Ongoing Studies

OCTANE: Ontario-wide Cancer Targeted Nucleic acid Evaluation

Eligible cancer types: Non-small cell lung, Colorectal, Malignant melanoma, Breast, Gynecological, Genitourinary, Pancreatobiliary, Gastrointestinal, Head and Neck, Unknown primary, Rare cancers

Significant progress has been made in the treatment of cancer through the use of targeted therapies, but what works for one patient may not work for another. Certain drugs are now being developed that target specific molecules in the body that are believed to be a part of the disease. Biomarkers are specific characteristics of the cancer that may aid in predicting sensitivity or resistance to treatment as well as provide prognostic information.

This study is an Ontario-wide initiative, and will collect archival tumour samples (previously collected biopsy or surgical tumour samples) to provide biomarker data about a patient’s cancer. This information may help physicians in guiding the use of approved treatments that may benefit their patient as well as identifying which clinical trials of new drug treatments may be most appropriate for the patient in the future. This study will also be used to develop a province wide registry of targeted gene sequencing testing that will be made available to cancer researchers. Additional tumour tissue and blood samples collected from all study participants will be stored in a biobank at the Ontario Institute for Cancer Research for future research. Additionally, data from this study will be linked to other health care data bases to collect information about the health care patients receive, which may include medical tests, clinic visits, or procedures both before and after participating in the study. Having this additional information about a patient’s health may provide new insights into cancer and its treatment

This study is currently open to patients who are being treated at the Princess Margaret Cancer Centre and the Ottawa Hospital.

INSIGHT: Integrative Sequencing In Germline and Hereditary Tumours

Eligible patients: multiple primary malignancies, families with a strong family history of cancer suggestive of a hereditary cancer syndrome, young individuals with cancer (10 years earlier than the age of onset of sporadic cases) and no identified gene mutation, rare cancer histologies

Hereditary cancer accounts for approximately 5-10% of all cancer occurrences, and are usually characterized by a family pattern of similar types of cancer, early onset cancer, multiple cancers in the same individual and rare cancer histology.

The objective of this study is to uncover contributors to inherited cancer through genome-wide germline analysis of individuals and families with or at risk of a hereditary cancer syndrome and to clarify novel mechanisms of tumorigenesis in hereditary cancer patients. Furthermore, this study is proposed to determine the utility of whole genome sequencing of the germline in identifying hereditary disorders.

HEARTBEAT-OV: Halting Early Advancement of Residual disease by Treatment with BEvacizumab and ATezolizumab in OVarian Cancer

Eligible cancer types: TP53-mutant high grade serous or high grade endometroid ovarian, fallopian tube, primary peritoneal cancer. Patients must also be receiving, or have had received platinum-based chemotherapy for recurrent disease.

Epithelial Ovarian cancer is diagnosed in more than 230,000 women worldwide each year. Despite multiple new approaches to treatment over the past 30 years, 5-year overall survival rates remain relatively unchanged with a 5-year overall survival of approximately 46%. As such, maintenance therapy post platinum based chemotherapy has been investigated with the aim of preventing or delaying disease relapse and the goal of improving overall survival.

The primary purpose of this study is to examine the association between the dynamic change in TP53 ctDNA levels and disease outcome by comparing baseline and 3-month samples in order to determine if increase in TP53 ctDNA level from baseline is associated with radiological disease progression. Further, this study aims to determine whether treatment can be effectively guided by TP53 circulating tumour DNA analysis.

LIBERATE: LIquid Biopsy Evaluation and Repository Development AT PrincEss Margaret

Eligible cancer types: Solid tumour, hematological malignancy , OR patients identified as high-risk for cancer based on hormonal/family history without known abnormality, patients identified as high-risk for cancer based on identified alteration in cancer predisposition gene.

Circulating cell-free nucleic acids (cfDNA) are non-invasive biomarkers that can provide diagnostic and prognostic information before cancer diagnosis, during cancer treatment, and at the time of disease progression. Scientists and Clinicians at Princess Margaret Cancer Centre are interested in incorporating the collection of liquid biopsies (peripheral blood) into research protocols in an effort to non-invasively assess tumour progression and response to treatment at multiple times during a patient’s disease course.

The purpose of this study is to develop an institution-wide liquid biopsy protocol in order to establish a common process for biobanking blood and corresponding tumour specimen for future research studies at Princess Margaret Cancer Centre.

IRIS: Immune Resistance Interrogation Study

Eligible cancer types: Any solid tumors who have progressed on immunotherapy as their most recent line of treatment.

Although there has been some success with the use of immunotherapy treatments specifically antibodies that block the programmed death 1 receptor (PD1/L1), most cancer patients either fail to respond (primary resistance) or respond initially but progress after a period of time (acquired resistance) when treated with immunotherapy agents. In recent years the use of immunotherapy (IO) treatments has increased significantly in clinics. However not all patients who receive IO treatments benefit from them. During this study, samples will be collected to understand if patients who have primary resistance versus acquired resistance to immunotherapy show different disease biology.

PM.1 CAPTUR: Canadian Profiling and Targeted Agent Utilization Trial

Eligible cancer types: Metastatic solid tumours, multiple myeloma, or B cell non-Hodgkin lymphoma (NHL - excluding chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) and hairy cell leukemia (HCL)).

This is a multi-centre, open-label, phase II basket trial, matching Canadian patients who have undergone molecular profiling and found to have tumour genetic variant(s), to appropriate targeted agents. Drug matches will be drawn from a list of commercially available anticancer agents, supplied by participating pharmaceutical partners.

The main purpose of this study is to evaluate the objective response rate of targeted drugs matched to pre-specified molecular aberrations within a tumor type with an “actionable” genomic variant known to be a target of a Health Canada-approved anticancer drug or to predict sensitivity to a Health Canada-approved anticancer drug.

BEAVER: Binimetinib and Encorafenib for the treatment of Advanced solid tumors with non-V600E BRAF mutations

Eligible cancer types: THistologically or cytologically-documented, locally-advanced, or metastatic solid malignancy that is incurable and has either (a) failed prior standard therapy, (b) for which no standard therapy exists, or (c) standard therapy is not considered appropriate by the patient and treating physician. In addition, malignancy must express one of several eligible BRAF alternations.

BRAF is among the most commonly mutated kinases in human cancer, particularly in melanoma, with 40-50% of tumors harboring an activating mutation in BRAF. BRAF is also frequently mutated in several other cancer types, such as: 10-70% of thyroid cancers (depending on the type), ~10% of colorectal cancers (CRC), and ~5% of non-small cell lung cancer (NSCLC). The primary purpose of this study is to evaluate the objective response rate (ORR) of binimetinib and encorafenib in the treatment of patients with advanced solid tumors expressing non-V600E BRAF mutations.

REFLECT: Prospective Evaluation of Freshly ImpLantEd Cancers in Mice to Test Drug Response in Matching Host

Eligible cancer types: Triple negative breast cancer, colorectal cancer, other select tumour types (at the discretion of the Principle Investigator)

Rapid advances in genomic characterization technologies have led to the implementation of profiling of patient tumour samples to identify “actionable mutations” (defined as alterations that predict or confer sensitivity or resistance to a drug). The goal of clinical sequencing is to identify potential treatment strategies based on individual tumour characteristics. An alternate approach that has been suggested to help guide the selection of therapy for individual patients is the application of in vivo drug testing in personalized patient-derived xenografts (pPDX). pPDX are laboratory models of an individual’s cancer grown and expanded in immunocompromised mice, which provides an opportunity to assess the impact of a variety of drugs on in vivo tumour growth.

The purpose of this study is to incorporate personalized PDX testing into an active clinical program of genomic profiling and drug matching currently underway at Princess Margaret Cancer Centre, and to assess the feasibility of prospective pPDX generation, drug sensitivity testing and data integration from (a) surgical samples following neoadjuvant chemotherapy and (b) biopsies or surgical resection of metastatic lesions.

GENIUS: Genomic Investigation of Unusual Responders

Eligible cancer types: Advanced breast, colorectal, non-small cell lung, gynecological, upper aerodigestive tract, pancreatobiliary, genitourinary, unknown primary, rare cancer and who have responded exceptionally well to a therapeutic drug or were expected to respond favourably to a drug but displayed a poor outcome.

The purpose of this study is to investigate tumors that respond abnormally well or poorly to therapeutic agents in an effort to understand the genetic basis of this response. Patients who have responded exceptionally well or exceptionally poorly to certain drugs will have archived tumor specimens molecularly profiled using whole genome/exome sequencing to try to determine if there is a genomic reason for such responses to these agents.

OCTANE 2.0: Ontario-wide Cancer Targeted Nucleic acid Evaluation

Eligible cancer types: Cutaneous melanoma (advanced/metastatic treated with ICI or Stage III treated with adjuvant PD-1 ICI), Non-small cell lung (advanced/metastatic treated with ICI or Stage III treated with chemoradiotherapy followed by adjuvant ICI), Sarcoma (translocation-associated or undergoing metastasectomy), Breast (Stage II/III ER- treated with neoadjuvant chemotherapy), Oligometastatic (Colorectal, Breast, Renal and NSCLC patients with 3-5 metastases treated with ablative radiotherapy), Colorectal (Stage III/IV undergoing primary tumor resection, and/or curative metastasectomy), Pancreatic (undergoing primary tumor resection, and/or neoadjuvant chemotherapy and/or radiotherapy prior to planned tumor resection).

The first phase of OCTANE has been successful through the development of a biospecimen repository and infrastructure for clinical and genomic data sharing. Stage 2 will build upon the first stage by longitudinally expanding biospecimen sampling and standard-of-care image collection to develop more accurate and robust prognostic and predictive markers of adaptive resistance and relapse.This study plans to open at the Princess Margaret Cancer Centre, Juravinski Cancer Centre, London Health Sciences Centre, The Ottawa Hospital, Kingston Health Sciences Centre, Sunnybrook Health Sciences Centre and Mount Sinai Hospital.

NIP IT!: Non-Invasive Artificial Intelligence-Based Platform Monitoring Program

Eligible cancer types: Head and Neck, Breast, Melanoma

Circulating tumor DNA (ctDNA) can be used to detect molecular residual disease (MRD) in patients who have undergone definitive treatment, but are at high risk of relapse. The detection of MRD, before clinical or radiological relapse, will allow for early cancer interception. The purpose of this study is to determine the utility of liquid biopsies and other non-invasive biomarkers in detection of MRD across tumor types. Specifically, patients at high risk of relapse will be monitored by analyzing their serial blood samples, stool and radiological images. The goal is to develop AI-based models to identify those who are at the highest risk of relapse.

MASST: Multi-Omic Assessment of Squamous Cell Cancers receiving Systemic Therapy

Eligible cancer types: Histological or cytological diagnosis of Squamous cell Cancer of the head and neck, esophagus or anal canal. In addition, patients must demonstrate radiologically confirmed recurrent or metastatic disease and be commencing on a new treatment at the time of enrollment.

This study will investigate the feasibility of performing ultra-deep sequencing of plasma derived circulating tumor DNA (ctDNA) for genomic assessment, in conjunction with epigenetic analysis, immune profiling and radiomic imaging signatures to explore the dynamic changes during management with systemic treatment. That is, the purpose of this study is to comprehensively characterize genomic and epigenetic features and changes associated with systemic treatment of recurrent/metastatic squamous cell cancers of the head & neck, esophagus and anal canal.

TUSCAN: Insight on the Use and Value of Genomic Analysis in Cancer Patients – A Pan-Canadian Survey of Oncologists and Patients

Eligible cancer types: Histologically-confirmed incurable metastatic solid tumour (excluding primary brain tumours), multiple myeloma or B cell non-Hodgkin lymphoma (excluding CLL, SLL, and HCL), for whom there is no standard treatment known to prolong life, or who has refused such treatment.

The purpose of this study is to evaluate the use and value of Next-Generation Sequencing (NGS) in cancer patients. The study will assess how Canadian oncologists use NGS tests to inform treatment plans, pre- and post- testing. Additionally, patients who are candidates for NGS will be surveyed to assess their view on precision medicine.

IO-KIN: Study of circulating tumor DNA (ctDNA) kinetics in immuno-oncology

Eligible cancer types: Recurrent, metastatic or advanced head and neck cancer.

Immune checkpoint blockade has emerged as an effective therapy in many different tumors, including metastatic head and neck squamous cancer (HNSCC). Early determination of response to immune checkpoint blockade could enable patients who are deriving clinical benefit to continue therapy while sparing others from unnecessary toxicities and cost. Therefore, non-invasive new biomarkers are needed to provide a better understanding and selection of patients who may benefit from these drugs.

This study aims to study the kinetics of ctDNA levels after the first dose of immune checkpoint inhibitor in patients with recurrent or metastatic head and neck cancer. This is an important study to understand the optimal timing for ctDNA quantitation for future studies in immunotherapy, though further validation would be needed in other tumor types. IO-KIN will provide preliminary data of the role and feasibility of intense ctDNA monitoring treated with IO drugs, specifically anti-PD-1 antibodies.

COMPARISON: Comprehensive GenoMic Profiling of ColorectAl CanceR Patients with Isolated Liver MetaStases to Understand RespOnse and ResistaNce to Cancer Therapy

Eligible cancer types: Colorectal cancer with isolated liver metastasis planned for hepatic metastasectomy OR previous treatment with surgery for primary colorectal cancer with or without having received chemotherapy after surgery and are now diagnosed with isolated liver metastasis with plans for hepatic metastasectomy

According to the Canadian Cancer Society, Colorectal Cancer (CRC) is the second leading cause of cancer mortality in Canada, with 9200 deaths per year. Within the context of colorectal cancer and isolated liver metastasis, genomic features that predict the development of subsequent liver metastases and increase the risk of recurrence after surgery are not yet defined. The purpose of this study is to perform genomic and epigenetic profiling of primary colorectal tumours, recurrent tumours, and liver metastases to determine and understand the biological mechanisms vital to chemotherapy resistance and disease recurrence, as well as identify potential therapeutic targets.

NET-SEQ: Prospective Comprehensive Molecular Profiling In Neuroendocrine Tumors

Eligible cancer types: Neuroendocrine carcinomas

Molecular profiling of fresh tissue samples from neuroendocrine carcinomas using genomic and transcriptomic technologies to discover genetic alterations that may be useful in determining what treatments may be beneficial to the patient’s response or resistance to specific targeted agents, such as mTOR pathway inhibitors. Patients will also have archival paraffin-embedded tumour tissue profiled.

HPV-SEQ: Genomic Analysis of HPV-related Lung Metastases from Head and Neck Cancers

Eligible cancer types: HPV-related head and neck and lung neoplasms

Sequencing of archived tumor samples from HPV-related lung metastases in patients with squamous cell carcinoma of the head and neck (HNSCC) to identify driver mutations that might be responsible for the metastatic pattern and evaluate concordance of genotyping information for patients with HPV-related HNSCC with HPV-positive lung lesions.

COMPACT: Community Oncology Molecular Profiling in Advanced Cancers Trial

Eligible cancer types: Advanced breast, colorectal, non-small cell lung, gynecological, upper aerodigestive tract, pancreatobiliary, genitourinary, unknown primary, rare cancer

In November 2012, COMPACT was opened as a parallel arm of the IMPACT study to make molecular profiling available to patients who are receiving their cancer treatment at other Greater Toronto Area hospitals. These patients are referred to the Princess Margaret by their community medical oncologists for participation in this study. A rotating roster of three staff oncologists (Drs. Lillian Siu, Dr. Philippe Bedard, and Dr. Albiruni Razak) assess and consent patients who have been referred to the Princess Margaret for molecular profiling. COMPACT patients remain under the care of their referring physicians. All COMPACT molecular profiling reports are sent to the treating medical oncologist with additional information regarding what is known about detected mutation(s) and available clinical trials with matched targeted therapies when standard of care therapy is no longer effective.

