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Aurora B/C Kinase Inhibitor GSK1070916A in Treating Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01118611
Recruitment Status : Completed
First Posted : May 6, 2010
Last Update Posted : May 1, 2013
Information provided by (Responsible Party):
Cancer Research UK

Brief Summary:

RATIONALE: Aurora B/C kinase inhibitor GSK1070916A (GSK1070916A) may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of GSK1070916A in treating patients with advanced solid tumors.

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Drug: Aurora B/C kinase inhibitor GSK1070916A Other: laboratory biomarker analysis Other: pharmacological study Procedure: diffusion-weighted magnetic resonance imaging + PET CT Radiation: fludeoxyglucose F 18 dynomic contrast Phase 1

Detailed Description:



  • To determine and establish the safety profile of Aurora B/C kinase inhibitor GSK1070916A and define the dose-limiting toxicity in patients with advanced solid tumors.
  • To determine the maximum-tolerated dose of Aurora B/C kinase inhibitor GSK1070916A in these patients.


  • To determine plasma pharmacokinetic (PK) parameters following administration of Aurora B/C kinase inhibitor GSK1070916A in these patients.
  • To evaluate tumor response after at least 1 cycle of treatment with Aurora B/C kinase inhibitor GSK1070916A in these patients.
  • To propose a safe dose for Phase II evaluation.


  • To investigate the effects of Aurora B/C kinase inhibitor GSK1070916A on markers of mitosis/cell proliferation and apoptosis in humans.
  • To investigate the metabolism of Aurora B/C kinase inhibitor GSK1070916A in humans.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive Aurora B/C kinase inhibitor GSK1070916A IV over 1 hour once daily on days 1-5. Courses repeat every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients receive escalating doses of Aurora B/C kinase inhibitor GSK1070916A until the maximum-tolerated dose (MTD) is determined. Once the MTD has been defined, 15-18 additional patients are recruited for an expanded MTD cohort in which patients receive Aurora B/C kinase inhibitor GSK1070916A at the MTD. Patients at the expanded MTD cohort must consent to have either tumor biopsies taken or FDG-PET/CT and DW-MRI scans performed.

Patients may undergo tissue, blood, and urine sample collection periodically for pharmacokinetic, pharmacodynamic, and other correlative laboratory studies.

After completion of study therapy, patients are followed up for 28 days.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Primary Purpose: Treatment
Official Title: A Cancer Research UK Phase I Trial to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Aurora B Inhibitor GSK1070916A in Patients With Advanced Solid Tumors
Study Start Date : March 2010
Actual Primary Completion Date : March 2013
Actual Study Completion Date : March 2013

Primary Outcome Measures :
  1. Causality of each adverse event to Aurora B/C kinase inhibitor GSK1070916A and grading severity according to NCI CTCAE Version 4.02
  2. Maximum-tolerated dose (MTD)

Secondary Outcome Measures :
  1. Measurement of PK parameter values for Aurora B/C kinase inhibitor GSK1070916A including AUC, Cmax, Tmax, and half life (all cohorts)
  2. Response assessment (stable disease, partial response, or complete response)
  3. Analysis of phosphohistone H3, Ki67, and cleaved caspase 3 in skin-punch biopsies (all cohorts) and tumor biopsies (at the MTD only)
  4. Analysis of caspase-cleaved cytokeratin 18 in serum samples (all cohorts)
  5. Investigation of metabolite concentration in samples of blood (all cohorts) and urine (at the MTD only)
  6. Safe dose for phase II evaluation

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Eligibility criteria The patient must fulfil the eligibility criteria (listed in Section 4.1.1 and 4.1.2).

Additional eligibility criteria must be fulfilled for the expanded MTD cohort (listed in Section 4.1.3).

