A phase I/II trial of selumetinib in combination with anti-retroviral therapy for AIDS-associated Kaposi's sarcoma
- Conditions
- AIDS-associated Kaposi's sarcomaMedDRA version: 18.1 Level: PT Classification code 10023286 Term: Kaposi's sarcoma AIDS related System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-003099-35-GB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 37
•HIV positive and established on a HAART regimen for = 3 months.
•Histologically confirmed KS.
•Measurable disease according to ACTG criteria.
•Evidence of disease progression in the past 6 months.
•Progressive cutaneous or nodal KS not requiring chemotherapy OR progressive KS following cytotoxic chemotherapy.
•Adequate haematological function:
o Haemoglobin = 9 g/dL
o Absolute neutrophil count = 1.5 x 10 9/L
o Platelets = 100 x 10 9/L
•Adequate hepatic function:
o Serum bilirubin = 1.5 x upper limit of normal (ULN), except if the patient is established on the anti-retroviral drug atazanavir (no upper limit) and has AST and ALT levels = 2.5 x ULN
o ALT = 2.5 x ULN
o AST = 2.5 x ULN
•Adequate renal function:
o Serum creatinine clearance > 50 ml/min (Cockcroft-Gault formula or 24 hour urine collection).
•Left ventricular function >50% normal
•Age = 18 years.
•World Health Organisation (WHO0 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
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0
•HIV viral load > 200 copies/ml.
•Active opportunistic infections.
•Active hepatitis B, hepatitis C.
Any prior exposure to MEK, Ras, or Raf inhibitors or history of hypersensitivity to selumetinib, or any excipient agents.
• Any unresolved toxicity > CTCAE Grade 2 from previous anti-cancer therapy, except for alopecia
• Cardiac conditions as follows:
o Uncontrolled hypertension (BP =150/95 mmHg despite medical therapy)
o Left ventricular ejection fraction <55% measured by echocardiography
o Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest
o Symptomatic heart failure (NYHA grade II-IV)
o Prior or current cardiomyopathy
o Severe valvular heart disease
o Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy)
o Acute coronary syndrome within 6 months prior to starting treatment
•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 study.
•Refractory nausea, vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease) or significant bowel resection that would preclude adequate absorption.
Ophthalmological conditions as follows:
o Intra-ocular pressure >21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure)
o Current or past history of central serous retinopathy or retinal vein occlusion
•Treatment with any investigational product within 28 days of registration
•Pregnant or breast-feeding women.
Due to higher PK exposure, patients of Asian ethnicity may be at a higher risk of adverse events with selumetinib treatment. Selumetinib is not contra-indicated in patients of Asian ethnicity, but the potential increased risk of toxicity should be considered and included as part of the discussion with the patient prior to receiving informed consent
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method