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, the London Regional Cancer Program, Kingston General Hospital, and the Ottawa Hospital. In the near future, the Juravinski Cancer Centre in Hamilton will open to recruiting patients as well.

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.

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.

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.

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.

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.

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.

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