I-IMPACT: Immunoprofiling in IMPACT study

Eligible cancer types: Gynecological, pancreatic, locally advanced squamous cell cancer of the head and neck, any tumor type receiving immune therapies as standard therapy or enrolled on investigational clinical trials

This study looks to characterize a patient’s immune contexture as a potential method to more accurately define prognosis and possibly even predict responses to immunotherapies.

IMPACT: Integrated Molecular Profiling in Advanced Cancers Trial

Eligible cancer types: Breast, Colorectal, Non-small cell lung, Gynecological, Upper Aerodigestive Tract, Pancreatobiliary, Genitourinary, Unknown Primary, Rare Cancers

In March 2012, IMPACT was launched as a pilot study at the Princess Margaret Cancer Centre. This study involves the molecular profiling of archival paraffin-embedded tumour tissue for Princess Margaret patients with advanced breast, colorectal, non-small cell lung, gynecological, upper aerodigestive tract, pancreatobiliary, genitourinary, unknown primary, and rare cancers, as well as patients with melanoma and phase I trial patients who are candidates for systemic therapy. The primary objective of IMPACT is to provide the treating clinician with molecular profiling information for their patients that may be used to guide treatment and/or clinical trials with matched targeted therapies in the future. Results of molecular profiling are included in patient’s medical records. Through large molecular profiling initiatives such as IMPACT, the goal is that new knowledge can be gained about the genetic alterations or changes in cancers which affect their clinical outcomes and responses to drug therapies.

OCTOPUS: Feasibility Clinical Study of Circulating Plasma DNA Analysis in Advanced Solid Tumor Patients

Eligible cancer types: Advanced breast, colorectal, non-small cell lung, gynecological, upper aerodigestive tract, pancreatobiliary, genitourinary, unknown primary, rare cancer

This study tests the feasibility of detecting genomic alterations in pieces of tumor DNA (circulating plasma DNA) and tumor cells (circulating tumor cells) in the blood, using different technologies and methods.

MATCH: A Feasibility Study of Genomic Profiling Methods and Timing of Sample Collection to Evaluate Clonal Evolution and Tumor Heterogeneity

Eligible cancer types: : Metastatic colorectal, breast, gynecological, melanoma cancers

The MATCH study looks at the feasibility of collecting small volume fresh tissue samples via a core needle biopsy and/or fine needle aspiration for the purposes of molecular profiling. Serial sampling and profiling of tumor samples over time also provides insight on the clonal evolution and intratumor heterogeneity of molecular alterations in cancer. All MATCH patients will also be enrolled in the IMPACT study, and results from the molecular profiling of the archival tissue will be included in the patient’s medical record.

SPECIAL: Selection Pressure and Evolution Induced by Immune Checkpoint Inhibitors And Other ImmunoLogic Therapies

Eligible cancer types: Head and Neck and melanoma

Tumours arise from a single cell that evolves clonally over time. During tumour progression, replication stress causes genomic instability and produces diverse clones of cancer cells that could have different survival potentials under various selection pressures such as chemotherapy and immunotherapy. This diversity within a tumour is likely to determine primary drug resistance. Any type of anticancer treatment applies selection pressure and the “fittest clone or clones” of cancer cells that are resistant to the treatment will be selected for tumour progression (according to Darwin’s evolution principles). Therefore, it is necessary to study tumour evolution during a patient’s therapeutic journey to understand the mechanisms that mediate resistance.

The purpose of this feasibility study is to assess tumour evolution under the selection pressure induced by Immune Checkpoint Inhibitors (ICIs) in patients with advanced solid tumours by performing genomic profiling of serial tumours and circulating tumour DNA (ctDNA). ICIs have recently emerged as a promising therapeutic for patients with solid tumours, but there is no published study that describes how tumours evolve under this selection pressure