Prof Peter Gibbs

A reliable biomarker of minimal residual disease could have a major impact on adjuvant therapy decision making and the development of new adjuvant treatments. Our initial studies in colorectal cancer and pancreatic cancer have shown that circulating tumour DNA (ctDNA) is a powerful prognostic biomarker. Patients with detectable ctDNA after curative intent surgery have been shown to have a markedly elevated risk of recurrence (well in excess of the average for that patient population), whereas patients with no detectable ctDNA have a much lower risk of recurrence (much less that the average for that patient population). Prospective randomized studies are exploring the potential of a ctDNA directed approach to adjuvant therapy whereby patients with detectable ctDNA have treatment intensified and those with undetectable ctDNA have less intense treatment. World first randomized studies have completed recruitment (stage II colon cancer) or are ongoing (stage III colon cancer, locally advanced rectal cancer and pancreatic cancer). An observational study has been completed in ovarian cancer.

Contact:
DYNAMIC-RECTAL@mh.org.au
DYNAMIC-III@mh.org.au
DYNAMIC-P@mh.org.au
Dynamic-Ovarian@mh.org.au
http://www.anzctr.org.au/

Results from the Dynamic II study have been recently published.
Recently publlished from the ASCO 2022 https://www.asco.org/about-asco/press-center/news-releases/liquid-biopsy-can-help-identify-need-adjuvant-therapy-stage-ii

Professor Peter Gibbs started work in cancer registries with the colorectal cancer registry in 2009. Over time other disease registries have been developed to collect clinical information for a specific area of interest, and depending on the depth of clinical detail captured, can support a variety of research questions.

Longitudinal follow up within a registry, as well as potential data linkage to other routinely collected data software, eg electronic health records or National Death Index, allows for sound representation of real-world patients.

Real World Data collection in a number of cancers started at the Gibbs Lab in 2000, with colorectal cancer followed by breast, pancreas, gastro-oesophageal, brain, prostate, kidney, bladder, testicular, lung and melanoma.

Most recently head and neck cancers have been added to the collection of real world cancer data being undertaken in the Gibbs Lab.

CRC Accord/TRACC team: Professor Peter Gibbs, clinical support from Doctors Vanessa Wong, Hui-Li Wong, Iris Tung, Matthew Loft and Kate Dunne. project management and study coordination by team led by Michael Harold, Catherine McKay, Sharen Gibbs, Kelsey Serena and team of clinical data officers.

Breast cancer, Tabitha/ARORA HER2+, ER+ breast cancer team: Dr Sheau Wen Lok, clinical support from doctors, Vanessa Wong and Iris Tung. Project management support from Catherine Morton and team of clinical data officers.

Pancreas cancer, PURPLE pancreas cancer team: Dr Belinda Lee, clinical support from Doctor Richard To, Shehara Mendis, project management support from Nadia Ayres, Michael Harold and team of clinical data officers.

Gastro-oesophageal cancer, GATOR team: Dr Margaret Lee clinical support from Dr Grace Gard and project management support from Catherine McKay and team of clinical data officers.

Brain, BRAIN Brain cancer team: Clinical Lead Dr Lucy Gately, project management support from Megan Dumas and team of clinical data officer.

Genito-urinary cancers – prostate (Epad), kidney (KRAB), bladder (BLADDA), testicular (itestis) Clinical Lead Associate Professor Ben Tran with clinical support from Doctors Arsha Anton, Ciara Conduit, Elizabeth Liow and Andrisha-Jade Inderjeeth and project management support from Sophie O’Haire and Kristina Zlatic, Mary Moody and clinical data officers

Lung, INHALE led by Dr Ben Markman with clinical support from Doctor Sam Smith and project management support from Siobhan Gallus and team of clinical data officers.

Melanoma, MASTER lead by Dr Miles Andrews and project management support from Tina Cavicchiolo and team of clinical data officers.

Head and neck, ENHANCE lead by Professor Peter Gibbs with clinical support from Dr Shehara Mendis and project management support from Catherine McKay.

The Gibbs Lab has engaged with over 35 hospitals across Australia, New Zealand and Singapore. More recently we have been engaging with hospitals in South Korea to contribute to the real world data collection of cancer data across the multiple registries. These data registries hold comprehensive de-identified data on thousands of patients that can be shared with our collaborative partners to create large scalable datasets which provides valuable insights into the real-world patient landscape and changing patterns of care across Australia and internationally.

Led by Professor Peter Gibbs and supported by Doctors Vanessa Wong, Lucy Gately, Associate Professor Ben Tran and Dr Steven David and project management team of Michael Harold, Catherine Morton, Megan Dumas, Roslynn Murphy, Siobhan Gallus, Kristina Zlatic and Sophie O’Haire.

Registry Clinical Trials combines conventional trial methodology with registry systems to produce real-world clinical evidence.

Registry based trials integrate the high internal validity (elimination of bias) of randomised clinical trials with the high external validity (applicable to a clinical setting) associated with enrolling real-world patients through a registry. These studies are addressing simple but important questions in the routine of common cancers, exploring issues not addressed in conventional clinical trials such as the optimal treatment sequence, combination or duration of available therapies.

Working with partners across the Victorian Comprehensive Cancer Centre (VCCC) alliance and private health services, the first Australian cancer-focused registry trials will investigate and evaluate promising new cancer treatment strategies for bowel cancer and brain tumours.

Registry trials are enabled by the comprehensive clinical data captured in clinical registries at many hospitals, including all VCCC partner hospitals, enabling researchers to compare the impact of different treatment strategies on large numbers of patients in a real-world setting.

Conventional cancer clinical trials typically have strict patient eligibility criteria, limiting patient access. For less common types of cancers, this can restrict researchers’ access to enough patients to draw statistically valid conclusions, high external validity through inclusion of real‐world patients and smaller centres. They can answer simple, pragmatic questions that are otherwise unlikely to ever be explored. There is rapid patient recruitment due to broad eligibility criteria.

Data collection is integrated into routine care and they substantially lower costs than conventional randomised clinical trials.

ALT-TRACC – investigating alternating two cycles of doublet chemotherapy versus standard continuous doublet chemotherapy as a new treatment strategy for newly diagnosed metastatic colorectal cancer

EX-TEM – examining the effectiveness of six months versus 12 months of post-radiation chemotherapy for glioblastoma, an aggressive form of brain cancer

REAL Pro – Registry-based study of Enzalutamide vs Abiraterone assessing cognitive function in elderly patients with metastatic castration-resistant prostate cancer.

AVATAR – Stereotactic Radiotherapy for Oligoprogressive ER-positive Breast Cancer

Email: registrytrials@mh.org.au
http://www.anzctr.org.au/

New trials are currently under development in brain, lung and colorectal cancer.

Reference and further reading
A comparison of conventional clinical trials and registry-based randomised controlled trials in multidisciplinary cancer care:

Foroughi S, Wong HL, Gately L, Lee M, Simons K, Tie J, Burgess AW, Gibbs P. Re-inventing the randomized controlled trial in medical oncology: The registry-based trial. Asia Pac J Clin Oncol. 2018 Jun 26. doi: 10.1111/ajco.12992.

Defining key design elements of registry-based randomised controlled trials: a scoping review

Karanatsios, B., Prang, KH., Verbunt, E, Yeung JM, Kelaher M & Gibbs P. Defining key design elements of registry-based randomised controlled trials: a scoping review. Trials 21, 552 (2020). https://doi.org/10.1186/s13063-020-04459-z

Organoids are three dimensional models derived from patient tissue taken from tumour resections that mimic the function and structure of the cancer.

Using these laboratory models, creating miniature cancers in pancreas, colorectal, head and neck, brain, derived from patient biopsies, we have partnered with other labs in the Personalised Oncology division with expertise in organoid development.

The studies of patient derived tumour organoids in these specialities ultimately aims to conduct in vitro sensitivity testing and for this to be being used to guide clinical treatment selection.

Each program is led by Professor Peter Gibbs with Lead Clinician assistance with Dr Lucy Gately, Dr Belinda Lee, Dr Iris Tung, Dr Shehara Mendis, Dr Grace Gard with project managment support from Helen Brasier, Catherine McKay, Kelsey Serena and Matt Chapman.

All clinicians have appropriate sub-speciality expertise and substantial clinical appointments with other medical oncologists and participating centres around Melbourne and regional Victoria. The ultimate focus being clinical relevance and impact.

The Gibbs Lab is partnering with other labs within the Personalised Oncology division at WEHI, such as the Seiber Lab and Putoczki Lab to undertake this work.

Assessing Predictive and Prognostic Biomarkers in Pancreatic Cancer

Establishing a biobank of colorectal and pancreatic cancer models for the pursuit of personalised therapies

Establishing a BioBank of Oral Cavity Squamous Cell Carcinoma Organoids for Improving Drug Testing and Treatment

BioBrain: Brain Tumour Organoid and PDX Projects

Contact: organoids@wehi.edu.au
http://www.anzctr.org.au/

Partnering with cooperative groups such as the AGITG the Gibbs Lab is now managing all aspects of clinical trial management for a number of interventional studies. The collaborative group members are medical oncologists that work across a number of participating institutions who have worked together to design, conduct and analyse clinical studies.

The projects required clinical trial infrastructure support such as protocol review, database build and support, drug management, safety reporting. All aspect of this are offered by the Gibbs Lab coordinating centre. This work is being led by Associate Professor Jeanne Tie with clinical support from Dr Shehara Mendis and Dr Wei Hong, project management support from Tina Cavicchiolo and Thy Nguyen.

RESOLUTE : Randomised Phase II Trial to Evaluate the Strategy of Integrating Local Ablative Therapy with First-Line Systemic Treatment for Unresectable Oligometastatic Colorectal Cancer

Contact: rmh-resolute@mh.org.au

NEO-adjuvant chemo-IMmunotherapy in PAnCreaTic cancer, NEO-IMPACT.
contact neo-impact@mh.org.au

http://www.anzctr.org.au/
https://gicancer.org.au/clinical-trial/status/open/