A Study of Selumetinib in Patients With Kaposi's Sarcoma (SCART)

This study is currently recruiting participants.
Verified December 2012 by Sheffield Teaching Hospitals NHS Foundation Trust
Sponsor:
Collaborators:
Cancer Research UK Clinical Trials Unit, Birmingham UK
AstraZeneca (funding)
Fisher Clinical Services Ltd. (drug supply)
Cancer Research UK (funding)
University of Sheffield (Chief Investigator's employer)
Information provided by (Responsible Party):
Sheffield Teaching Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01752569
First received: August 17, 2012
Last updated: December 14, 2012
Last verified: December 2012

August 17, 2012
December 14, 2012
June 2012
June 2014   (final data collection date for primary outcome measure)
  • Objective Response Rates [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Toxicity of Selumetinib in combination with HAART. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    The primary outcome measure is to identify the safe recommended phase II dose using CTCAE version 4.0 criteria to assess dose limiting toxicity.
Same as current
Complete list of historical versions of study NCT01752569 on ClinicalTrials.gov Archive Site
  • PBMC sub-study [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
    Analysis of PBMC in a sub-study
  • Number of completed cycles [ Time Frame: 2.5.years ] [ Designated as safety issue: No ]
    The number of cycles of Selumetinib treatment in combination with HAART.
  • HIV viral load and CD4 count [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • HAART Drug levels [ Time Frame: 1 years ] [ Designated as safety issue: No ]
    Phase I only
  • Selumetinib and metabolite serum levels [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Phase I only
  • Serum angiogenic biomarkers levels [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Pharmacodynamic measures of Selumetinib in combination with HAART - serum angiogenic biomarker levels and pERK in tumour tissue.
Same as current
Not Provided
Not Provided
 
A Study of Selumetinib in Patients With Kaposi's Sarcoma
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).

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.

Not Provided
Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
AIDS-related Kaposi's Sarcoma
Drug: Selumetinib

Dose schedule:

-1 75 mg od (75 total) --

  1. (starting) 50 mg bd (100 total)
  2. 75 mg bd (150 total)
  3. 100 mg bd (200 total) Selumetinib should be taken twice daily approximately 12 hours apart with water (for BD doses), at least 2 hours after a meal and 1 hour before the next meal. Selumetinib capsules will be administered in a continuous 21 day cycle (6 cycles), unless disease progression occurs.
Other Name: AZD6244
Experimental: Selumetinib treatment
Dose-finding study of selumetinib in combination with HAART (phase I) and efficacy at recommended phase 2 dose.
Intervention: Drug: Selumetinib

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
37
December 2014
June 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically confirmed KS.
  • Measurable disease according to ACTG criteria.
  • Evidence of disease progression in the past 6 months, without anticancer treatment since progression.
  • 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 collection).
  • 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

Exclusion Criteria:

  • 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 study.
  • Refractory nausea, vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease) or significant bowel resection that would preclude adequate absorption.
  • Treatment with any investigational product within 28 days of registration
  • Pregnant or breast-feeding women.
Both
18 Years and older
No
Contact: Penella Woll 01142265235 p.j.woll@sheffield.ac.uk
Contact: Laura Crack 01214147627 l.r.crack@bham.ac.uk
United Kingdom
 
NCT01752569
STH16059, 2011-003099-35
Yes
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield Teaching Hospitals NHS Foundation Trust
  • Cancer Research UK Clinical Trials Unit, Birmingham UK
  • AstraZeneca (funding)
  • Fisher Clinical Services Ltd. (drug supply)
  • Cancer Research UK (funding)
  • University of Sheffield (Chief Investigator's employer)
Principal Investigator: Mark Bower, Professor Chelsea & Westminster Hospital
Principal Investigator: Diana Ritchie, Dr. Beatson Institute, Glasgow
Principal Investigator: Sarah Westwell, Dr. Brighton and Sussex University Hospital
Principal Investigator: Michael Leahy, Dr The Christie Hospital, Manchester
Principal Investigator: Swethajit Biswas, Dr Royal Victoria Infirmary, Newcastle
Principal Investigator: Kate Fife, Dr. Addenbrookes Hospital, Cambridge
Principal Investigator: Stephen Nicolson, Dr. Leceister Royal Infirmary
Principal Investigator: Siow-Ming Lee, Professor University College, London
Principal Investigator: Peter Simmonds, Dr. Southampton University Hospital
Sheffield Teaching Hospitals NHS Foundation Trust
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP