OICR created the Clinical Translation Pathway (CTP) to accelerate translational cancer research so that precise, impactful and cost-effective treatments can benefit cancer patients.
The CTP supports practice-changing research in biomarkers, diagnostics and therapeutics that will advance early detection and intervention research and have a clear path to the clinic and clinical impact. It focuses on primary-diagnosed cancer or early recurrent cancers. The Pathway is fueled by innovations emerging from OICR-supported research and from research originating from across the province. Importantly, it supports implementation science approaches aimed at the adoption of findings into clinical practice.
The CTP funding streams are:
- Pre-Clinical Acceleration Team Awards (Pre-CATA): Support pre-clinical projects with a clear path to the clinic, with a focus on development of biomarkers, diagnostics, and therapeutics.
- Clinical Acceleration Team Awards (CATA): Support early phase (I-II), prospective, biomarker-rich trials for clinical validation of biomarkers, diagnostics, and therapeutics.
- Window of Opportunity (WOO) Trials: Support pre-surgical trials focused on biomarker analysis characterizing the mechanism of action of single or combination agents that modulate the anti-tumour immune response in newly diagnosed, treatment naïve patients.
- Innovation to Implementation Supplement (I2IS): Move OICR research/innovations from experimental phase towards health policy or health system implementation.
Dr. Glenn Bauman – Lawson Health Research Institute
New imaging techniques provide insights into localizing and tracking prostate cancer in men throughout diagnosis and treatment. This project will investigate the value of tracking imaging changes before and after treatment to predict longer-term cancer control. An imaging scan will be done prior to treatment and then be used for planning radiation treatments to deliver more intensive doses to spots of cancer within the prostate and/or regional lymph nodes identified by imaging. Baseline and post-treatment changes in multi-modal imaging biomarker measurements will be analyzed for correlation with five-year disease-free survival to identify potential non-invasive imaging biomarkers that may serve as early indicators of long term disease control.
Dr. Jane Bayani – Ontario Institute for Cancer Research
Active surveillance in prostate cancer requires multiple invasive biopsies which can have serious side effects, yet this surveillance is only helpful in about 10 percent of cases. Nevertheless, it continues to be required because there is not a better option. To address the need for improve testing at diagnosis, Dr. Bayani’s team will use a molecular test called “PRONTO” for use in tissue biopsy specimens, which was developed through a collaborative multi-institutional program led by OICR (Adaptive Oncology) researchers including Dr. Bayani. This new study will adapt the PRONTO signatures for use in urine by testing matched biopsies and urine from men with early prostate cancer. Validation in this cohort will provide the necessary level of evidence to integrate non-invasive urine profiling at the time of diagnosis with targeted MRI biopsy and tissue risk profiling, through active surveillance using sequential urine samples as a practice-changing clinical management strategy for early prostate cancer
Dr. Tobias Berg – McMaster University
Acute myeloid leukemia (AML) is an aggressive cancer of the blood system. Despite advances in treatment, only 21 percent of patients survive more than five years. If an allogeneic stem cell transplant can be performed, the five-year survival rate improves to 30-50 per cent. Despite this treatment’s effectiveness, many patients relapse. In these patients, AML returns aggressively and is associated with shorter survival. The LSD1 enzyme (protein) is a promising new target for treating AML. Blocking this enzyme can change the way malignant blood cells behave, destroy malignant stem cells, and even activate an immune response against malignant cells. This study investigates a drug that blocks LSD1’s functions in the cell to see if it can prevent relapse after stem cell transplant. The Berg team will also study the features in leukemia that may be used as biomarkers and may allow them to identify patient groups who will benefit from this approach.
Dr. Scott Bratman – University Health Network
Human papilloma virus (HPV) is a causative agent for several cancer types. Despite aggressive treatment, some patients experience recurrence. Measurement of circulating tumour DNA (ctDNA) following therapy can reveal molecular residual disease (MRD) prior to recurrence. This provides an opportunity to direct intensified treatment to patients who are likely to relapse. This multidisciplinary team of investigators developed two platforms – multiplexed digital PCR and HPV- sequencing – that enable ultrasensitive analysis of HPV ctDNA. In this study, they will evaluate the performance of these platforms for detection of molecular residual disease in HPV+ cancers following (i) definitive treatment with chemoradiotherapy and (ii) de-escalated treatment.
Dr. Scott Bratman – University Health Network
Circulating tumour DNA (ctDNA) has emerged as a potentially important tool to detect molecular residual disease (MRD) after standard treatment in patients with curative cancers. Locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC) is a type of cancer suited to the study of what is known as MRD interception, since many patients relapse or their cancer recurs despite aggressive therapy. MERIDIAN is a randomized Phase II clinical trial to assess the efficacy of a new immunotherapy regimen in LA-HNSCC patients with detectable ctDNA-based MRD following standard therapy. The research team hypothesizes that the experimental treatment will cause ctDNA clearance and improved survival. If successful, MERIDIAN will contribute to more personalized treatment strategies that are desperately needed for patients with this challenging disease.
