September 20, 2019
Ottawa cancer researchers and clinicians embrace the window of opportunity between a cancer diagnosis and treatment with a coordinated approach to clinical research
The time between a patient’s cancer diagnosis and their surgery presents a valuable “window of opportunity” to evaluate new treatment strategies. Short-term clinical trials during this period – also known as window of opportunity trials, window trials or phase 0 trials – can help researchers gain insights into the effects and the efficacy of a new potential treatment. Dr. Angel Arnaout at The Ottawa Hospital is putting window trials into practice.
“There are many nervous and anxious moments between diagnosis and their surgery but patients have limited options during this time,” says Arnaout.
“We saw an opportunity in this window of time to take action. We saw that we could help support patients who are waiting for surgery, while helping future patients through accelerating clinical research.”Dr. Angel Arnaout
Arnaout, a surgical oncologist who specializes in breast cancers, assembled a cross-disciplinary team of medical oncologists, pathologists and other clinical research specialists at The Ottawa Hospital to strategically design and implement this new approach. They would collectively establish common priorities, decide on which interventions would be tested and work to streamline the patient’s journey throughout the process.
Together, the team was motivated by the mutual benefits of all stakeholders involved. Namely, window trials can provide patients an opportunity to contribute and engage with cancer research while potentially improving the state of a patient’s disease. Meanwhile, these trials could ultimately expedite drug development by improving the understanding of a potential drug early in its development.
The team launched their first study in 2014, which found that patients were exceptionally eager to participate, and since then, launched and completed three additional window trials.
The first was a breast cancer trial on presurgical hormone therapy that helped establish the capacity and infrastructure for enrolling patients, organizing the investigations and giving patients short-term therapies. The second tested a potential cancer-fighting agent, chloroquine, and found that it had no effect on stopping breast cancer proliferation. The third trial debunked the idea that vitamin D – even at very high doses – can slow down the growth of breast cancer.
“These studies didn’t uncover a new therapy, but they did help us answer important questions that patients have, like ‘Will taking vitamin D help?’” says Arnaout. “These types of studies also provide a relatively quick method to test whether we should continue research into a particular avenue.”
The group at The Ottawa Hospital has recently teamed up with researchers from OICR to initiate a new breast cancer window-of-opportunity study to examine biomarkers of efficacy and resistance for another new drug candidate. The trial is planned to begin recruitment by mid-fall this year.*
Despite the benefits of these trials, Arnaout adds, it is still important to reduce unnecessary delays between diagnosis and surgery. Arnaout continues to minimize these delays at The Ottawa Hospital.
“We try our best to reduce wait times, but if patients have to wait – we can try to help them in the meantime while accelerating breast cancer research.”
*This new trial is co-led by Dr. John Hilton from The Ottawa Hospital and Dr. John Bartlett from OICR. Co-investigators include Drs. Laszlo Radvanyi, Melanie Spears, Arif Ali Awan, Mark Clemons, Greg Pond and Angel Arnaout.
July 30, 2019
Genome Canada, Ontario Institute for Cancer Research and Thermo Fisher Scientific to focus on pancreatic, prostate and breast cancer
CARLSBAD, Calif. – (July 30, 2019) – Genome Canada, the Ontario Institute for Cancer Research (OICR) and Thermo Fisher Scientific are collaborating to develop a complete solution of targeted next generation sequencing (NGS) assays and analysis software designed to more effectively assess – and eventually improve management of – pancreatic, prostate and breast cancer.
The $6 million, three-year initiative aims to standardize advanced molecular profiling in these disease areas and make the assays commercially available globally. Focusing on rapid genomic diagnostics in pancreatic cancer and targeting treatment in breast and prostate cancers, the partnership builds on previous clinical research between OICR and Thermo Fisher and will inform development of three assays that will be utilized to stratify patients in clinical trials in Ontario and other jurisdictions.
“By supporting research and clinical trials, Genome Canada is helping to put more of Ontario’s innovative cancer diagnostics research into clinical use,” said Dr. John Bartlett, program director, diagnostic development at OICR. “This project has the potential to springboard advanced next-generation sequencing to routine clinical use in Ontario and across Canada.”
