Patients undergoing FoundationOne liquid CDx while tissued-based NGS panel is in progress or reported within 4 weeks of enrollment

Patients undergoing no additional testing while tissue-based NGS panel is in progress or reported within 4 weeks of enrolment

Patients undergoing FoundationOne liquid CDx if standard tissue based NGS oncopanel testing identifies no somatic tier 1 variant of strong clinical significance

FoundationOne liquid CDx

Quality of life questionnaires

Cheryl Ho, MD

Shira Sabag, PhD

Jason Koleong, RN

The current standard of care for molecular characterization of tumors is tissue based next generation sequencing (NGS) panel. Liquid biopsies (ie blood) are of increasing interest and have been implemented as a diagnostic tool in some countries. This study compares tissue based and liquid based testing to evaluate the detection rate and cost consequence of using this new tool in BC.

Part A - Simultaneous - Patients will be randomized 1:1 to FoundationOne liquid CDx or no additional testing simultaneously at initiation of request for standard based tissue based next generation sequencing (NGS) panel testing. The objective of Part A is to evaluate the cost-consequence of the liquid ctDNA biopsy technology, FoundationOne liquid CDx, for first line molecular characterization of advanced colorectal cancer, melanoma, non small cell lung cancer (NSCLC), ovarian cancer, prostate cancer and triple negative breast cancer with simultaneous molecular characterization by tissue based NGS panel

Part B - Sequential - Patients will undergo standard tissue based NGS panel testing and if there are no somatic tier 1 variant of strong clinical significance identified the patients will then be eligible for FoundationOne liquid CDx. The objective of Part B is to determine the benefit of a sequential approach with molecular characterization by tissue based NGS panel testing followed by liquid based FoundationOne liquid CDx for patients who do not have an actionable tissue based oncogenic driver, across British Columbia.

The development and access to next generation sequencing (NGS) technologies on tumour tissue and blood allows the ability to profile the genomic landscape of the tumour within reasonable turn-around times and costs. The promise of precision oncology is the ability to 'match the right drug to the right patient at the right time'. Despite considerable excitement at the prospect of genome-informed therapy to improve oncologic outcomes, there has been little empirical assessment of its benefit from an overall population perspective and its true impact on cancer care delivery in 'real-world' scenarios.

While the enthusiasm for liquid biopsies has increased, the understanding of the cost implications lags behind. We propose to assess the true clinical impact on both individual patients and on a population-based cancer system of precision oncology via ctDNA analyses in metastatic solid tumors in a real-world scenario.

PRecision Oncology Evidence Development in Cancer Treatment - Liquid

PRecision Oncology Evidence Development in Cancer Treatment - Liquid AKA the Real World Clinical Utility of ctDNA Analysis for Decision Making and Access to Precision Therapy for Advanced Cancer Patients in BC: The RAPTor Sub-study

To compare health resource utilization of tissue based NGS panel alone, versus NGS panel and FoundationOne liquid CDx measured in Canadian dollars

To evaluate the ability of FoundationOne liquid CDx to detect actionable mutations that were not identified on the tissue based NGS oncopanel.

To evaluate the health resource utilization of tissue based NGS panel alone, versus panel and FoundationOne liquid CDx measured in Canadian dollars

To evaluate the clinical utility of tissue based NGS oncopanel +/- FoundationOne liquid CDx as measured by concordance/discordance of findings and subsequent treatment

To assess the impact of FoundationOne liquid CDx on the diagnostic patient pathway by comparing the number of patients who require repeat biopsies for molecular characterization.

To compare the quality of life impact of FoundationOne liquid CDx using the validated instrument, EuroQol 5 Dimension (EQ5D) (Scale of 0-100 where 0 is worst health and 100 is best health)

To evaluate the clinical utility of tissue based NGS oncopanel followed by FoundationOne liquid CDx as measured by concordance/discordance of findings and subsequent treatment

To determine the proportion of tissue based NGS oncopanel completed for which results are not available due to insufficient tissue. To be calculated by assessing number of patients with insufficient tissue for molecular characterization over the number of patients who have molecular characterization performed

Roche Pharma AG

British Columbia Cancer Agency

Neoplasms

All Conditions

Musculoskeletal Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Osteosarcoma

Sarcoma

Soft Tissue Neoplasms

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Bone Neoplasms

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

Bone Diseases

Soft Tissue Sarcoma

Ewing Sarcoma

Neuroepithelioma

This study involves collection of blood samples at pre-specified time points as well as collection of information about this disease.

