Condition category
Cancer
Date applied
02/03/2012
Date assigned
02/03/2012
Last edited
10/10/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Dr Laura Crack

ORCID ID

Contact details

Cancer Research UK Clinical Trials Unit
Institute for Cancer Studies
Edgbaston
Birmingham
B15 2TT
United Kingdom
-
l.r.crack@bham.ac.uk

Additional identifiers

EudraCT number

2011-003099-35

ClinicalTrials.gov number

NCT01752569

Protocol/serial number

11876

Study information

Scientific title

Phase I/II study of oral MEK inhibitor Selumetinib (AZD6244 Hyd-Sulphate) in Combination with highly active AntiRetroviral Therapy (HAART) in AIDS-associated Kaposi’s sarcoma (KS)

Acronym

SCART

Study hypothesis

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

Ethics approval

Yorkshire and the Humber – Leeds East, 10/11/2011, ref: 11/YH/0373

Study design

Non-randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Topic: National Cancer Research Network, Infection; Subtopic: Sarcoma, Infection (all Subtopics); Disease: Soft Tissue, Infectious diseases and microbiology

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

Phase

Phase I/II

Drug names

Selumetinib

Primary outcome measures

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 trial start date

12/03/2012

Overall trial end date

31/01/2018

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 37; UK Sample Size: 37

Participant 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

Recruitment start date

12/03/2012

Recruitment end date

31/12/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Cancer Research UK Clinical Trials Unit
Birmingham
B15 2TT
United Kingdom

Trial participating centre

Royal Free London NHS Foundation Trust Royal Free Hospital
Pond Street
London
NW3 2QG
United Kingdom

Sponsor information

Organisation

Sheffield Teaching Hospitals NHS Trust (UK)

Sponsor details

Research Department
11 Broomfield Road
Sheffield
S10 2SE
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Cancer Research UK (CRUK) (UK)

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

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