Dr. David Cescon – University Health Network
HER2+ breast cancer is an aggressive subtype, for which very effective therapies have been developed over the last two decades, dramatically improving outcomes. However, metastatic disease remains incurable, and continued efforts to prevent recurrence in people at high risk are necessary. New drugs have been shown to be effective at treating (but not curing) patients with metastatic (Stage 4) disease. Using optimal therapies earlier, before a patient’s disease recurs, may provide a cure; but because of the high cost and extreme toxicity of treatment, these interventions are used only for those who might benefit. New technologies can detect minute quantities of DNA from tumour cells in the blood with a liquid biopsy. By detecting these markers of impending recurrence, patients may be identified for treatment intensification and the effects of treatment may be directly measured by repeated non-invasive blood testing. In this clinical trial, the team will identify patients with early-stage HER2+ breast cancer who have evidence of residual disease and measure the effect of adding an additional, proven anti-HER2+ targeted agent to their treatment regimen. This work will provide key insights into the potential utility of these powerful new diagnostic technologies and targeted therapies to guide the most precisely-delivered treatment for high risk HER2+ breast cancer, and inform the future development of a treatment to identify and eliminate lethal metastatic recurrence for patients with potentially curable breast cancer.
Dr. Eric Chen – University Health Network
Colorectal cancer is the third most commonly diagnosed cancer in Canada and is a leading cause of cancer-related death. The usual treatment for patients with advanced disease is palliative chemotherapy, with an average survival of 30 months. Recent research findings indicate that some cancer cells can survive chemotherapy by becoming less active. This Phase II study will investigate whether combining a drug called hydroxychloroquine with standard of care chemotherapy can overcome this resistance and improve patient outcomes.
Dr. John Dick – University Health Network
Dr. Dick’s team has uncovered a new framework to understand the unique cellular hierarchy of each of the acute myeloid leukemia (AML) patients in their study cohort of more than 1,000 people. This new hierarchy-based modeling integrates mutational drivers with leukemia stem cell properties and is highly predictive of both patient survival and relapse. Using machine learning, they have developed specific hierarchy classifiers that accurately predict response to a wide range of targeted therapies. This study will refine these new AML classifications for future clinical trials. This new hierarchy classification offers the potential to guide treatment decisions and inform the design of drug combinations in a new way for AML.
Dr. Marc de Perrot – University Health Network
Mesothelioma is caused by professional or environmental exposure to asbestos. Even if detected at an early stage, about half of the people with this diagnosis die from their tumour within 1.5 years. In previous studies, the de Perrot team demonstrated that it is feasible and efficient to treat mesothelioma by combining a short course of radiation targeting the whole tumour followed by surgery one week later. Using this concept, they observed that patients could be freed from their tumour for an average of up to four years in early-stage mesothelioma. They now plan to refine the process by modulating the immune system to optimize the long-term benefit of this approach and potentially achieve a cure in early-stage mesothelioma.
Dr. Richard Kim – Lawson Health Research Institute
Modern chemotherapy often includes 5-fluorouracil and capecitabine. These chemotherapies are effective and widely prescribed for the treatment of various cancers. However, patients are at high risk for experiencing severe, sometimes life-threatening toxicity during treatment with these chemotherapy medications. Genetic deficiency in the enzyme dihydropyrimidine dehydrogenase (DPD, gene name DPYD) has been recognized as an important cause of this toxicity. However, we now know that common genetic variations in DPYD identify only a subset of patients at risk for severe toxicity during this chemotherapy. To further enable individualized and precise dosing and treatment options for 5-fluorouracil and capecitabine chemotherapy, the Kim team has created a custom targeted NextGen (NGS) DNA sequencing panel that is capable of rapid identification of patient-specific rare genetic variants in DPYD. They are also able to measure circulating microRNA that regulate DPYD, from patient-derived blood samples. The team plans to demonstrate that integration of targeted NGS coupled with microRNA measurement from patient-derived blood samples prior to chemotherapy will result in more precise 5-fluorouracil and capecitabine dosing and less toxicity for patients.
Dr. Natasha Leighl – University Health Network
Lung cancer is the leading cause of cancer and cancer deaths in Ontario and globally. Although 40 per cent of people with lung cancer have early-stage disease that can be removed with surgery, the risk of returning cancer and death remains high. Currently, we do not have the tools to know who is at risk of their cancer returning. Recently, blood tests called liquid biopsies have been developed that can detect evidence of persisting cancer cells by finding genetic material from cancer, called circulating tumour DNA (ctDNA) in blood. ctDNA levels can also be followed over time or monitored for changes. If a person has high levels of ctDNA detected after surgery, or their ctDNA levels start to rise, giving them protective treatment to kill any remaining cancer cells may help cure them. This study is looking at the use of ctDNA levels to identify lung cancer patients after surgery at high risk of cancer returning. For those found to be at high risk, the team will offer cancer drug therapy to try and prevent recurrence. In the future, this means doctors could use a liquid biopsy blood test to decide who is at high risk of recurrence after surgery, and who needs treatment with additional drug therapy after surgery to prevent recurrence and increase the chance of cure.
