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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Sheffield Teaching Hospitals NHS Foundation Trust
Sponsor:
Collaborators:
Cancer Research UK Clinical Trials Unit, Birmingham UK
AstraZeneca
Fisher Clinical Services Ltd. (drug supply)
Cancer Research UK (funding)
University of Sheffield
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
  Purpose

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.


Condition Intervention Phase
AIDS-related Kaposi's Sarcoma
Drug: Selumetinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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).

Resource links provided by NLM:


Further study details as provided by Sheffield Teaching Hospitals NHS Foundation Trust:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 37
Study Start Date: June 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Selumetinib treatment
Dose-finding study of selumetinib in combination with HAART (phase I) and efficacy at recommended phase 2 dose.
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01752569

Contacts
Contact: Penella Woll 01142265235 p.j.woll@sheffield.ac.uk
Contact: Laura Crack 01214147627 l.r.crack@bham.ac.uk

Locations
United Kingdom
Brighton and Sussex University Hospitals Recruiting
Brighton, United Kingdom
Contact: Victoria Sellick    01273 696955 ext 3523    Victoria.Sellick@bsuh.nhs.uk   
Principal Investigator: Sarah Westwell         
Addenbrookes Hospital Not yet recruiting
Cambridge, United Kingdom
Contact: Amy Gladwell         
Principal Investigator: Kate Fife         
Beatson Institute Not yet recruiting
Glasgow, United Kingdom
Principal Investigator: Diana Ritchie         
Leicester Royal Infirmary Not yet recruiting
Leicester, United Kingdom
Contact: Amy King    0116 258 6318    amy.king@uhl-tr.nhs.uk   
Principal Investigator: Stephen Nicolson         
Chelsea & Westminster Hospital Recruiting
London, United Kingdom
Contact: Alice Shields    020 3315 6101    Alice.Shields@chelwest.nhs.uk   
Contact: Barbara Paracchini    020 3315 2090 ext 5036    barbara.paracchini@chelwest.nhs.uk   
Principal Investigator: Mark Bower         
University College London Not yet recruiting
London, United Kingdom
Principal Investigator: Siow-Ming Lee         
The Christie Hospital Not yet recruiting
Manchester, United Kingdom
Contact: Smina Shahban    0161 918 7355    smina.shahban@christie.nhs.uk   
Principal Investigator: Michael Leahy         
Royal Victoria Informary Not yet recruiting
Newcastle, United Kingdom
Principal Investigator: Swethajit Biswas         
Sheffield Teaching Hospitals NHS Foundation Trust Recruiting
Sheffield, United Kingdom
Contact: Carol Crabtree    01142 265 229    c.crabtree@sheffield.ac.uk   
Principal Investigator: Penella Woll         
Southampton University Hospital Not yet recruiting
Southampton, United Kingdom
Principal Investigator: Peter Simmonds         
Sponsors and Collaborators
Sheffield Teaching Hospitals NHS Foundation Trust
Cancer Research UK Clinical Trials Unit, Birmingham UK
AstraZeneca
Fisher Clinical Services Ltd. (drug supply)
Cancer Research UK (funding)
University of Sheffield
Investigators
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
  More Information

Additional Information:
Publications:

Responsible Party: Sheffield Teaching Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01752569     History of Changes
Other Study ID Numbers: STH16059, 2011-003099-35
Study First Received: August 17, 2012
Last Updated: December 14, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Sheffield Teaching Hospitals NHS Foundation Trust:
HIV
Kaposi's sarcoma
Anti-retroviral therapy
AIDS

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Sarcoma, Kaposi
AIDS-Related Opportunistic Infections
Sarcoma
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Herpesviridae Infections
DNA Virus Infections
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Vascular Tissue
Opportunistic Infections
Infection
Parasitic Diseases

ClinicalTrials.gov processed this record on July 10, 2014