This project aims to engage with an Australasian group who set up trials which are ‘public good’ (not commercial). In this pivotal clinical trial, Andrew will be working with this group, called the Australasian Gastrointestinal Trials Group (AGITG) on a trial called MASTERPLAN.

This trial will bring a new kind of radiotherapy to Auckland City Hospital, called stereotactic ablative radiotherapy (SABR). This trial will be looking at how safe this therapy is with combined with chemotherapy in some particular kinds (in locally advanced (LAPC) or borderline resectable (BRPC)) of pancreatic ductal adenocardinoma (PDAC). This kind of trial is called an ‘early phase’ trial and generally involves small numbers of patients, to ensure the intervention is safe to use. Once this trial format is complete, the trial will move to an ‘efficacy’ phase, where larger numbers of patients are offered the intervention and the direct results of benefit are outlined. This treatment is not currently funded in New Zealand, so this trial creates an opportunity for New Zealanders to access this innovative treatment, while in combination with standard of care chemotherapy. This treatment will be used instead of conventional radiotherapy in the trial group. Compared to conventional radiotherapy, SABR is considerably shorter (1.5 weeks compared to 5 weeks of treatment) and is less toxic.

Introducing this technique in trial format will bring this new treatment to New Zealand in pancreatic cancer for the first time, but it will also ensure the introduction is safe, closely monitored, and benchmarked in order to meet external quality assurance standards (facilitated by the involvement of the Trans Tasman Radiation Oncology Group). TROG quality assurance will include credentialing of the end-to-end SABR pathway, as well as independent review of SABR treatment plan pre radiotherapy for each patient, and post treatment technical QA review. This will enable this pathway to be used in future.

The researchers have recently undertaken two trials in this technique in prostate cancer. In future, they wish to work with the Auckland Cancer Society Research Centre, a pillar of the Centre for Cancer Research, to develop a new chemotherapy drug to be used in combination with this radiotherapy treatment.

The introduction of pancreatic SABR will strengthen the te whare tapa whā model of care to help address disparities in Māori outcomes. Introducing a pancreatic SABR programme will create new opportunities for translational research. This research will create a technology platform which will support future trials and access to this treatment. In future we will be able to combine this treatment with a chemotherapy drug being developed at the University of Auckland.

Specifically, this study aims to:

1. To develop a te whare tapa whā model of care around the clinical implementation of pancreatic SABR.

2. To recruit 3 patients onto the Masterplan protocol. An application will be made to the NZ Gut Foundation (NZGF) to fund an additional 3 patients for total of six (preliminary approach to NZGF already made by Canterbury DHB); this should ensure at least 4 patients are treated on the SABR arm.

3. To compare radiosensitisation by lead DNA-PKi (SN39536) and corresponding HAP (SN39884) in a murine PDAC cell line (Panc-02) in vitro, and radiosensitisation of Panc-02 tumours and duodenum in mice. (this will begin work on a future study using a NZ developed chemotherapy drug in combination with the SABR).

The study design is a randomised control trial with randomisation 2:1, which means more patients will be on SABR than a regular 1:1 RCT. Both arms receive 6 x 2 week cycles of FOLFIRINOX chemotherapy (or an alternative if they cannot tolerate this chemotherapy regime). SABR (40 Gy in 5 fractions) is administered within 4 weeks of last chemotherapy cycle. Surgery is aimed to be performed 6 weeks after completion of chemotherapy +/- SABR. The option for patients of participating in tissue and blood sample collection (Te Ira Kāwai | Auckland Regional Biobank) for future biomarker research (conducted by AGITG) will be available.

A key outcome of this study will be to see if the SABR improves control of the cancer. The most important outcome will be to see if this is controlled 12 months after the treatment. The researchers will also consider the safety, surgical outcomes, how long peoples cancer stays impaired (not growing), rates of surgery, pathology, quality of life, and some kinds of survival measures (how long people live and how well, after treatment).

Glioblastoma (GBM) is the most common, debilitating, and fatal brain tumour in adults. Despite many advances in anticancer therapies, GBM still lacks any curative interventions, resulting in a median survival time of only 16 months.   

We aim to develop a digitised method of accurately identifying distinct GBM tumour microenvironments (TMEs) and elucidate their biological features that could be exploited for personalised diagnosis and treatments.   

The first objective will use machine learning to develop an image analysis algorithm. This algorithm aims to identify unique TME signatures from patient tumours –a “tumour fingerprint”, which can act as a stand-alone, rapid, and personalised GBM diagnostic system.  

The second objective will consider the relevant cell populations and protein expression of the identified TMEs, using tissue and cells isolated from patient GBM specimens. Immunohistochemistry-based single-cell image analysis and flow cytometry will be utilised to uncover prognostically applicable TME-associated information, which will further advance our understanding of GBM biology and identify potential therapeutic targets.  

In the future this will lead to research producing a multiscale predictive algorithm that can guide personalised treatment strategies and drug development for GBM. We believe our project will provide a widely accessible and equitable diagnostic system that delivers rapid, low-cost and personalised tumour diagnostics.  

Lung cancer is the leading cause of cancer death for Māori, who suffer higher incidence and mortality than non-Māori. Inequity occurs at all parts of the cancer journey. This project employs patient and whānau voice early to create a Māori lung cancer cohort that is most likely to recruit and ultimately benefit Māori through collaboration. Specifically, this award will prepare for the cohort using wānanga, patient/whānau interview, Māori expert consultation and scientific workshops. This seeding project aims to:  

1. Determine the feasibility of a prospective cohort of Māori lung cancer patients recruited from the clinical setting.  

2. Establish and demonstrate patient engagement, a data management plan that meets obligations of Māori data sovereignty and a dissemination strategy to impact Māori health.  

