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 |
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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
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
Contact information
Scientific
Weston Park Hospital
Sheffield
S10 2SJ
United Kingdom
Phone | 0114 226 5000 |
---|---|
r.j.young@sheffield.ac.uk |
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
0000-0003-0599-0245 | |
Phone | +44 (0)121 415 8421 |
j.savage.1@bham.ac.uk |
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 |
---|---|
scart@contacts.bham.ac.uk |
Study information
Study design | Non-randomized interventional study |
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Primary study design | Interventional |
Secondary study design | Non randomised study |
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 | Phase 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 acronym | SCART |
Study objectives | Cancer 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) studied | Sarcoma |
Intervention | Selumetinib, 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 type | Drug |
Pharmaceutical study type(s) | |
Phase | Phase I/II |
Drug / device / biological / vaccine name(s) | Selumetinib |
Primary outcome measure | Objective response rates; Timepoint(s): Phase I and II |
Secondary outcome measures | 1. 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 date | 12/03/2012 |
Completion date | 31/01/2018 |
Reason abandoned (if study stopped) | Participant recruitment issue |
Eligibility
Participant type(s) | Patient |
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Age group | Adult |
Lower age limit | 18 Years |
Sex | Both |
Target number of participants | Planned Sample Size: 37; UK Sample Size: 37 |
Total final enrolment | 19 |
Key inclusion criteria | 1. 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 criteria | 1. 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 enrolment | 12/03/2012 |
Date of final enrolment | 31/12/2016 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
Study participating centres
Sheffields
S10 2SJ
United Kingdom
London
NW3 2QG
United Kingdom
Brighton
BN2 5BE
United Kingdom
London
SW10 9NH
United Kingdom
Glasgow
G12 0YN
United Kingdom
Manchester
M20 4BX
United Kingdom
Sponsor information
Hospital/treatment centre
Research Department
11 Broomfield Road
Sheffield
S10 2SE
England
United Kingdom
https://ror.org/018hjpz25 |
Funders
Funder type
Charity
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 date | 01/06/2023 |
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Individual participant data (IPD) Intention to share | Yes |
IPD sharing plan summary | Available on request |
Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
IPD sharing plan | Current 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
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