Breast and prostate cancer are among the most common types of cancer in Canada, and the country’s five-year net survival rate for pancreatic cancer is only 8 percent. However, there is clear evidence that patient outcomes can be improved with NGS-based testing strategies. A recent U.S. health economics study has shown that advanced cancer patients who received treatment based on NGS testing results experienced double the length of progression-free survival without increasing health care costs.1
While some solutions analyze only DNA sequences, the new targeted NGS assays will provide comprehensive genomic profiles by simultaneously assessing DNA and expression signatures from RNA to provide significantly more insight into driver mutations. The OICR/Thermo Fisher team will leverage this advantage by supplementing the new assays with unique DNA/RNA stratification biomarkers – specific to pancreatic, prostate and breast cancer – previously qualified by OICR translational researchers.
The collaboration is partly funded with a grant from Genome Canada through the Genomic Applications Partnership Program (GAPP). Genome Canada will contribute $2 million, the highest possible level of funding support, with the balance split between OICR and Thermo Fisher, which will cover development costs and validation activities.
Previous research collaborations led by OICR and Thermo Fisher are already well on their way to impacting cancer treatment in the future. Of particular note is a 2016 study designed to identify mutations and copy number variation changes in breast cancer, and clinical research utilizing the Oncomine Comprehensive Assay, which also supports both the National Cancer Institute’s Adult and Pediatric MATCH trials in the United States.
“OICR is a leader in clinical research, with extensive clinical trials in progress to improve care for patients with pancreatic, prostate and breast cancer,” said Jeff Smith, global lead of NGS precision medicine initiatives, clinical NGS and oncology for Thermo Fisher Scientific. “When OICR approached our team with the idea for this project, we saw it as another exciting for opportunity to bring Thermo Fisher’s proven Ion Torrent technology to clinical laboratories across Canada and to contribute to future improvement of patient care.”
1 “A Retrospective Analysis of Precision Medicine Outcomes in Patients With Advanced Cancer Reveals Improved Progression- Free Survival Without Increased Health Care Costs,” Journal of Oncology Practice, Vol 13, Issue 2, February 2017
March 15, 2019
Expert researchers find shorter treatment cycles may reduce risk of breast cancer returning
Researchers have found that the dosage and interval of chemotherapy treatments have a significant impact on some breast cancer patients’ survival. For a very small minority of patients the difference of a week between chemotherapy treatments could mean the difference between life and death – and researchers are working to identify exactly who those patients are.
Over the last few decades, breast cancer clinical trials have investigated the way in which patients receive and respond to different chemotherapy dosing regimens. Some have tested if a shorter – but more intense – two-week treatment cycle is more effective than the standard three-week cycle. These trials, however, are often limited in size and do not have the statistical power to detect a difference in response to treatment.
Researchers from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) have recently performed a meta-analysis across 26 breast cancer trials to help clarify this dosing dilemma. As reported in The Lancet, they found that more intense dosing regimens were associated with a decreased risk of death from breast cancer and a decreased risk that the disease will return in some patients.
“As chemotherapy kills tumour cells, the residual – or remaining – cancer cells have more room to grow and tend to grow faster,” says Dr. John Bartlett, Program Director of Diagnostic Development at OICR and member of the EBCTCG Steering Committee. “These trials hypothesized that a more intense dosing regimen would give tumour cells essentially less room to grow. With the results of the EBCTCG overview study, we can say with confidence that a two-week treatment schedule will help to prevent death in a small portion of patients.”
The analysis found that approximately one in 50 women benefited from more intense dosing.
“The challenge now is to determine exactly which patients can benefit from intense dosing and which patients would not,” says Bartlett.
“If we can do so, we can prevent deaths due to breast cancer for some, while minimizing the negative side effects of intense chemotherapy for others.”
The ECBTCG is continuing to investigate dosing intensity in common breast cancer subtypes in parallel with researchers who are looking to find the biological basis of these differing responses to treatment.
