ANZCTR search results

Bionomics has discovered and is developing BNC105P as a Vascular Disrupting Agent (VDA). VDAs are a novel class of agents that target endothelial cells and pericytes of the already established tumor vasculature, leading to an occlusion (blockage) of tumor blood vessels, thus starving tumors of oxygen and other required nutrients. The disruption of blood vessels that feed tumors represents a promising therapeutic strategy for treating cancer. In addition, BNC105P has a direct anti-proliferative effect on cancer cells. BNC105P is the phosphate ester of BNC105, a small molecule Tubulin Polymerization Inhibitor (TPI), and which has displayed a strong efficacy in renal, breast and colon tumor models and other tumor types. Clinical studies undertaken to date have shown BNC105P, administered as a 10 minute IV infusion on Days 1 and 8 of a repeating 21-day cycle, is tolerated at 16 mg/m2. Upon exposure to hypoxia (a low oxygen environment induced by disruption of tumor blood flow), renal tumors have been shown to upregulate an intracellular signaling pathway termed the ‘mTOR’ pathway, as a survival response. The combined blockade of tumor blood flow (via the use of BNC105P) and the blockade of the mTOR pathway (via the targeted mTOR inhibitor Everolimus) is the underlying rationale behind this trial. This dual blockade may result in improved clinical outcomes for RCC patients who have progressed on other available agents. The randomized phase II component of this trial will compare everolimus alone (a current standard of care) with everolimus plus BNC105P. Progression Free Survival (PFS) at 6 months is the primary endpoint. The study has been powered to detect an improvement in 6-month PFS from 36% for everolimus to 60% with the combination group. Additionally, patients progressing on everolimus alone will be offered BNC105P (a sequential approach), which will provide an opportunity to evaluate the activity of monotherapy with BNC105P alone.

Background: The armamentarium for cutaneous warts is vast, the majority of which are not supported by high quality, randomised, controlled trials. We hypothesised that needling of a pedal wart would create local inflammation and a subsequent cell-mediated immune response against human papillomavirus. The primary objective of this study was to investigate if needling to induce cell-mediated immunity against human papillomavirus is an effective treatment of pedal warts in comparison to liquid nitrogen cryotherapy. A secondary objective of this study was to investigate if the cell-mediated immune response induced by needling is effective against satellite pedal warts. Methods: Eligible participants presenting to the University of Western Australia Podiatry Clinic with pedal wart/s were randomly allocated to treatment — either needling or nitrogen cryotherapy. Only the primary pedal wart was treated during the study. The participants were followed over a twelve-week period with outcome assessments made independently under blinded circumstances. Results: Thirty-seven participants were enrolled in the study with 18 allocated to needling and 19 to liquid nitrogen cryotherapy. Regression of the primary pedal wart occurred in 64.7% (11/17) of the needling group and 6.2% (1/16) of the liquid nitrogen cryotherapy group (p=0.001). There was no significant evidence to suggest needling of the primary pedal wart will result in regression of one or more satellite pedal warts (p=0.615) or complete pedal wart regression (p=0.175). There was no significant difference in pain, satisfaction or cosmesis between the two groups. Conclusions: The regression rate or the primary pedal wart is significantly higher in the needling group compared to the liquid nitrogen cryotherapy group. There is no significant evidence that needling of the primary pedal wart to induce a cell-mediated immune response is effective against satellite pedal warts.

This study aims to investigate radiation-related changes in the lungs using a novel, high-resolution imaging modality, in patients with non-small cell lung cancer. Who is it for? You may be eligible to join this study if you are aged 18 years or above, and are receiving curative intent radiotherapy for non-small cell lung cancer with or without chemotherapy. You should also have had a FDG-PET scan performed for staging of your cancer. Study details: All participants in this study will undergo a Gallium PET scan before radiotherapy treatment, midway through treatment, 3 months after treatment and 12 months after treatment. They will also receive a standard PET scan (similar to the one initially used to diagnose the extent of the cancer) after 3 months after radiotherapy treatment. In addition, lung function tests and 6 minute walk tests will be performed before treatment, mid-way throughout treatment and every 3 months after treatment for up to 12 months. These assessments will enable us to evaluate changes in lung function. By documenting these changes, we aim to better understand the fundamental effects of radiation on pulmonary (lung) physiology, better predict for radiation toxicity, and in the future reduce radiation toxicity by avoiding irradiation of functionally critical segments of lung. In an additional sub-study we will collect blood samples at 5 different timepoints from before treatment to 3 months after radiation treatment, in order to assess radiation induced DNA damage outside of radiation fields.

The burden of stroke due to atrial fibrillation (AF; a common irregular heart rhythm) is high, especially in older persons in whom AF is most common. To prevent stroke in this high-risk population antithrombotic (anti-clotting) medicines must be used. Warfarin is currently the recommended therapy, however, it requires careful monitoring & management to avoid side-effects (eg bleeding), leading some clinicians to choose less effective therapies (aspirin) for their patients. This clinical trial will test the use of a novel computerised clinical tool (CARAT) to assist GPs in assessing their patients risk of stroke versus side-effects from treatment, and recommended treatment based on ‘risk assessment’.

