Condition category
Cancer
Date applied
04/09/2017
Date assigned
14/09/2017
Last edited
14/09/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Lay summary under review with external organisation

Trial website

Contact information

Type

Public

Primary contact

Mrs Claire Mather

ORCID ID

Contact details

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

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

Not specified

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 measures

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

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

Sponsor information

Organisation

Cambridge University Hospitals NHS Foundation Trust

Sponsor details

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Sponsor type

Hospital/treatment centre

Website

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes