A research study to compare treatment with dabrafenib and trametinib, either taken continuously every day, or intermittently (with planned treatment breaks in each cycle), in patients with metastatic Melanoma

ISRCTN	ISRCTN18183156
DOI	https://doi.org/10.1186/ISRCTN18183156
Clinical Trials Information System (CTIS)	2016-005228-27
Protocol serial number	33584
Sponsor	Cambridge University Hospitals NHS Foundation Trust
Funder	National Institute for Health Research

Submission date: 04/09/2017
Registration date: 14/09/2017
Last edited: 16/06/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-comparing-2-ways-of-giving-dabrafenib-and-trametinib-for-advanced-melanoma-interim

Contact information

Mrs Claire Mather
Public

INTERIM Trial Co-ordinator
Cambridge Clinical Trials Unit – Cancer Theme (CCTU-CT)
S4, Box 279
Addenbrooke’s Hospital
Cambridge
CB2 0QQ
United Kingdom

Ms Emily Foster
Scientific

Addenbrookes Hospital
Cambridge
CB2 0QQ
United Kingdom

Email	emily.foster@addenbrookes.nhs.uk

Study information

Primary study design	Interventional
Study design	Randomised; Interventional; Design type: Treatment, Drug, Imaging
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
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
Study acronym	INTERIM
Study objectives	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(s)	Cambridge South Research Ethics Committee, ref: 17/EE/0340
Health condition(s) or problem(s) studied	Melanoma
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
Primary outcome measure(s)	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
Key secondary outcome measure(s)	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
Completion date	27/11/2020

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	150
Total final enrolment	79
Key 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
Key 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
Date of first enrolment	23/10/2017
Date of final enrolment	28/03/2020

Locations

Countries of recruitment

United Kingdom
England
Scotland

Study participating centres

Addenbrookes Hospital

Oncology Centre
Box 193
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Churchill Hospital

Oxford Cancer Centre
Headington
Oxford
OX3 7LE
United Kingdom

The Christie Hospital

Wilmslow Road
Manchester
M20 4BX
United Kingdom

The Royal Marsden

Fulham Road
London / Downs Road
Sutton
SM2 5PT
United Kingdom

Norfolk & Norwich University Hospital

Colney Lane
Norwich
NR4 7UY
United Kingdom

Royal Preston Hospital

Sharoe Green Lane
Fulwood
Preston
PR2 9HT
United Kingdom

Charing Cross Hospital

Imperial College Healthcare NHS Trust
Fulham Place Road
London
W6 8RF
United Kingdom

University Hospital Birmingham (Queen Elizabeth)

Heritage Building
Mindelsohn Way
Edgebaston
Birmingham
B15 2TH
United Kingdom

Beatson West of Scotland Cancer Centre

1053 Great Weston Road
Glasgow
G12 OYN
United Kingdom

Edinburgh Cancer Centre

Western General Hospital
Crewe Road South
Edinburgh
EH4 2XU
United Kingdom

University College London Hospital

250 Euston Road
London
NW1 2PG
United Kingdom

Weston Park Hospital

Whitham Road
Sheffield
S10 2SJ
United Kingdom

Nottingham City Hospital

Hucknall Road
Nottingham
NG5 1PB
United Kingdom

University Hospital Southampton

Medical Oncology
MP307 Level D East Wing
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Bristol University Hospitals

Bristol Haematology and Oncology Centre
Horfield Road
Bristol
BS2 8ED
United Kingdom

Royal Free Hospital

Academic Oncology
Upper 4th Floor
Room U4/10
Pond Street
London
NW3 2QG
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and analysed during the current study will be available upon request from the Cambridge Clinical Trials Unit - Cancer Theme (CCTU-CT) (cctu.cancer@addenbrookes.nhs.uk). Fully anonymised data linked only to relevant samples collected will be shared. Data will only be available following submission of the full end of trial report, initial publications of the data, and upon approval of the CCTU-CT and Sponsor.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results		13/12/2021	16/06/2022	No	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Protocol file	version 4.0	01/08/2019	14/10/2022	No	No
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Additional files

ISRCTN18183156_PROTOCOL_V4.0_01Aug19.pdf: Protocol file

Editorial Notes

16/06/2023: Cancer Help UK lay summary link added to plain English summary field.
14/10/2022: Protocol uploaded (not peer reviewed).
21/06/2022: The following changes were made to the trial record:
1. The intention to publish date was changed from 30/06/2022 to 26/11/2022.
2. The trial website was added.
16/06/2022: EU Clinical Trials Register results added.
21/12/2021: The following changes were made to the trial record:
1. The intention to publish date was changed from 27/11/2021 to 30/06/2022.
2. A scientific contact was added.
10/05/2021: The following changes were made to the trial record:
1. The intention to publish date was changed from 23/03/2021 to 27/11/2021.
2. Total final enrolment and IPD sharing statement added.
19/04/2021: The overall trial end date was changed from 28/03/2020 to 27/11/2020.
07/04/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 23/04/2019 to 28/03/2020.
2. The overall end date was changed from 23/03/2020 to 28/03/2020.
03/04/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Skin Cancer; UKCRC code/ Disease: Cancer/ Melanoma and other malignant neoplasms of skin" to "Melanoma" following a request from the NIHR.
16/01/2018: Cancer Help UK lay summary link added to plain English summary field.
26/10/2017: Internal review.