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

NCT01118611 | Completed Phase 1

• 3 other identifiers: CDR0000669923CRUK-CR0802-11EUDRACT-2008-005031-15
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (2)

• Causality of each adverse event to Aurora B/C kinase inhibitor GSK1070916A and grading severity according to NCI CTCAE Version 4.02

• Maximum-tolerated dose (MTD)

Secondary Outcomes (6)

• Measurement of PK parameter values for Aurora B/C kinase inhibitor GSK1070916A including AUC, Cmax, Tmax, and half life (all cohorts)

• Response assessment (stable disease, partial response, or complete response)

• Analysis of phosphohistone H3, Ki67, and cleaved caspase 3 in skin-punch biopsies (all cohorts) and tumor biopsies (at the MTD only)

• Analysis of caspase-cleaved cytokeratin 18 in serum samples (all cohorts)

• Investigation of metabolite concentration in samples of blood (all cohorts) and urine (at the MTD only)

Interventions

Aurora B/C kinase inhibitor GSK1070916A DRUG

laboratory biomarker analysis OTHER

pharmacological study OTHER

diffusion-weighted magnetic resonance imaging + PET CT PROCEDURE

fludeoxyglucose F 18 dynomic contrast RADIATION

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically proven solid tumour refractory to conventional treatment, or for which no conventional therapy exists
• Life expectancy of at least 3 months
• World Health Organisation (WHO) performance status of 0 or 1
• 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)
• years or over
• Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up

You may not qualify if:

• 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.
• 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.
• Known brain metastases.
• 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).
• 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.
• 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.
• Major thoracic or abdominal surgery from which the patient has not yet recovered.
• At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
• Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
• 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).
• Use of medicines known to prolong QTc within 14 days prior to the first dose of study drug (see Category 1 of Appendix 5).
• Previous exposure to aurora kinase inhibitors
• Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association \[NYHA\] - refer to Appendix 4)
• 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.
• Patients with a known left ventricular ejection fraction (LVEF) \<50%. A multi-gated acquisition (MUGA) scan or echocardiogram must be performed if clinically indicated.

Sponsors & Collaborators

• Cancer Research UK: lead

Study Sites (2)

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

Barts and the London School of Medicine

London, England, EC1M 6BQ, United Kingdom

Location

Study Officials

• Chris Twelves, MD, BMedSci, FRCP

  Leeds Cancer Centre at St. James's University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2010
• First Posted: May 6, 2010
• Study Start: March 1, 2010
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: May 1, 2013

Record last verified: 2013-04

Locations

GB (2)