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).
- Histologically confirmed KS.
- Measurable disease according to ACTG criteria.
- Evidence of disease progression in the past 6 months, without anticancer treatment
- Progressive cutaneous or nodal KS not requiring chemotherapy OR progressive KS
following cytotoxic chemotherapy.
- Adequate haematological function:
- Haemoglobin ≥ 9 g/dL
- Absolute neutrophil count ≥ 1.5 x 10 9/L
- Platelets ≥ 100 x 10 9/L
- Adequate hepatic function:
- Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
- ALT ≤ 2.5 x ULN
- AST ≤ 2.5 x ULN
- Adequate renal function:
- Serum creatinine clearance > 50 ml/min (Cockcroft-Gault formula or 24 hour urine
- Left ventricular function >50% normal
- Age ≥ 18 years.
- ECOG performance status ≤ 2.
- 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.
- 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).
- Written informed consent
- HIV viral load > 200 copies/ml.
- Any previous treatment with a Ras, Raf or MEK inhibitor.
- Active opportunistic infections.
- Known hepatitis B, hepatitis C.
- Clinical evidence of uncontrolled hypertension (systolic BP > 150 mmHg or diastolic
BP > 90 mmHg on 2 readings ≥ 1 hour apart).
- Clinical evidence of heart failure (≥NYHA Class II).
- 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).
- Major surgery within 4 weeks prior to starting selumetinib.
- Evidence of any psychological, familial, sociological or geographical condition
potentially hampering protocol compliance.
- Clinical judgement by the Investigator that the patient should not participate in the
- Refractory nausea, vomiting, chronic gastrointestinal diseases (e.g. inflammatory
bowel disease) or significant bowel resection that would preclude adequate
- Treatment with any investigational product within 28 days of registration
- Pregnant or breast-feeding women.