Support an ANZUP research study

Every cent we raise through the Below the Belt Pedalthon and our supporters' kind donations goes directly towards clinical trial research via the Below the Belt Research Fund. In 2017, it provided much needed seed funding to support seven ANZUP members to progress new trial ideas to the point of becoming full scale studies. Read more about the work our members are doing and see the 2017 Pedalthon highlights below.
If you want to help, register for the 5th annual Sydney ride on Tuesday 18 September 2018 or make a donation today.

2017 Research Fund studies

Thank you to all 2017 Below the Belt Research Fund applicants. Congratulations to the following successful applicants. 

Camille Short 

Delivering personalised and evidence-based exercise support to men with metastatic prostate cancer via the internet - A pilot RCT examining intervention impact on behaviour change and quality of life

Both physical activity and psychological support can greatly improve quality of life for men with metastatic prostate cancer. Although it is suggested men are more likely to follow physical activity guidelines than utilise psychological support, traditional supervised exercise is often unavailable and/or underutilised. The key is ensuring physical activity is accessible and affordable, but also individualised, evidence-based and safe. This study will provide personalised physical activity advice through an innovative web-based platform. It will be evaluated to ensure it works as intended and is well received by users and has the potential for significant impact through increased reach and uptake.

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Despite the high morbidity experienced by men with metastatic prostate cancer, and evidence that unmet supportive care needs are higher in this group compared to patients with localised disease (Couper et al, 2010; Sanda et al, 2008), there has been little intervention research aiming to improve quality of life and functional capacity for these patients. Where interventions have been trialled, the focus has predominantly been on psychological interventions, and many of these have had limited success (Chambers et al, 2017).

One potentially promising intervention is physical activity support. Physical activity has been shown to improve both the physical and mental health of men with metastatic prostate cancer (Bourke et al, 2014; Cormie et al, 2013; Moe et al, 2017). It has also been suggested that men may be more likely to adhere to physical activity interventions than psychological interventions, since the performance of physical activity and the outcomes associated with it (building strength and endurance) align with traditional masculine values (Galvao et al, 2016). However, a key challenge is providing physical activity support to men in a way that is easily accessible and affordable, while also individualised, evidence-based and safe. This novel study will address this issue by providing evidence-based physical activity advice through an innovative web-based platform.

While there are some face-to-face programs available, many men live too far away, are too unwell or lack funds to attend face-to-face sessions, especially on an ongoing basis. Our research team, which consists of experts in prostate cancer, exercise physiology, psychology, medicine and telehealth is well placed to develop an alternative support system that will be available to men with metastatic disease via the internet.

Once the website is developed the next step will be to conduct preliminary research to ensure it works as intended and is well received by the initial users.

Megan Crumbaker & Anthony Joshua 

Bipolar androgen therapy (BAT) in men with metastatic castrate-refractory prostate cancer

This study will test the benefit of monthly testosterone injections for metastatic prostate cancer (cancer which has spread outside the prostate) patients on long-term testosterone reducing drugs. Benefits may include an anti-cancer effect, improvements in quality of life and potential for cancer cells to respond positively to drugs that have failed previously. The research will test the possible benefits and increase understanding about this treatment. Additionally, the study aims to improve the ability to select patients who can benefit most from this treatment due to changes in their tumour that might make them more responsive. 

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Androgen deprivation therapy (ADT) remains the mainstay of prostate cancer treatment. Though an effective therapy initially, the side effects of ADT are numerous and treatment resistance is inevitable. Castrate-refractory prostate cancer (CRPC) progresses via adaptive mechanisms that allow ongoing androgen receptor (AR) signaling despite castrate levels of androgens. Preclinical data suggest these adaptive mechanisms may be exploited through the administration of supraphysiologic levels of testosterone, which has been shown to inhibit growth in some androgen-receptor expressing prostate cancer cells. Men with germline and/or somatic DNA repair defects may be particularly sensitive to this treatment.

This study aims to explore the effect of bipolar androgen therapy (BAT) with testosterone enanthate on PSA responses in men with advanced castrate-refractory prostate cancer (CRPC) and DNA repair defects identified on screening circulating tumour DNA (ctDNA) or tumour biopsy.

The research will test the hypothesis while information on treatment effects may be key to appropriate patient selection.