For each timepoint, submit two tubes of blood (17 mL total or a little more than 3 teaspoons) per standard ctDNA workflow

This study involves collection of blood samples at pre-specified time points as well as collection of information about this disease.

For each timepoint, submit two tubes of blood (17 mL total or a little more than 3 teaspoons) to a commercial testing laboratory called Foundation Medicine and one tube of blood (10 mL or 2 teaspoons) to standard ctDNA workflow

a FoundationOne liquid biopsy test kit will be sent to the laboratory of the subject's treating center, in addition to the paired cell stabilizing tube from the primary center

FoundationOne Liquid CDx

David S. Shulman, MD

Edwin Choy, MD

David Shulman, MD

Pricilla Merriam, MD

David S Shulman, MD

Kris Ann Schultz

Kris Ann Schultz, MD

Brian Turpin, MD

Bhuvana Setty, MD

Rochelle Bagatell, MD

Bradley DeNardo, MD

Michael Bishop, MD

Avanthi Shah, MD

Luke Maese, MD

Doug Hawkins, MD

This is a prospective multicenter biomarker study evaluating the prognostic impact of ctDNA detection at diagnosis in patients with Ewing sarcoma or osteosarcoma.

The purpose of this study is to evaluate whether ctDNA in the blood can provide information about the chances of Ewing sarcoma or osteosarcoma coming back after treatment. This research study is evaluating a new advanced laboratory test to detect small pieces of tumor genes in the peripheral blood known as circulating tumor DNA (ctDNA).

Part A : During this part of the research study (Part A) participants will be asked to provide blood samples at pre-defined times. These blood samples may help find specific genetic alterations commonly seen in Ewing sarcoma or osteosarcoma that may allow investigators to learn more about the uses of ctDNA. The results of the ctDNA analysis will not be returned to participants.

Approximately 90 patients will take part in this study across multiple centers.

Part B: This research study is evaluating new advanced laboratory tests to detect small pieces of tumor genes in the peripheral blood known as circulating tumor DNA (ctDNA). Part B of the research study, which focuses on ctDNA tests that can be returned to providers and patients with Ewing sarcoma. This part of the study will allow comparison of commercial ctDNA testing from Foundation Medicine to our research testing. It is expected that about 60 people with Ewing sarcoma will take part in Part B of this research study.

The sponsor of this protocol is Dana-Farber Cancer Institute and is providing funding for the study. Additional funding for this study is provided by the Conquer Cancer Foundation of the American Society of Clinical Oncology, Alex's Lemonade Stand Foundation, Boston Children's Hospital Office of Faculty Development, the Friends of Dana-Farber Cancer Institute, The Harvard Catalyst Program, and the Spada Pediatric Sarcoma Foundation

Liquid Biopsy in Ewing Sarcoma and Osteosarcoma as a Prognostic And Response Diagnostic: LEOPARD

Liquid Biopsy in Ewing Sarcoma and Osteosarcoma as a Prognostic And Response Diagnostic: The LEOPARD Study

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
PRecision Oncology Evidence Development in Cancer Treatment - Liquid	NCT05057234	Cancer	FoundationOne l... Quality of life...	18 Years -	British Columbia Cancer Agency
Liquid Biopsy in Ewing Sarcoma and Osteosarcoma as a Prognostic And Response Diagnostic: LEOPARD	NCT06068075	Ewing Sarcoma Ewing Sarcoma o... Ewing Sarcoma o... Peripheral Prim... Peripheral Prim... Peripheral Prim... High-grade Oste...	FoundationOne L...	12 Months - 50 Years	Dana-Farber Cancer Institute

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