Pancreatic cancer clinical trial program to target genome and scar tissue

A national clinical trial program will test promising new targeted therapy for pancreatic cancer, one of the deadliest forms of cancers of which more than 3000 cases are diagnosed annually in Australia alone.

The clinical trial program (MoST–P), led by researchers and clinicians at UNSW Sydney and the Garvan Institute of Medical Research, will provide patients with access to either targeted therapies matched to the genomic signature of their individual tumour, or targeted to the tumour environment.

The trial is supported by a $3.75 million Cancer Institute NSW Translational Program Grant and is scheduled to begin later this year.

“For the first time, this proposal brings together scientists, clinicians, and the community, within a proven national program to achieve meaningful outcomes for Australians affected by pancreatic cancer. It is a tangible dividend of the years of funded research by focused pancreatic research groups within the UNSW pancreatic research hub,” says Professor David Goldstein, chief investigator from UNSW Sydney.

Investigator Professor David Thomas from the Garvan Institute says: “NSW has a critical mass of excellence in pancreatic cancer. This trial is a really exciting bench to bedside translation of our research findings for pancreatic cancer patients and gives us new options to target the surrounding tissue and improve drug response for patients with this disease.”

A new approach to treating pancreatic cancer

Pancreatic cancer is one of the most lethal forms of cancer, with a five-year survival of less than 9% in Australia. Pancreatic tumours often show no obvious signs or symptoms in the early stages of the disease, and by the time most cases are diagnosed, cancer has already begun to spread outside the pancreas and is often inoperable.

Through the trial, Garvan and UNSW Sydney researchers will treat pancreatic cancer patients by using genetic information or targeting the tumour environment, known as the stroma.

The research team is working with Garvan’s successful Molecular Screening and Therapeutics (MoST) trials program, where the genome of pancreatic cancer patient’s tumour is sequenced and matched to available treatments, at a number of different sites throughout Australia.

If no matched treatment is available, patients will be placed in one of two trials testing the efficacy of therapies targeting the stroma, which in pancreatic cancers can form an impenetrable barrier to treatment. These two treatments, RXC004 (trial led by the Garvan Institute in collaboration with biotech Redx) and sulfasalazine (trial led by UNSW Sydney), have both been shown to target the scar tissue around pancreatic cancers and prevent tumour growth in experimental models.

“The two pancreatic cancer sub-studies aim to tackle what is currently a critical barrier to existing treatments – the scar tissue barrier around pancreatic tumours,” says investigator Associate Professor Marina Pajic from the Garvan Institute. “Our approach in this trial is a real step towards personalised medicine and pancreatic cancer, involving co-targeting of the cancer genome and specific signals from the stroma targeting.”

World-leading collaboration

This trial will integrate the research and clinical expertise of the Australian Pancreatic Cancer Genome Initiative (APGI), the Australian Pancreatic Cancer Matrix Atlas (APMA) and the UNSW Sydney pancreatic cancer hub, with the national clinical framework of the MoST clinical trials program.

“New South Wales has been internationally acknowledged as research leaders in pancreatic cancer,” says investigator UNSW Associate Professor Phoebe Phillips.

“This clinical trial will employ a systematic mechanism to bring the laboratory findings to patients, in a meaningful timeframe, to improve treatment. As a scientist, I am really proud that we have taken basic scientific findings previously supported by NHMRC and PanKind (The Australian Pancreatic Cancer Foundation) into the clinical setting.”

Investigator Professor Paul Timpson from the Garvan Institute says: “This crucial clinical trial will leverage the MoST clinical trial framework to improve outcomes for this aggressive cancer. We expect to demonstrate the value of understanding the tumour and scar tissue profile of pancreatic tumours for treating pancreatic cancers in real-time. Our deep analysis of samples involved in this trial will guide new targeted drug therapies worthy of larger clinical trial testing, which we hope will ultimately improve and personalise treatments for all patients.”

Source: Garvan Institute