fulwood
Preston
PR2 9HT
United Kingdom
Trial participating centre
Charing Cross Hospital
Imperial College Healthcare NHS Trust
Fulham Place Road
London
W6 8RF
United Kingdom
Trial participating centre
University Hospital Birmingham (Queen Elizabeth)
Heritage Building
Mindelsohn Way
Edgebaston
Birmingham
B15 2TH
United Kingdom
Trial participating centre
Beatson West of Scotland Cancer Centre
1053 Great Weston Road
Glasgow
G12 OYN
United Kingdom
Trial participating centre
Edinburgh Cancer Centre
Western General Hospital
Crewe Road South
Edinburgh
EH4 2XU
United Kingdom
Trial participating centre
University College London Hospital
250 Euston Road
London
NW1 2PG
United Kingdom
Trial participating centre
Weston Park Hospital
Whitham Road
Sheffield
S10 2SJ
United Kingdom
Trial participating centre
Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
Trial participating centre
University Hospital Southampton
Medical Oncology
MP307 Level D East Wing
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
Trial participating centre
Bristol University Hospitals
Bristol Haematology and Oncology Centre
Horfield Road
Bristol
BS2 8ED
United Kingdom
Trial participating centre
Royal Free Hospital
Academic Oncology
Upper 4th Floor
Room U4/10,
Pond Street
London
NW3 2QG
United Kingdom
Funders
Funder type
Government
Funder name
National Institute for Health Research
Alternative name(s)
NIHR
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
It is planned that the main trial results will be presented at national and international conferences and published in peer –reviewed journal, within a year of the overall trial end date.
IPD sharing statement:
This is a feasibility study, the data sharing plans for this study are unknown and will be made at a later date.
Intention to publish date
23/03/2021
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list