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 |
| EudraCT/CTIS number | 2016-005228-27 |
| Secondary identifying numbers | 33584 |
- 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
Contact information
Mrs Claire Mather
Public
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
Scientific
Addenbrookes Hospital
Cambridge
CB2 0QQ
United Kingdom
| emily.foster@addenbrookes.nhs.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment, Drug, Imaging |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient 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 | 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 study start date | 23/01/2017 |
| Completion date | 27/11/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 150; UK Sample Size: 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
- England
- Scotland
- United Kingdom
Study participating centres
Addenbrookes Hospital
Oncology Centre
Box 193
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Box 193
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Churchill Hospital
Oxford Cancer Centre
Headington
Oxford
OX3 7LE
United Kingdom
Headington
Oxford
OX3 7LE
United Kingdom
The Christie Hospital
Wilmslow Road
Manchester
M20 4BX
United Kingdom
Manchester
M20 4BX
United Kingdom
The Royal Marsden
Fulham Road
London / Downs Road
Sutton
SM2 5PT
United Kingdom
London / Downs Road
Sutton
SM2 5PT
United Kingdom
Norfolk & Norwich University Hospital
Colney Lane
Norwich
NR4 7UY
United Kingdom
Norwich
NR4 7UY
United Kingdom
Royal Preston Hospital
Sharoe Green Lane
Fulwood
Preston
PR2 9HT
United Kingdom
Fulwood
Preston
PR2 9HT
United Kingdom
Charing Cross Hospital
Imperial College Healthcare NHS Trust
Fulham Place Road
London
W6 8RF
United Kingdom
Fulham Place Road
London
W6 8RF
United Kingdom
University Hospital Birmingham (Queen Elizabeth)
Heritage Building
Mindelsohn Way
Edgebaston
Birmingham
B15 2TH
United Kingdom
Mindelsohn Way
Edgebaston
Birmingham
B15 2TH
United Kingdom
Beatson West of Scotland Cancer Centre
1053 Great Weston Road
Glasgow
G12 OYN
United Kingdom
Glasgow
G12 OYN
United Kingdom
Edinburgh Cancer Centre
Western General Hospital
Crewe Road South
Edinburgh
EH4 2XU
United Kingdom
Crewe Road South
Edinburgh
EH4 2XU
United Kingdom
University College London Hospital
250 Euston Road
London
NW1 2PG
United Kingdom
London
NW1 2PG
United Kingdom
Weston Park Hospital
Whitham Road
Sheffield
S10 2SJ
United Kingdom
Sheffield
S10 2SJ
United Kingdom
Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
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
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
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
Upper 4th Floor
Room U4/10
Pond Street
London
NW3 2QG
United Kingdom
Sponsor information
Cambridge University Hospitals NHS Foundation Trust
Hospital/treatment centre
Hospital/treatment centre
Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom
"ROR" |
https://ror.org/04v54gj93 |
|---|
Funders
Funder type
Government
National Institute for Health Research
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 26/11/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| 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 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 | |
| Protocol file | version 4.0 | 01/08/2019 | 14/10/2022 | No | No |
| HRA research summary | 28/06/2023 | No | No |
Additional files
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.