3. Formalise academic/clinician collaborations in four modules: patient experience, immunoprofile, genomics and tissue feasibility/biobanking.  

These new understandings will provide the base for a large HRC application in 2023 lead by UoA. 

Annette recently assembled a multidisciplinary team from across New Zealand that successfully competed for a prestigious programme grant from the Breast Cancer Foundation NZ to study young NZ women with breast cancer. The team includes biomedical scientists, bioinformaticians and statisticians, a medical oncologist and pathologist. She now plans to expand this translational research team to include people and groups with expertise outside of their own.  

The overarching goal of our work is to perform research that will translate into improved and equitable outcomes for women with breast cancer in New Zealand. This ‘released time’ will be used to 

• establish partnerships with Māori and Pacific groups to ensure that we are addressing questions relevant to them and their whānau, 
• form relationships with Māori, Pacific and other patient advocate/support groups, 
• expand the expertise base of our team by establishing collaborations with health economists, epidemiologists and clinicians of different specialities that treat women with breast cancer, 
• establish links with BreastScreen Aotearoa, and 
• hold hui with the team to discuss future collaborative work. 

Having this extended multidisciplinary team will enable us to generate results that are robust and relevant, to be able to make recommendations to health policy makers and lead to transformations in clinical practice.   

Malnutrition (under-or over-nutrition) is common among paediatric cancer patients and impacts survival, treatment tolerance and quality of life.  Evaluating nutritional status is an integral component of care during cancer treatment; however, it is not routinely undertaken in NZ. As a result, the factors influencing change in nutritional status during childhood cancer remain poorly understood, and malnutrition prevention is challenging to implement.   

This research will determine the feasibility of measuring the change in nutrition-related blood, body measurements, and body composition in the first 12 months of treatment in a sample of newly diagnosed children <18 years with cancer at the Starship Blood and Cancer Centre (SBCC) in Auckland, NZ.   

Data collection points will be at diagnosis, 3, 6, 9, and 12 months from diagnosis. Collected data will be classified into five domains; 1) anthropometrics; 2) biochemical data; 3) medical tests and procedures; 4) food/nutrition-related history; and 5) nutrition-focused physical findings.   

Outcomes include determining the occurrence of micronutrient abnormalities and malnutrition, measuring changes to body composition and dietary intakes, and assessing the impact of nutritional status on clinical outcomes. The proposed collaboration between the University of Auckland, SBCC and the National Child Cancer Network will be the first to provide NZ-specific data in this area of nutritional science and guide better health outcomes.   

They key cancer focus of this research is testing and development of new drugs which will work against HPV (human papillomavirus) negative head and neck cancer.

HPV is a group of viruses that are passed between people through various routes and can have an impact on abnormal cell growth which can lead to several kinds of cancer.

This drug has been developed by the Auckland Cancer Society Research Centre and has been tested in healthy people already.

This research undertakes an early trial of this medication in people with cancer, testing the drug on its own, and in combination with another common cancer treatment, radiation therapy, before patients go for surgery to remove their cancers.

The drug works by a complicated process of targeting a section in the middle of the tumour which has limited oxygen, killing the cells. Because the drug targets only a part of the tumour, the developers think there will be fewer side effects than other treatments.

The key cancer focus for this clinical trial is the use of selenium (type and dose) in the treatment of bowel cancer.

This trial will recruit patients from Counties Manukau DHB and Waikato DHB who are enrolled in the bowel screening programme. Patients will have already had removal of the bowel cancer precursor, polyps. Different doses and types of selenium will be tested in this group, to see which most helpful, and which option is more tolerable for people (has the least side effects, although few are expected). People will also be tested to see how much selenium they have in their blood before starting on selenium, to see if that makes a difference to their polyps reoccurring.

This trial will help inform a larger trial which will help determine whether the dose and type of selenium identified in this project are working to reduce reoccurring polyps. This future trial will recruit much larger numbers of people.

The key cancer focus of this research is endometrial cancer, a gynaecological cancer which is affected by weight and disorders relating to the metabolism. This cancer can be challenging to diagnose. This cancer has implications for Maori and Pacific women and may affect women before they have children. This is a study in two parts, running at the same time.

One part is research which will take place in the laboratory. This part will apply a new technique, first in the world, to the analysis of cancer tissues. This technique uses a new way to identify cancer biology and biomarkers (medical signs about things that happen in cells, in this case happening in the cancer cell) called extracellular vesical investigation. The team will use donated tissue from the Auckland Biobank.

Biomarkers are important because what happens in the cell can tell us the best way to stop the cancer spreading or progressing. In future, this will help us with both diagnosis of endometrial cancers and monitoring of people who already have endometrial cancer. This technique might also be useful in diagnosis and management of other cancers in due course.

The other part is establishment of a research network of cancer clinicians and researchers. This network will identify focus areas and areas of need for endometrial cancer patients in New Zealand. They will do this by:

·       connecting researchers and clinicians with various areas of interest,

·       establishing partnerships between researchers, and

·       organising the research studies in this area by ensuring there is minimal overlap and that complementary studies are combined.

This will ensure we have efficient and useful research on this unique and important cancer.