Plain English Summary
Trial website
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 Kaposis 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 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 trial start date
12/03/2012
Overall trial end date
31/01/2018
Reason abandoned (if study stopped)
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
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
Basic results (scientific)
Publication list