“We’re in an era of de-escalation where we’re heavily invested in reducing overtreatment,” Bartlett says. “But this work helps us move towards an era of biologically rational treatment recommendations, one where breast cancer patients get the treatment they need at the right time and in the right way.”
February 12, 2019
Sometimes the simpler, the better: bringing personalized treatment selection for bladder cancer closer to the clinic
Pathology experts review challenges and opportunities in treatment selection for muscle-invasive bladder cancer (MIBC), propose traditional pathology method to achieve same results as molecular profiling at lower cost
Research has shown that some types of bladder cancer respond well to treatment and other types are resistant, yet molecular subtyping, which can help better define a patient’s cancer and direct them to a more targeted treatment, is not performed in the clinic. This means that patients are often treated with a one-size-fits-all approach. Despite recent research progress, the movement of MIBC subtyping to the clinic has stagnated.Continue reading – Sometimes the simpler, the better: bringing personalized treatment selection for bladder cancer closer to the clinic
October 24, 2018
Research team finds aggressive breast cancers are less frequent than previously thought, and less aggressive breast cancers need more of our attention.
Different subtypes of breast cancer respond to treatment differently and require different treatment approaches. Understanding the distribution of these subtypes and their respective clinical outcomes allows researchers to better understand the disease and identify key research priorities that may have been previously overlooked.
September 24, 2018
OICR takes part in international multicentre study to standardize promising breast cancer digital pathology test
The Ki67 immunohistochemistry assay is a test that can help evaluate the aggressiveness of breast tumours, predict disease outcomes, monitor cancer progression and identify patients who are more likely to respond to a given therapy. Despite its potential to help patients with breast cancer, the analysis of Ki67 has not been widely adopted in the clinic, mostly due to the lack of standardization across laboratories.
June 4, 2018
Current HER2 tests help predict which breast cancer patients will respond to HER2-targeted therapies, but sometimes these tests provide unclear results. An Expert Panel of pathologists and cancer researchers, including Dr. John Bartlett from OICR, recently published revised clinical practice guidelines for HER2 testing in breast cancer to help improve clarity of HER2 test results.
January 25, 2018
The Canadian Data Integration Centre receives new funding to help cancer researchers translate findings to patients
Toronto (January 25, 2018) – The Canadian Data Integration Centre (CDIC) has received $6.4 million in funding from Genome Canada to help the research community translate the biological insights gained from genomics research into tangible improvements for cancer patients.
CDIC is a “one-stop shop” service delivery platform for cancer researchers, helping streamline research by providing coordinated expertise on a broad range of services, including data integration, genomics, pathology, biospecimen handling and advanced sequencing technologies. It is an international leader in genomics, bioinformatics and translational research, supporting some of the world’s largest programs in genomic data analysis, genomic and clinical data hosting, cancer data analyses and access, and the development of algorithms for advanced sequencing technology.
January 12, 2018
Endocrine therapy uses hormone antagonists to greatly reduce the risk of disease recurrence in women with early-stage, estrogen-receptor (ER) positive breast cancer. However, the treatment can come with severe side effects. Around 30 per cent of women stop taking the therapy after three years largely due to these negative impacts. Usually patients receive the hormone therapy for five years following initial treatment (e.g., chemotherapy, surgery), but it can also be taken longer-term. A central question facing patients and clinicians is how to balance, in their decision making, the side effects of long-term treatment with the potential reduction in recurrence risk. In short, they want to know: ‘is it worth it?’
May 3, 2017
The advent of genomic sequencing and targeted therapies has opened the door to new ways of diagnosing and treating cancer. The Ontario-wide Cancer Targeted Nucleic Acid Evaluation (OCTANE) program is a new, province-wide initiative supported by OICR that will allow more patients to benefit from these innovations while also helping to advance cancer research in Ontario.
April 13, 2017
Breast cancer is the most common form of cancer amongst women in Canada and worldwide, but despite its prevalence, a group of researchers believes that it should often be treated as a rare disease. Doing so would change clinical approaches and improve treatment for patients.
November 23, 2016
On November 16 OICR and the Ontario Molecular Pathology Research Network (OMPRN) joined other organizations around the world celebrating International Pathology Day.