The aim of this project is to understand whether specific FTO risk gene variants influence the skeletal muscle’s ability to utilise carbohydrates and fats at a genetic and tissue level following a 12 week high intensity intermittent exercise training intervention. Ten (10) healthy males with the FTO rs9939609 risk allele (A) and 10 healthy males with two FTO rs9939609 wild type alleles (TT) between the ages 20 - 50 will be recruited to participate in this study. Following a buccal swab and venous blood sampling to obtain a genetic and metabolic signature profile, participants will perform a low (40% VO2max-LO) and high-intensity (80% VO2max-HI) exercise bout for approximately 70 and 38 minutes, respectively. This second test will occur a minimum of 2 days following the commencement of the first exercise test (maximum of up to 1 week). Venous blood will be sampled prior to, immediately after, 15 minutes, and 3 hours following completion of the exercise. Urine samples will be collected prior to and 3 hours following the completion of the exercise. A 12 week exercise training intervention will then be employed. 36 training sessions will be conducted in total over the 12 week period. This intervention will involve participants cycling at 150% VO2max for 20 seconds with 40 seconds passive recovery per minute, and the frequency and duration of sessions will be incremented in 4 x 3 week blocks. Following this intervention the LO and HI exercise tests will be repeated (following the same procedures as indicated above).This project will provide important information on whether low or high intensity exercise is more effective to stimulating glucose and fat metabolism in skeletal muscle, and whether high intensity intermittent exercise training can influence the metabolic profile of those with FTO obesity risk variants. This project may also provide genetically susceptible individuals with an insight in to risk-reducing behaviours that can be effective in prevention of obesity.

Mitotane is the only systemic treatment available for advanced adrenocortical cancer and is toxic, with variable pharmacokinetics (variable drug metabolism between patients). This study aims to achieve ideal plasma levels of the drug quickly by adjustment of the dose based on plasma level, and maintain the plasma level within the ideal range by regular blood level monitoring and dose adjustment. We also aim to study factors that contribute to variability between patients in their metabolism of the drug, and confirm a relationship between drug level and anticancer effect. As a consequence of this study we aim to provide a high quality therapeutic drug monitoring service for clinicians and patients with this disease in Australia.

The use of general anaesthesia (GA) in infants and young children has generally been considered safe. Recent research from laboratory animal studies has raised concerns that exposure to anaesthetic medicines in early life could potentially be related to impaired memory, learning and behaviour. Cystic Fibrosis (CF) is an inherited condition that is usually diagnosed in the first few weeks of life through the newborn screening program. CF leads to serious chest infections and lung damage. To try and identify chest infections and treat them early before they have a chance to cause lung damage, children with CF may undergo many tests and treatments. The ACFBAL study was initiated to examine the use of BAL to direct therapy in young children with CF who are unable to expectorate sputum. This current study takes advantage of the previous randomisation to bronchoscopy directed therapy where children received bronchoscopy and BAL at baseline initially in the first six months of life, and subsequently with exacerbations requiring hospital admission or with Pseudomonas aeruginosa identified from oropharyngeal sampling.

The primary purpose of this study is to explore and describe the clinical decision making of Australian general practitioners involved in the management of blood pressure: how is BP being measured? How is BP being recorded? How is BP being interpreted by the GP and patient? How is BP being managed – lifestyle interventions, medication, as an isolated risk factor or in the context of absolute cardiovascular risk? We also want to explore the barriers and facilitators to the management of blood pressure in Australian general practice: What factors influence the clinical decision-making of the GP?

This study was designed to investigate if differences existed between acute energy consumption and perceived satiety in fatty acid (FA) hypersensitive and hyposenstive subjects following a high fat breakfast.

Abstract Introduction: Myalgia and headache are frequently observed conditions after electroconvulsive therapy (ECT). In this study, we aimed to compare the effects of succinylcholine and rocuronium-sugammadex on myalgia and headache after ECT. Material and Method: Forty five patients undergoing ECT were included in the study. Anesthesia induction was provided with propofol 1 mg/kg and succinylcholine 1 mg/kg in the Group S (n=24), and with propofol 1 mg/kg and rocuronium 0,3 mg/kg in the Group R (n=21). Electroshock was applied after obtaining full muscular relaxation. Sugammadex 4 mg/kg was administered to the group R after the motor seizure. The first three ECT sessions of all the patients were evaluated as regards the time of start of spontaneous respiration following the induction, time of opening the eyes in response to verbal stimuli, and VAS scores for myalgia and headache at hours 2, 6, 12 and 24 following the ECT. Results: There were no significant differences as regards demographic data and hemodynamic data upon comparison of the two groups. The times for the start of the spontaneous respiration and opening the eyes in response to verbal stimuli were found significantly shorter in all the three sessions in the Group R as compared to the Group S (p<0,002). MyalgiaVAS scores at hours 2, 6 and 12 and the headache VAS scores at hours 2 and 6 were significantly higher in the Group S as compared to the Group R (p<0,015). Conclusion: We concluded that the rate of myalgia and headache after ECT was significantly lower in group R than in group S and also the awakening time (spontaneous respiration and opening the eyes in response to verbal stimuli) in group R was significantly shorter than in group S. Key Words: Electroconvulsive therapy, succinylcholine, sugammadex, myalgia, headache