Study of oral MEK inhibitor selumetinib (AZD6244 hyd-sulphate) in combination with highly active anti retroviral therapy (HAART) in AIDS-associated Kaposi's sarcoma (KS)

ISRCTN ISRCTN24921472
DOI https://doi.org/10.1186/ISRCTN24921472
EudraCT/CTIS number 2011-003099-35
ClinicalTrials.gov number NCT01752569
Secondary identifying numbers 11876
Submission date
02/03/2012
Registration date
02/03/2012
Last edited
23/05/2025
Recruitment status
Stopped
Overall study status
Stopped
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Current plain English summary as of 13/02/2019:
https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-selumetinib-people-kaposis-sarcoma-scart

Previous plain English summary:
http://cancerhelp.cancerresearchuk.org/trials/a-trial-looking-selumetinib-people-kaposis-sarcoma-scart

Study website

Contact information

Dr Robin Young
Scientific

Weston Park Hospital
Sheffield
S10 2SJ
United Kingdom

Phone 0114 226 5000
Email r.j.young@sheffield.ac.uk
Dr Joshua Savage
Scientific

Early Drug Development Team Leader
Cancer Research UK Clinical Trials Unit (CRCTU)
Institute of Cancer and Genomic Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

ORCiD logoORCID ID 0000-0003-0599-0245
Phone +44 (0)121 415 8421
Email j.savage.1@bham.ac.uk
Dr SCART Team
Public

Cancer Research UK Clinical Trials Unit (CRCTU)
Institute of Cancer and Genomic Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Phone +44 (0) 121 414 6754
Email scart@contacts.bham.ac.uk

Study information

Study designNon-randomized interventional study
Primary study designInterventional
Secondary study designNon randomised study
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titlePhase I/II study of oral MEK inhibitor selumetinib (AZD6244 hyd-sulphate) in combination with highly active anti retroviral therapy (HAART) in AIDS-associated Kaposi's sarcoma (KS)
Study acronymSCART
Study objectivesCancer is a leading cause of death in individuals living with HIV, and Kaposi's sarcoma (KS) remains the commonest HIV-associated cancer. KS results from co-infection with HIV and another virus, HHV-8. Laboratory studies have shown that HHV-8 viral proteins stimulate intracellular signalling pathways within KS lesions which promotes their growth. Selumetinib targets these signalling pathways and may therefore be a useful new therapy for KS.

SCART is a national multi-centre study. The objectives of the SCART trial are to determine a safe and tolerable dose for selumetinib in combination with HIV anti-retroviral therapy, and to determine whether selumetinib reduces KS lesions in HIV positive patients.

More details can be found at http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=11876 (link no longer works as of 13/02/2019)
Ethics approval(s)Approved 10/11/2011, Yorkshire and the Humber - Leeds East (NHSBT Newcastle Blood Donor Centre
Holland Drive, Newcastle upon Tyne, NE2 4NQ, UK; +44 (0)207 1048171, (0)207 104 8141; leedseast.rec@hra.nhs.uk), ref: 11/YH/0373
Health condition(s) or problem(s) studiedSarcoma
InterventionSelumetinib, Orally bioavailable, selective inhibitor of MEK 1/2, inhibiting the phosphorylation of ERK 1/2

Patients will undergo 6 x 21-day (3-weekly) cycles of treatment. There is a screening visit following by visits every at the end of every cycle. In Phase I during cycle 1 there are weekly visits. Visits involve clinical examination, periodic clinical photographs of lesions, haematology/biochemistry, blood samples taken for translational studies. CT, ECHO or Multi Gated Acquisition Scan (MUGA). Ophthalmologic exam will occur during screening. Further assessments of this nature will only be performed if judged clinically necessary. Patients will have a follow-up visit every 12 weeks for 12 months to record changes in lesions by clinical photographs.
Intervention typeDrug
Pharmaceutical study type(s)
PhasePhase I/II
Drug / device / biological / vaccine name(s)Selumetinib
Primary outcome measureObjective response rates; Timepoint(s): Phase I and II
Secondary outcome measures1. HAART Drug Levels; Timepoint(s): Phase I
2. HIV control; Timepoint(s): Phase I and II
3. Number of selumetinib cycles completed; Timepoint(s): Phase I and II
4. PBMC Sub-study; Timepoint(s): Phase I and II; PD measures of selumetinib in combination with HAART; Timepoint(s): Phase I and II
5. Progression free survival rate; Timepoint(s): Phase I and II - 6 months post ccompletion of study
6. Selumetinib and metabolite serum levels; Timepoint(s): phase I
7. Toxicity; Timepoint(s): Phase I and II
Overall study start date12/03/2012
Completion date31/01/2018
Reason abandoned (if study stopped)Participant recruitment issue