Lisa Horvath 

Statins in Metastatic Castration-Resistant Prostate Cancer (CRPC)

It has been found that certain levels of specific circulating lipids (naturally occurring molecules) in blood are associated with a worse prognosis in men with metastatic castrate-refractory prostate cancer (cancer which has spread to other parts of the body and is able to grow despite hormone therapy). The purpose of this study is to find out if a course of a drug called simvastatin (commonly used to treat high cholesterol, heart disease and diabetes) will lower the specific circulating lipids in blood associated with a worse prognosis.

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To date, biomarker studies in CRPC have mainly focused on changes in the cancer and their effects on therapeutic resistance and prognosis. However, the host environment (i.e. the patient) and its interactions with cancer is increasingly important, in light of the association of prostate cancer and obesity. Our exploratory study was the first to profile the plasma lipidome of men with metastatic CRPC, and to identify and validate plasma lipidomic profiles that are associated with survival in CRPC (Lin et al, Int J Cancer, 2017).

Unsupervised analysis of baseline lipidomic profiles classified patients of a Phase 1 discovery cohort into two groups with significant survival differences (HR 2.31, 95% CI 1.44-3.68, p=0•0005), independent of chemotherapy response. The baseline levels of 46 lipids were individually prognostic, and predominantly sphingolipids. A prognostic three-lipid signature was derived, consisting of ceramide, sphingomyelin and phosphatidylcholine. This signature was associated with shorter overall survival in the Phase 2 cohort (HR 4.8, 95% CI 2.06-11.1, p=0.0003), and was an independent prognostic factor when modelled with clinicopathological factors or metabolic characteristics (Lin et al, Int J Cancer, 2017).

Therefore, a key question is whether therapeutic modulation of a patient’s lipid profile will improve prognosis. However, the first step is to see if lipid modulation therapy can change the circulating lipidomic profile in CRPC patients.

Statins significantly reduces the plasma levels of ceramides, sphingomyelin and cholesterol in those with cardiovascular disease or metabolic syndrome, suggesting that this therapy could change the high risk circulating lipid profile of CRPC patients.

The aim of this study is to assess whether treatment with simvastatin during docetaxel chemotherapy for metastatic CRPC can reverse a poor prognostic circulating lipid signature.

Haryana Dhillon

Patient perception of adherence to treatment advice in urogenital and prostate cancers: a qualitative exploration

It is important people with urogenital and prostate cancers complete their planned treatment and follow-up. However little is known about how this is for patients and how we can help them complete their treatments. We will explore patients’ thoughts about the advice they have been given and what may help or hinder their ability to adhere to treatment advice. We will use this information to develop better support to help patients complete treatments and improve clinical outcomes.

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To achieve optimal patient and disease outcomes in urogenital and prostate cancers it is important patients complete the planned course of anti-cancer treatment(s) and continue regular follow-up and disease surveillance. Adherence to supportive care intervention advice has the potential to alleviate symptoms and ensure that patients are able to complete planned anti-cancer treatment. However, at present little is known about what patients are told about adherence and their perception of this advice. We know little about the barriers and facilitators to adherence to treatment advice in the cancer setting.

It is recognised that treatments resulting in a high side-effect and symptom burden over a prolonged duration of use are likely to result in lower adherence. Risk factors for lower adherence to treatment have been identified more generally in the healthcare literature, including lower literacy, lower health literacy, comorbid illness, and poly pharmacy. However, these factors have not been assessed within urogenital and prostate cancer populations.

This study aims to explore patient adherence to treatment (anticancer, supportive care, follow-up) advice across urogenital and prostate cancers.

Dickon Hayne 

ANZUP co-operative multi-centre cystectomy database (ACCEPT)   

Removal of the bladder as treatment for bladder cancer may be necessary to cure the disease. However this remains one of the most major procedures performed by urologic surgeons and carries significant risks for patients. Despite this, there is a currently a lack of quality research to identify ways to improve patient outcomes. The purpose of this study is to set up Australia’s first national secure online database to allow investigators to analyse treatments currently used by urologists and their associated outcomes and complications after bladder removal. This information will then be used to formulate future randomised controlled trials.

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Radical cystectomy involves significant risk of morbidity and mortality. The risk of any complication is significantly more than 50% and recent reported mortality ranges between less than 1% and more than 8%.[ref] Specific complications after radical cystectomy from previous studies include infection (25%)4, intestinal obstruction (23%)4, wound complications (15%)4, thromboembolic events (8%)4, intestinal anastomotic leakage (3%)2. Other complications include significant bleeding, lymphocoele formation, and erectile and sexual dysfunction [ref]. The primary objective is to create a bi-national (Australia and New Zealand) prospective clinical audit to collect data on outcomes after radical cystectomy surgery and secondarily to hypothesise from acquired data whether specific interventions may achieve improved peri-operative care and outcomes for patients.

