The IL23 sarcoma clinical study

The Background

When Cooper was in the hospital fighting for his life in Australia, the 18-year-old was extremely curious about why there were no new treatments. He asked his doctors’ many questions his dad Colin Brading noted.  Cooper passed due to the bone cancer, tragically, but his family set up a foundation to help search for a cure to the disease—it was what Cooper wanted. His life force lives on in his foundation which will persist from now onward to help others that were in his position.

Enter Interleukin-23 (IL23)

Researchers at Garvan Institute of Medical Research uncovered that the immune molecule is key to the growth of the tumor and targeting it in studies successfully shrank cancer in mice reported 9 News in Australia. Immunotherapies targeting IL23 represent an important push in the fight against autoimmune diseases such as arthritis, inflammatory bowel disease, and the skin condition psoriasis.  Professor David Thomas with Garvan Cancer Research and Director of The Kinghorn Cancer Centre noted: “When we blocked IL23 or knocked it out in the mouse in this particular case, we stopped tumors from development.”

Planned Sarcoma Study Powered by the Spirit of Cooper Rice-Brading

The Cooper Rice-Brading foundation is helping to pay for clinical research along with the Garvan Institute of Medical Research to explore existing IL23 therapies for this form of bone cancer. Funds inbound will go towards clinical trials which will commence before the second half of 2020 reports 9 News. Professor Thomas noted, “We hope to treat up to 32 people with advanced, incurable sarcomas.”

The Cooper Rice-Brading Foundation

For those that want to contribute to keeping Cooper’s vision alive, they can follow the link to the Cooper Rice-Brading Foundation and contribute so that we can be certain that this important clinical trial will occur.  Brading’s dad stated, “it is Cooper’s vision becoming a reality.” See the link for the donation page.

The Garvan Institute of Medical Research

Garvan Institute of Medical Research is a leading, multi-disciplinary biomedical research institute in Darlinghurst, Sydney. With some of the brightest minds and best technologies on the planet, they like to look at the big picture of health and disease.

They were founded in 1963 by the Sisters of Charity as a research department of St. Vincent’s Hospital. Now one of Australia’s largest medical research institutions with approximately 750 scientists, students and support staff.

Major focus areas for investigational research include cancer, diabetes, osteoporosis, Alzheimer’s disease, Parkinson’s disease as well as other autoimmune disorders and asthma. They specialize in genetic and molecular technologies and emphasize collaborative research.

In 2014 the institute became part of an elite group that has the ability to sequence the human genome at a base cost below $1,000 each ($1,000 genome) when it purchased the next generation of genome sequencing technology, capable of sequencing 350 genomes a week. 

Long tumour correlation

LTD Changes Correlate With OS in Localised High-Risk Soft Tissue Sarcoma

June 20th 2020
OncLive have last week reported a percentage change in longest tumor diameter of patients with localised high-risk soft tissue sarcoma, treated with neoadjuvant chemotherapy, were found to correlate with overall survival.

A percentage change in longest tumour diameter (LTD) of patients with localised high-risk soft tissue sarcoma (STS) who were treated with neoadjuvant chemotherapy was found to correlate with overall survival (OS), according to updated results from a phase 3 trial presented at the 2020 ASCO Virtual Scientific Program.1

Of the 325 patients who enrolled on the study and were determined to be evaluable for response, 181 received neoadjuvant chemotherapy; 92 of those patients received standard chemotherapy comprised of an Epirubicin and Ifosfamide, while 89 received histology-driven chemotherapy.2 The other 144 patients received concurrent chemoradiotherapy and were excluded from the analysis. RECIST data were available for a total of 176 patients, 90 of whom were in the standard arm and 86 of whom were in the investigational arm.

Results demonstrated a significant link between changes in LTD and OS rate in patients with STS. Specifically, the correlation between survival and response was observed in the overall patient population as well as within the standard and investigative cohorts. Patients in the overall population who experienced any amount of reduction in LTD (n = 101) were noted as having a better prognosis than those who experienced no changes (n = 28) or had an increase in LTD (n = 52). Percentage changes in LTD were also associated with OS within the standard (log-rank, = .023) and the investigative arms (log-rank, = .053), as well; however, different patterns were observed.

For the analysis, investigators set out to determine the prognostic relevance of percentage changes in LTD in patients with STS who were treated with neoadjuvant chemotherapy. In the trial, patients with localised high-risk STS, either of the extremities or the trunk walls, and who had been diagnosed with myxoid liposarcoma, leiomyosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumour, or undifferentiated pleomorphic sarcoma were randomised to receive either 3 cycles of the neoadjuvant standard regimen or the histology-tailored regimen.

Notably, patients with myxofibrosarcoma, pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma, or unclassified spindle cell sarcoma were prospectively registered and received treatment with the standard regimen.

Percentage changes in LTD were found by evaluating these levels at baseline and after 3 cycles of treatment with either regimen before surgery. Investigators evaluated OS in both groups post-surgery through the use of Kaplan-Meier estimates and log-rank tests. Then, they looked for cutoffs that would be allow them to determine prognosis with either an increase or reduction in LTD by applying a proposed change-point method.

Further results from an unplanned analysis within the study were also reported. For this effort, investigators applied cut-point methodology to establish non-significant optimal cutoffs with regard to tumour reduction (20%, = .14), as well as progression (25%, = .47). Although the investigators were able to demonstrate a reasonable survival pattern through these cutoffs, a validation study of the proposed cutoffs is necessary in order to thoroughly evaluate them.

“In our study, RECIST V. 1.1 and any [percent] reduction in LTD of patients treated with neoadjuvant chemotherapy for localised high-risk STS correlated with the outcome,” the investigators wrote. “A [percent]variation cutoff both in increase and decrease in LTD able to predict the outcome could be identified only for the whole patients population. ”

Reference

  1. Stacchiotti S, Morosi C, Braglia L, et al. Prognostic role of % changes in longest tumour diameter (LTD) in localised high-risk soft tissue sarcoma (STS) treated with neoadjuvant chemotherapy in a randomised clinical trial. J Clin Oncol. 10.1200/JCO.2020.38.15_suppl.11558
  2. Localised high-risk soft tissue sarcomas of the extremities and trunk wall in adults: an integrating approach comprising standard vs histotype-tailored neoadjuvant chemotherapy. ClinicalTrials.gov. Updated May 13, 2019. Accessed June 19, 2020. https://clinicaltrials.gov/ct2/show/NCT01710176?term=NCT01710176&draw=2&rank=1

ANZSA Scientific Conference 2019

The Australia New Zealand Sarcoma Association annual scientific meeting was held in Canberra on 11th and 12th of October, bringing together a collection of the most stellar medical and scientific minds, all working toward a cure for sarcoma.

The conference showcased the ground breaking developments in research which will and in some cases are, of benefit to sarcoma patients globally, thus providing untold hope for the future.

It was an enormous privilege for our own Mitchell Rice-Brading to open the conference, with a passionate and heartfelt speech which was central to his own experiences of losing his younger brother Cooper, to sarcoma.

 

Transcript below:

 

My name is Mitchell Rice-Brading, and I am the brother of the young man whose name our Foundation proudly bears.

I would like to begin today by extending my deepest gratitude to ANZSA, and in particular, Dr Denise Caruso, for having me speak this morning, and I would like to impress the great privilege that I personally attach to the opportunity.

I’d also like to acknowledge the work that goes into both organising an event of this magnitude, and to making the effort to attend. As a recently graduated uni student, I am currently working 20 hours a week as a bartender.  I have just returned from the World Cup in Japan, and has another trip planned to Thailand at the end of the month, I can empathise with all of you in the room. We’ve all made sacrifices to be here today.

On a more serious note, my family and I find ourselves as incidental members of the greater sarcoma community.  It was unplanned, and unexpected. Unlike us, most of you in this room have chosen to devote your time working to improve the plight of those touched by a sarcoma diagnosis. We are humbled by the selflessness of choosing such a career path.

We have come to realise, that with the heartache and devastation that is a sarcoma diagnosis, it has also become the driving force for what ultimately brings us here today, motivated to instigate critical and positive change.

The gravity of losing my brother to this cancer is something I find difficult to articulate.  I can never see a day when the senseless loss of Cooper’s life will be something I can rationalise. Tragically, my brother became one of the many real faces of sarcoma, and now I am all too aware of what sarcoma represents, and why conferences such as this, are yet another crucial step forward.

Because, for all the scientific complexities, there is one unavoidable constant that follows a sarcoma diagnosis –  pure devastation.

Walking the road beside Cooper, I felt helpless. Sleepless nights pondering the future; The ever- present guilt because I was not the one afflicted; and the unwavering desire to say and do the right things to provide comfort, but ultimately feeling like nothing was ever enough.

And then there was the soul-crushing final act, helplessly witnessing the brother I grew up with, regress into a mere shell of his larger than life self, when treatment options were exhausted. Sadly, this an all too regular outcome for young sarcoma patients.

Nonetheless, my family were left with a choice: Sit on our hands and do nothing, or perpetuate Cooper’s memory and his vision, by joining with the remarkable group before me, and make a contribution no matter how small.

It is of note that as recently as three and a half years ago, when Cooper was first diagnosed with osteosarcoma, treatment options were severely limited. This, of course, was no reflection on his stellar medical team – it is simply the way it was.

Similarly, a body of up to date, reliable, and user friendly information for patients and their families proved impossible to source. In our family, and I suspect in others, we introduced one policy: No Internet. The information that presented itself after one google search was astoundingly outdated, and generally soul-crushing for a recently diagnosed 17 year old boy.

Compounding this, was the fact adolescent patients were, and are, routinely treated in adult facilities, some barely past the age of 14. I dare say it won’t shock you to know, the needs of a teenage boy are vastly different to those of a 70 year old man.

Just over three years later, and the positive change is palpable. The emergence of future adolescent sarcoma centres, such as the one proposed for Chris O’Brien Lifehouse; dedicated sarcoma nurses helping patients through the medical minefield; imminent clinical trials for a number of sarcoma sub-types; cutting edge genomic sequencing programmes and trials; peer reviewed studies published in significant medical journals – the list goes on…

This, together with the highly credible and relevant information available on the new ANZSA website, has indeed removed a lot of angst out of those first weeks post-diagnosis. The change is visible and there for all of us to see, and is largely attributed to the persistent work of a number of those in the room today.

We are truly privileged to be working with some of the most distinguished clinicians and scientific researchers in this field. Then there are those who are driven by tragedy, who work tirelessly for change, and have created the most outstanding legacies to the loved ones they have lost, through fundraising and awareness campaigns.

I look around this room, and it is difficult not to be humbled and somewhat moved.  You inspire us as the relative new kids on the block, to adopt the patience, resilience and determination you have all shown over many years. They say Rome wasn’t built in a day, and nor will sarcoma be cured in a day, and it is these qualities in each of us, which will ultimately lead to critical advancements.

I don’t necessarily have what it takes to be a medical oncologist, nor have the deep biological knowledge required for meaningful research. But all of us in the room today are fighting sarcoma as a team, and all players in a team have a role.  At the Cooper Rice-Brading Foundation, our role is clear: to assist in facilitating your work, and to support you in future initiatives. And when we look at the progress we’ve already made, it is simply difficult not to be inspired, and to push through on the difficult days.

From all of us at CRBF, we extend our deepest gratitude to each of you for the outstanding work you continue to accomplish in this field, and for openly accepting us as a small part of this stellar team.

All of us here today are aspiring to make sarcoma history, and we’re not giving in.

 

 

 

Sarcoma awareness campaign launch

Press here to view full interview

https://www.9now.com.au/today/2019/clip-cjrsgj2hy00000gmpt4vndnxv

Wednesday 6 February saw the launch of the CRBF national sarcoma awareness video on the Nine Network, Today Extra.

The interview was superbly crafted, with Coop’s dear friends Michael ‘Wippa’ Wipfli and Peter Overton leading the segment with their in depth knowledge on the plight of sarcoma patients, and the cancer itself.  Peter and Wippa were faultless in their delivery, and their humanisation of the story behind the Foundation.  At the core of what we do, are the faces of sarcoma, and they are the same faces that drive us to instigate change by providing funding and awareness for this cancer.  It is therefore critical we do not lose sight of those for whom we work.

Seasoned professionals, David Campbell and Richard Wilkins were flawless as hosts, and we thank them for the very respectful way the segment was navigated.  Sarcoma is an intensely serious topic, and can be a very tricky in an interview environment.  It proved to be no hurdle for either of these polished presenters.

Finally, we want to express our gratitude to the powerhouse duo behind the scenes, Today Extra producers, Liz Adam, and Blake Dale, who had thoroughly researched the segment, and directed the piece in such a respectful and factual manner.

This important initiative would not be possible without each of these outstanding individuals who shone the spotlight on sarcoma and the inherent issues faced by patients, clinicians, families and loved ones.

Once more we find ourselves searching for words to express our gratitude to this fabulous foursome.

CRBF Sarcoma Awareness Campaign

The production of this awareness campaign has been a labour of love based on Cooper’s vision to ask the generous public figures and celebrities in his life, to join him in creating a national awareness programme for sarcoma.

The rationale behind this was simple.  He felt no-one would listen to a “pimply faced teenager with sarcoma”, but they may listen to this high profile collective, and in doing so lives could be saved.  Early diagnosis saves lives, and awareness of this cancer is paramount to improving survival outcomes.

Sadly Coop did not live to see what his friends have produced, however we know he would be humbled by the finished result, as the passion for cause is evident from all those involved.

We would like to extend heartfelt thanks to our celebrities in no particular order Peter Overton, Jessica Rowe, Michael ‘Wippa’ Wipfli, Mia Freedman, Peter FitzSimons, Callum Mills, Jimmy Barnes and Paul Roos, for helping us shine a light on sarcoma in our national awareness campaign.  

We extend a very warm thank you to our young sarcoma survivors, Imogen Atkins and Charlii Croese for the courage and bravery they have shown in participating in this campaign. We remain in awe of your resilience and determination.

Special thanks to Rudimental and songwriter John Newman, for allowing us to use’ Not Giving In’ as our soundtrack without fees, and to the amazing and ever dependable John Watson,  Founder, Eleven:  A Music Company, and manager to Jimmy Barnes, for facilitating the process.

Finally we thank our stellar and highly talented producers, James Tindale and Kristy Everett for their outstanding work, their patience and direction, together with the ever generous Michael Cordell for the loan of equipment, George Tyler for his creativity and guidance when filming our celebrities, and to Claire Bonic for her behind the scenes help throughout filming.

Sarcoma included in new Aus data …

Cancer Australia has released initial National Data on Australian paediatric cancer stages at diagnosis, including the rare and aggressive Sarcoma cancers.

This data covers sixteen major cancer types, which represent approximately three-quarters of all childhood cancers diagnosed in Australia. To see more please see ASSG’s press release or visit

https://childrenscancer.canceraustralia.gov.au/stage-diagnosis-data

Biosceptre’s Phase 1 Clinical Trial


On the 21st of February Biosceptre’s proposed Phase I clinical trial for BIL06v (anti-cancer vaccine) was granted conditional approval by the Bellberry Ethics committee. Biosceptre is now proceeding to take BIL06v into a Phase I trial in late Q2 or early Q3 2018.

Biosceptre has high confidence in the safety of BIL06v, in part as a result of pre-clinical studies and compassionate access patients treated in Australia under the TGA’s Special Access Scheme.

The planned clinical trial will recruit between 20 and 30 patients from a basket of late stage cancers and seeks to confirm safety, tolerability and immunogenicity of BIL06v.  The planned clinical trial will also seek to identify early indications of efficacy in humans.

CEO Gavin Currie said “Having recently closed entry to our Series A fund raising round, we are pleased that this fully funded clinical trial, building on significant preclinical data, has been conditionally approved.  We consider that a successful clinical trial, our first for a systemic therapeutic product targeting nfP2X7, will provide further validation of nfP2X7. We are hopeful for first patient recruitment in Q2 2018.”

 

Read more about the very promising developments regarding the BIL06v anti-cancer vaccine and nfP2X.

http://www.biosceptre.com/technology/

Garvan Institute – Sarcoma Research


Using whole-genome sequencing to research deeply into our DNA has led to the discovery that all disease is linked to genetic mutations so that instead of trying to treat disease symptoms, we can now target the mutations causing them. This is personalised medicine.  Read more about the outstanding work of the Garvan Institute, providing untold hope for sarcoma patients.

https://www.garvan.org.au/research/diseases/sarcoma/research

Therapeutic target for Ewing sarcoma


The sarcoma research group of the Bellvitge Biomedical Research Institute (IDIBELL), led by Dr. Òscar Martínez-Tirado, has identified a potential new therapeutic target for Ewing sarcoma, the second most frequent bone cancer in children and adolescents, and a tumour known by its aggressiveness and tendency to metastasise.

https://www.news-medical.net/news/20180405/Researchers-discover-potential-new-therapeutic-target-for-Ewing-sarcoma.aspx