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participantsPlanned Sample Size: 37; UK Sample Size: 37
Total final enrolment19
Key inclusion criteria1. Human immunodeficiency virus (HIV) positive and established on a HAART regimen for >=3 months
2. Histologically confirmed KS
3. Measurable disease according to AIDS Clinical Trials Group (ACTG) criteria
4. Evidence of disease progression in the past 6 months, without anticancer treatment since progression
5. Progressive cutaneous or nodal KS not requiring chemotherapy or progressive KS following cytotoxic chemotherapy
6. Adequate haematological function:
6.1. Haemoglobin = 9 g/dL
6.2. Absolute neutrophil count = 1.5 x 10 9/L
6.3. Platelets = 100 x 10 9/L
7. Adequate hepatic function:
7.1. Serum bilirubin = 1.5 x upper limit of normal (ULN)
7.2. Alanine aminotransferase (ALT) = 2.5 x ULN
7.3. Aspartate aminotransferase (AST) = 2.5 x ULN
8. Adequate renal function:
8.1. Serum creatinine clearance > 50 ml/min (Cockcroft-Gault formula or 24 hour urine collection)
8.2. Left ventricular function >50% normal
9. Age = 18 years.
10. Eastern Cooperative Oncology Group (ECOG) performance status > 2
11. For selumetinib, women of child bearing age and child bearing potential must have a negative pregnancy test prior to study entry and be using an adequate contraception method, which must be continued while on treatment and for at least 4 weeks after the study treatment has ended
12. Male patients must agree to use an effective contraception method while on treatment and for at least 16 weeks after the study treatment has ended (barrier contraception is recommended for all individuals living with HIV).
13. Written informed consent
Key exclusion criteria1. HIV viral load > 200 copies/ml
2. Any previous treatment with a Ras, Raf or MEK inhibitor
3. Active opportunistic infections.
4. Known hepatitis B, hepatitis C
5. Clinical evidence of uncontrolled hypertension (systolic BP > 150 mmHg or diastolic BP > 90 mmHg on 2 readings = 1 hour apart))
6. Clinical evidence of heart failure (= New York Heart Association [NYHA] Class II)
7. Clinical evidence of atrial fibrillation (heart rate > 100 bpm) or unstable ischaemic heart disease (MI within 6 months prior to starting treatment or angina requiring the use of nitrates > once weekly)
8. Major surgery within 4 weeks prior to starting selumetinib
9. Evidence of any psychological, familial, sociological or geographical condition potentially hampering protocol compliance
10. Clinical judgement by the Investigator that the patient should not participate in the study
11. Refractory nausea, vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease) or significant bowel resection that would preclude adequate absorption
12. Treatment with any investigational product within 28 days of registration
13. Pregnant or breastfeeding women
Date of first enrolment12/03/2012
Date of final enrolment31/12/2016

Locations

Countries of recruitment

  • England
  • Scotland
  • United Kingdom

Study participating centres

Weston Park Hospital
Whitham Road
Sheffields
S10 2SJ
United Kingdom
Royal Free London NHS Foundation Trust Royal Free Hospital
Pond Street
London
NW3 2QG
United Kingdom
Royal Sussex County Hospital
Eastern Road
Brighton
BN2 5BE
United Kingdom
Chelsea and Westminster NHS Foundation Trust
369 Fulham Road
London
SW10 9NH
United Kingdom
Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom
Christie Hospital
Wilmslow Road
Manchester
M20 4BX
United Kingdom

Sponsor information

Sheffield Teaching Hospitals NHS Trust (UK)
Hospital/treatment centre

Research Department
11 Broomfield Road
Sheffield
S10 2SE
England
United Kingdom

ROR logo "ROR" https://ror.org/018hjpz25

Funders

Funder type

Charity

Cancer Research UK (CRUK) (UK)
Private sector organisation / Other non-profit organizations
Alternative name(s)
CR_UK, Cancer Research UK - London, CRUK
Location
United Kingdom

Results and Publications

Intention to publish date01/06/2023
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
Publication and dissemination planPlanned publication in a high-impact peer-reviewed journal
IPD sharing planCurrent IPD sharing statement as of 01/02/2023:
The datasets generated during and/or analysed during the current study are/will be available upon request. Scientifically sound proposals from appropriately qualified researchers will be considered for data sharing. Requests should be made by returning a Data Sharing Request Form to newbusiness@trials.bham.ac.uk; this captures the research requirements, statistical analysis plan, and intended publication schedule. Requests will be reviewed by the Cancer Research UK Clinical Trials Unit (CRCTU) Directors in discussion with the Chief Investigator (CI), Trial Management Group (TMG), independent Data Monitoring Committee (DMC) and Sponsor (Sheffield Teaching Hospitals NHS Foundation Trust). They will consider the scientific validity of the request, qualifications of the researchers, CI, TMG & TSC views, consent arrangements, the practicality of anonymizing the requested data and contractual obligations. If supportive of the request, and where not already obtained, Sponsor consent for data transfer will be sought before notifying applicants of the outcome. It is anticipated that applicants will be notified within 3 months of receipt of the original request.


Previous IPD sharing statement:
The data-sharing plans for the current study are unknown and will be made available at a later date

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Basic results version 1.0a 16/02/2023 16/02/2023 No No
HRA research summary 28/06/2023 No No
Results article 19/03/2025 25/03/2025 Yes No
Plain English results 23/05/2025 No Yes

Additional files

ISRCTN24921472_BasicResults_v1.0a_16Feb2023.pdf

Editorial Notes

23/05/2025: A link to plain English results was added.
25/03/2025: Publication reference added.
LH 16/02/2023: The basic results uploaded to the trial outputs table were replaced with v1.0a.
01/02/2023: The following changes were made:
1. The publication and dissemination plan and intention to publish date were added.
2. The Individual participant data (IPD) sharing statement and summary were changed.
3. Scientific contact added.
4. Website link added.
25/01/2023: The basic results have been uploaded to the trial outputs table and total final enrolment was added.
28/06/2019: ClinicalTrials.gov stated that this trial was terminated by February 2019 due to low recruitment.
13/02/2019: The following changes were made:
1. A public contact was added
2. The plain English summary was changed
3. The hypothesis was updated
4. Trial participating centres were added (Weston Park Hospital, Royal Sussex County Hospital, Chelsea and Westminster NHS Foundation Trust, Beatson West of Scotland Cancer Centre, Christie Hospital)
10/10/2016: Verified study status. Changed overall end date from 22/02/2013 to 31/01/2018. Changed recruitment end date from 22/02/2013 to 31/12/2016.
30/09/2016: No publications found, verifying study status with principal investigator