Dennis Taaffe 

Exercise Medicine Prior to Open Radical Cystectomy: Feasibility and Preliminary Efficacy

Bladder removal surgery as a treatment for bladder cancer is associated with high complication and hospital re-admission rates, as well as significant risk of morbidity and mortality. This risk is increased for patients with poor physical fitness or overall function. This study will test the benefits of a supervised four-week pre-surgery strength and aerobic exercise program in improving post-surgery outcomes and quality of life. It is the first Australian study to test the feasibility and preliminary effectiveness of pre-surgical exercise with opportunities to then proceed to a larger multicentre Phase III trial.

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Bladder cancer has a poor 5-year survival rate of 53% compared to other common cancers such as prostate and breast cancer (AIHW, 2017). For those with muscle-invasive bladder cancer the primary treatment is radical cystectomy (RC) which involves the surgical removal of the bladder with lymph node dissection and urinary diversion, and a hospital stay of 1-2 weeks. However, RC is a complex, technically demanding and high-risk surgical procedure which is associated with significant morbidity, readmission rates, and mortality (Smith et al., J Urol 2014). Patients with poor pre-operative cardiopulmonary capacity have a higher risk of complications post-surgery and increased hospital length of stay (Prentis et al., BJU Int 2013). Moreover, given the age of the patients (median age at diagnosis is 76 years) as well as the fact that smoking is a major risk factor, patients may have associated pulmonary and cardiovascular diseases which contribute to poorer overall function and quality of life. As a result, enhancing functional capacity prior to RC may reduce the stress of surgery and attenuate the general deconditioning process in the immediate post-surgical period which may reduce the length of hospital stay, complications, and time to return to usual activities.

However, little information is available regarding the feasibility of pre-surgical exercise or the potential beneficial effect that exercise may have prior to surgery in this patient group. Therefore, we propose to undertake a short-term (up to 4 weeks in duration) feasibility and preliminary efficacy exercise trial in men and women scheduled to undergo RC and follow them for 3 months post-surgery. The exercise program will be supervised and consist of resistance and aerobic training undertaken three times per week.

Ben Tran 

iTestis: Bioinformatics for Testis Cancer

iTestis is a user-friendly, multi-disciplinary, web-based testicular cancer database. Data collected within iTestis will provide an accurate description of current Australian practices, facilitate retrospective data research projects, seek to answer biological research questions and provide a platform for registry-based trials. It will also record tissue location information from germ cell tumour patients treated in Australia. Once established, iTestis will become a valuable resource to the wider germ cell tumour community.

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While it is the most common cancer in young men, germ cell tumours (GCT) are rare compared to other cancers. Subsequently, in many instances, enrolling sufficient numbers of patients onto clinical trials is not possible. As a result, clinicians often look to data from retrospective studies undertaken by large international centres to answer these questions. While Australia’s reputation in GCT research remains strong through the leadership of the Germ Cell Subcommittee, the decentralisation of cancer treatment in Australia has made it difficult for any single Australian centre to accumulate sufficient numbers of patients to generate any meaningful research, whether that be clinical, retrospective or translational.

iTestis will enable Australia to make large contributions to the G3 global germ cell collaborative group which conducts multiple retrospective data research projects. It may also give us the impetus to lead some of the projects. Some examples of recent G3 projects include: brain mets (led by Darren Feldman) and risk of VTE during chemotherapy (led by Ben Tran).

Selected centres participating in iTestis will gain patient consent for archival tissue collection/analysis and blood collection/analysis to answer biological research questions and facilitate translational research. The availability of tissue or blood will be indicated within iTestis, so that at a later date, when there is a relevant research project, a query can be made to identify eligible patients with available specimens for translational studies (with approval of the investigators involved). Multiple clinically relevant questions can be answered using such a resource. Additionally, the resource can be used to join international collaborations such as the Craig Nichols led miR371 biomarker for stage 1 disease protocol or the Movember GAP5 biomarkers for platinum resistance protocol.

Following the establishment of iTestis as a robust and reliable registry/database, there will also be capabilities to conduct registry-based randomised-controlled trials (RCT). Registry-based RCTs provide comprehensive data across multiple lines of treatment at no additional cost, with the in-built capacity to compare study eligible and ineligible patients enrolled on the registry for a real-world comparison.

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