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)
- Conditions
- SarcomaCancerKaposi's sarcoma
- Registration Number
- ISRCTN24921472
- Lead Sponsor
- Sheffield Teaching Hospitals NHS Trust (UK)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Stopped
- Sex
- All
- Target Recruitment
- 19
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Objective response rates; Timepoint(s): Phase I and II
- Secondary Outcome Measures
Name Time Method <br> 1. HAART Drug Levels; Timepoint(s): Phase I<br> 2. HIV control; Timepoint(s): Phase I and II<br> 3. Number of selumetinib cycles completed; Timepoint(s): Phase I and II<br> 4. PBMC Sub-study; Timepoint(s): Phase I and II; PD measures of selumetinib in combination with HAART; Timepoint(s): Phase I and II<br> 5. Progression free survival rate; Timepoint(s): Phase I and II - 6 months post ccompletion of study<br> 6. Selumetinib and metabolite serum levels; Timepoint(s): phase I<br> 7. Toxicity; Timepoint(s): Phase I and II<br>