Thanks to an $3.75 million grant injection from the Cancer Institute, NSW Translational Program, researchers and clinicians from UNSW and the Garvan Institute in Australia will head a clinical trial program called MoST-P, part of a national program investigating novel therapeutics for pancreatic cancer, one of the deadliest cancers with 3,000 Australian cases diagnosed per year. Part of the personalized or precision medicine revolution, this study affords patients access to therapies that match to the genomic signature of each patient’s specific tumor, or targeted generally to the tumor environment. Led by chief investigator David Goldstein, a UNSW Professor and Director of the Translational Cancer Research Network, Vlado Perkovic, UNSW Dean of Medicine & Health is upbeat about the prospects for pancreatic cancer patient outcomes with this more personalized investigational method. This initiative is the result of an intense and committed group of institutions and investigators targeting pancreatic cancer in New South Wales, Australia.
Pancreatic cancer is one of those things many people just don’t want to think about. It can strike, and usually does, when we least expect it. It’s a type of cancer that reveals itself at the worst possible time, at the later stage, after the spread of the cancerous cells throughout the body.
According to the statistics from the Pancreatic Cancer Action Network (PANCAN), this form of cancer is the world’s third most deadly. With a five-year survival rate of 10%, it’s the world’s “toughest” cancer as well. In America alone, over 60,000 people will be diagnosed with pancreatic cancer and about 48,220 will die due to this disease.
Pancreatic Cancer Research Hub
MoST-P is part of a larger initiative targeting pancreatic cancer research known as the Pancreatic Cancer Research Hub, which involves the coming together of top research, clinician and scientific talent from NSW health districts, hospitals, universities and research institutes: all on a mission to boost pancreatic cancer survival percentages. The partnership that emerged between the Pancreatic Cancer Research Hub and the MoST-P trial led to the recent $3.75 million grant.
There is a lot of important efforts here in New South Wales, suggests TrialSite, based on the collaborative energies, focus and progress. UNSW Associate Professor Phoebe Phillips went on the record, “New South Wales has been internationally acknowledged as a research leader in pancreatic cancer.”
Moreoverm the MoST-P trial integrates the clinical expertise of the Australian Pancreatic Cancer Genome Initiative (APGI), the Australian Pancreatic Cancer Matrix Atlas (APMA) and the UNSW Sydney pancreatic cancer hub, as well as the national clinical framework of the MoST clinical trials program.
The Novel Approach
The successful program out of Garvan called Molecular Screening and Therapeutics (MoST) trials program involves the sequencing of the patient’s pancreatic cancer tumor and then matched to available treatments at a number of Australian research sites. In this way, the clinical trial takes on a personalized focus as the clinical investigators will study each patient’s genetic information or in a precise way target the patient’s tumor environment called the stroma. Note that with some pancreatic cancer patients, the stroma can turn into a sort of impenetrable barrier to treatment as reported in the UNSW newsroom press release.
For those patients that the researchers cannot find a match treatment then they will be enrolled into one of two novel clinical trials investigating the efficacy of therapies targeting the stroma in a quest to overcome the barrier effect.
What are the Treatments?
This study involves two treatments as reported by UNSW including (1) RXC004 which involves the study led by Garvan Institute in collaboration with a biotech firm called Redx Pharma out of the UK and (2) sulfasalazine, which is the investigational agent used in the study led by UNSW.
Both RXC004 and sulfasalazine have shown some promise in that according to UNSW’s press release they can “target the scar tissue around pancreatic cancers and prevent tumor growth in experimental models.”
RXC004 is actually a potent, selective, oral small molecule inhibitor of the enzyme, Porcupine, a key activator of Wnt ligands in the Wnt signaling pathway. Aberrant Wnt signaling contributors directly to tumor growth and plans an important role in immune resistance to treatment with immuno-oncology agents such as anti-PD-1 checkpoint inhibitors reports RedX Pharma based in the UK.
This investigational product is selected in research with patients with tumors that have high Wnt ligand dependency, such as tumors with mutations in the RNF43 gene and fusions in the RSPO gene family. Thus this novel therapy can directly target the tumor and also introduce an immune-enhancing impact.
Now in Phase 1 clinical trial data is expected sometime in the first half of 2021.
Sulfasalazine is called Azulfidine and is used to treat rheumatoid arthritis, ulcerative colitis and Crohn’s disease. Taken orally, it is considered by some as a first line treatment for rheumatoid arthritis. Part of the family of disease-modifying antirheumatic drugs (DMARDs) researchers are not fully clear as to how it works but have proposed mechanisms of action. Researchers from University of British Columbia a decade ago suggested its potential use targeting pancreatic cancer.
Principal Investigator Point of View
Professor Phoebe Phillips shared, “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 the basic scientific findings previously supported by NHMRC and PanKind (the Australian Pancreatic Cancer Foundation) into the clinical setting.”
While when addressing the novel therapeutics in the MoST-P program investigator and Associate Professor Marina Pajic with the Garvan Institute told UNSW press: “The two pancreatic cancer sub-studies aim to tackle what is currently a critical barrier to existing treatments: the scar tissue barriers around pancreatic tumors.” Dr. Pajic continued, “Our approach in this trial is a real step towards personalized medicine and pancreatic cancer, involving co-targeting of the cancer genome and specific signals from the stroma targeting.”
On the importance of this collaboration, professor Goldstein shared, “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.”
∙ David Thomas, Professor, UNSW
∙ Marina Pajic, PhD, Garvan Institute
∙ Paul Timpson, PhD, Garvan Institute
∙ Katrin Sjoquist, BSc(Med) MBBS MClinT (R) FRACP, University of Sydney
∙ Lorraine Chantrill, BSc MBBS FRACP PhD, NSW Health District
∙ Anthony Gill, MBBS FRCPA FFsc FRCPA MD, NSH Health
Call to Action: We need more powerful treatments to keep those battling pancreatic cancer alive longer. TrialSite applauds this Australian group and will monitor for updates. Sign up for the newsletter to keep updated.