4.1.1 Inclusion criteria:

  1. Histologically or cytologically proven solid tumour refractory to conventional treatment, or for which no conventional therapy exists
  2. Life expectancy of at least 3 months
  3. World Health Organisation (WHO) performance status of 0 or 1
  4. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week (Day -7 to Day -1) before the patient goes on study. Laboratory Test Value required Haemoglobin (Hb) ≥ 10.0 g/dL Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) Alanine aminotransferase (ALT) AND aspartate aminotransferase (AST) ≤ 2.5 x ULN unless raised due to tumour in which case up to 5 x ULN is permissible Calculated creatinine clearance (preferably measured by EDTA/ DTPA (isotope method) otherwise to be calculated using Wright formula) ≥ 50 mL/min (uncorrected value)
  5. 18 years or over
  6. Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up

4.1.2 Exclusion criteria:

  1. Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosoureas, Mitomycin-C and six weeks for investigational medicinal products) before treatment.
  2. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the Drug Development Office (DDO) should not exclude the patient.
  3. Known brain metastases.
  4. Patients on therapeutic anti-coagulation with warfarin are excluded. (1mg warfarin for line maintenance is acceptable; conversion to low molecular weight heparin is acceptable but must be done a minimum of seven days prior to the first dose of study drug).
  5. Ability to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have a intra-uterine device and condom, diaphragm with spermicidal gel and condom) for four weeks before entering the trial, during the trial and for six months afterwards are considered eligible.
  6. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception [condom plus spermicide] during the trial and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (e.g. condom plus spermicidal gel) to prevent exposure to the foetus or neonate.
  7. Major thoracic or abdominal surgery from which the patient has not yet recovered.
  8. At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
  9. Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
  10. QTc interval ≥ 450 msecs for men and ≥ 470 msecs for women or other clinically significant electrocardiogram (ECG) abnormalities (QTc preferably calculated using the algorithm in Appendix 6).
  11. Use of medicines known to prolong QTc within 14 days prior to the first dose of study drug (see Category 1 of Appendix 5).
  12. Previous exposure to aurora kinase inhibitors
  13. Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA] - refer to Appendix 4)
  14. History of cardiac ischaemia, cardiac arrhythmias, coronary angioplasty or stenting in the previous 12 months. Patients currently on medication for cardiac arrhythmias are also excluded.
  15. Patients with a known left ventricular ejection fraction (LVEF) <50%. A multi-gated acquisition (MUGA) scan or echocardiogram must be performed if clinically indicated.
  16. Any other condition which in the Investigator"s opinion would not make the patient a good candidate for the clinical trial.
  17. Is a participant or plans to participate in another interventional clinical study, whilst taking part in this Phase I study of GSK1070916A. Participation in an observational study would be acceptable.

4.1.3 Additional inclusion / exclusion criteria for expanded MTD cohort:

Once tolerability has been confirmed in the initial three to six patients of the MTD, further patients in this expanded cohort must either consent to have tumour biopsies taken or having FDG PET-CT and DW/DCE-MRI scans performed. The minimum number of patients required in each part of the expansion cohort is six. The following additional inclusion / exclusion criteria will apply.

For patients consenting to tumour biopsies:

  1. Additional written (signed and dated) informed consent for tumour biopsies must be given.
  2. The patient"s tumour should be amenable to biopsy.

    For patients consenting to FDG PET-CT and DW/DCE-MRI scans:

  3. Additional written (signed and dated) informed consent for FDG PET-CT and DW/DCE-MRI scans must be given.
  4. Patients with diabetes must have their condition under good control (blood sugar less than 10mmol/L).
  5. Patients must be able to tolerate / comply with imaging protocol (i.e. patients with high levels of pain, urinary incontinence, or claustrophobia etc should be excluded).
  6. Patients with tumours known to be poorly FDG avid (e.g. mucinous adenocarcinoma, well differentiated neuroendocrine or hepatocellular carcinoma) or falsely negative (e.g. all tumours less than 5-6mm) are excluded. Refer to Appendix 7 for full list of excluded tumours.
  7. Patients with implanted metallic devices (e.g. pacemaker) are excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01118611

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United Kingdom
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
Barts and the London School of Medicine
London, England, United Kingdom, EC1M 6BQ
Sponsors and Collaborators
Cancer Research UK
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Principal Investigator: Chris Twelves, MD, BMedSci, FRCP Leeds Cancer Centre at St. James's University Hospital
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Responsible Party: Cancer Research UK Identifier: NCT01118611    
Other Study ID Numbers: CDR0000669923
First Posted: May 6, 2010    Key Record Dates
Last Update Posted: May 1, 2013
Last Verified: April 2013
Keywords provided by Cancer Research UK:
unspecified adult solid tumor, protocol specific
Additional relevant MeSH terms:
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Fluorodeoxyglucose F18
Molecular Mechanisms of Pharmacological Action