Dr. Stephanie Lheureux – University Health Network
Ovarian cancer is a difficult disease to treat because most women are diagnosed late due to unspecific symptoms. Once diagnosed, surgery and chemotherapy are standard treatment for ovarian cancer and while first responses to these are good, most women will see the return of their cancer. Recent discoveries have shown that certain genes can help ovarian cancer grow when they are damaged. Drugs known as PARP inhibitors, that work by preventing cancer cells from repairing damage, have been shown to be effective at keeping cancer at bay after women have responded to chemotherapy when they are newly diagnosed and when cancer has returned. However, no treatment has been established after cancer comes back or continues to grow following the use of PARP inhibitors. This project will provide an innovative approach to guide treatment in real-time based on mechanisms of resistance identified in each patient.
Dr. Mitchell Sabloff – The Ottawa Hospital
Acute myeloid leukemia (AML) is an aggressive cancer of the bone marrow. Standard of care treatment uses intensive chemotherapy. However, 10 per cent of patients will not survive the effects of the chemotherapy and many will not respond to treatment or will relapse. A personalized or precision medicine strategy that identifies unresponsive AML patients and offers them a targeted drug to make them responsive to standard treatments would greatly improve their survival. The Sabloff team has identified functional biomarkers which may identify those patients who will and will not respond to standard treatments, as well as drugs that may make unresponsive patients respond better to standard treatments. In this study, they will finish developing and validating a clinical diagnostic biomarker test analyzing AML patient bone marrow samples to determine whether these biomarkers can identify AML patients who do or do not respond to standard treatments. They will also determine whether the biomarkers identify unresponsive AML patients who may benefit from the experimental targeted drug.
Dr. Ana Spreafico – University Health Network
Pembrolizumab is a drug that targets the immune system by “lifting its brakes” and allowing its own immune cells to attack cancer. Pembrolizumab is a first choice in patients with advanced head and neck cancer whose tumour has returned or spread after initial therapy. Unfortunately, only a limited number of patients benefit from this drug and the reasons why are not completely understood. A link between bacteria present in the human gut (the intestinal microbiome) and immunity has been well demonstrated. The composition of the intestinal microbiome may induce anticancer response and increase immunotherapy effectiveness. Stool of patients who respond to immunotherapy harbour more “good bacteria” than non-responders. Modifying the intestinal microbiome composition to boost the immune system is an innovative and promising area of research. Microbial Ecosystem Therapeutics (MET)4 is a group of 30 bacterial species selected for their abilities to stimulate immunotherapy response. MET4 was designed to increase “good bacteria” in the gut. This research team demonstrated that MET4 combined with immunotherapy is safe and more of these bacteria is found in people that receive it. This study compares MET4 with pembrolizumab versus pembrolizumab alone in advanced head and neck cancer patients to evaluate if the MET4 and pembrolizumab combination can result in: 1) tumour shrinkage; 2) increased “good bacteria” in the patients’ intestines; 3) increased length of life, while maintaining quality of life, and; 4) discovery of markers of response to the treatment via tumour, blood, oral swab and stool samples analysis.
Dr. Martin Yaffe – Sunnybrook Research Institute
There is solid evidence that earlier detection of breast cancer through the routine screening of women ages 40 – 74 contributes to a reduction in deaths due to breast cancer. But mammography, the most widely used screening technique, loses accuracy in women with very dense breasts where signs of disease may be masked or create false alarms for breast cancer. If we can identify those women for whom the potential for cancer masking is highest, they can be offered supplemental or alternative screening with imaging tools whose performance will not be impaired by dense tissue. The Yaffe team has developed an automatic computer technique based on image analysis and artificial intelligence to determine which women should be offered alternative screening. In this study, they will complete the technique’s optimization and test its performance in allowing a precision medicine strategy for breast cancer detection. They will evaluate the effect of different precision screening regimens on reducing missed cancers and on the type of additional cancers found. They will determine the best balance between the number of women who would be offered supplemental screening and the number of previously missed cancers that would be picked up.
Dr. Gang Zheng – University Health Network
Porphysomes are a novel nanoparticle-based agent developed at the Princess Margaret Cancer Centre. After injection into the body, Porphysome particles accumulate at high concentrations within cancer cells over 24-48 hours. Upon uptake in tumours and metastases, clinicians can image Porphysomes using PET-imaging and high-resolution optical imaging for the purposes of treatment planning and image-guided cancer surgery. Additionally, when laser light is shone on tumours with Porphysomes, the tumours are destroyed with either heat or chemicals. These light-based therapies permit precise cancer cell ablation/destruction without needing to remove healthy tissues. This multidisciplinary team of scientists and clinicians have tested the safety and effectiveness of Porphysomes in different pre-clinical tumour. The primary goal of this Phase 1 study is to confirm Porphysome safety in patients with an increasing dose. The secondary goal is to demonstrate Porphysome image-guided light-based treatments in each cancer site using site-specific protocols addressing clinical needs for improved surgical precision and tumour ablation.
CTP is part of OICR’s Clinical Translation (CT) research theme, which is the translational engine of the Institute, advancing discoveries into clinical testing. It supports the advancement of discoveries through early clinical validation, partnering with patients, industry and the health system for downstream development and implementation.