Tissue vs Liquid Biopsy for Cancer Diagnosis

(PREDiCTl Trial)

Overseen By Shira Sabag, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: British Columbia Cancer Agency

Disqualifiers: Unavailable for follow up, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two methods for cancer detection: tissue biopsy and liquid biopsy (blood test). The researchers aim to determine which method is more effective at detecting cancer and whether one is more cost-effective. Participants are divided into groups to test these methods either simultaneously or sequentially. Suitable candidates have metastatic cancer (cancer that has spread) and are already undergoing tissue-based tests. The liquid biopsy method under evaluation is called FoundationOne Liquid CDx. As an unphased trial, this study provides participants the opportunity to contribute to innovative cancer detection research.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. It is best to consult with the trial coordinators or your doctor for guidance.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this method is safe for cancer diagnosis?

Research has shown that FoundationOne Liquid CDx is a well-researched and FDA-approved blood test. It examines over 300 genes, providing a comprehensive liquid biopsy option. FDA approval confirms its safety for patients in various situations.

Studies indicate that the risks associated with this test are low. Its approval and widespread use suggest that most patients tolerate the test well. Although no medical procedure is entirely risk-free, the established safety of FoundationOne Liquid CDx makes it suitable for many individuals. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the potential of using liquid biopsies as a method for cancer diagnosis. Unlike the traditional tissue biopsies, which require invasive procedures to collect samples from tumors, liquid biopsies use a simple blood draw to detect cancer markers. This method could significantly speed up diagnosis, reduce patient discomfort, and provide a more comprehensive view of the cancer by capturing tumor DNA circulating in the bloodstream. By comparing tissue and liquid biopsy results, researchers hope to determine if liquid biopsies can be as effective or even superior in identifying critical genetic mutations, paving the way for more personalized and timely cancer treatment strategies.

What evidence suggests that this trial's treatments could be effective for cancer diagnosis?

Research shows that FoundationOne Liquid CDx, one of the investigational tests in this trial, accurately identifies important genetic changes in cancer using just a blood sample. Studies have demonstrated its effectiveness in detecting key genetic alterations, which can guide treatment choices. The FDA has approved the test to assist doctors in selecting the right therapies based on the tumor's genetic profile. Evidence indicates that this liquid biopsy can identify important mutations that traditional tissue tests might miss, making it a promising tool for diagnosing cancer and planning treatment. Participants in this trial may undergo FoundationOne Liquid CDx testing either simultaneously with or sequentially after standard tissue-based testing. ^{1 3 6 7 8}

Who Is on the Research Team?

Cheryl Ho, MD

Principal Investigator

BC Cancer

Are You a Good Fit for This Trial?

This trial is for adults over 18 with metastatic cancer, treated at BC Cancer, who are undergoing or have recently undergone tissue-based molecular characterization. It's not suitable for those unwilling to consider systemic treatments or unavailable for follow-up.

Inclusion Criteria

My cancer is being tested using advanced genetic tests on a tissue sample.

Part A - Simultaneous: Tissue based NGS panel requested or reported within 4 weeks of enrolment, Patients receiving treatment at BC Cancer

I am older than 18 years.

Exclusion Criteria

I am not open to considering treatments that affect my whole body.

Patients not available for follow up

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Simultaneous Testing

Patients are randomized to either FoundationOne liquid CDx or no additional testing while undergoing standard tissue-based NGS panel testing

4 weeks

1 visit (in-person)

Sequential Testing

Patients undergo standard tissue-based NGS panel testing, followed by FoundationOne liquid CDx if no actionable mutations are found

24 months

Follow-up

Participants are monitored for safety and effectiveness after testing

24 months

What Are the Treatments Tested in This Trial?

Interventions

• FoundationOne liquid CDx

Trial Overview The study compares traditional tissue-based next-generation sequencing (NGS) panel testing with a new liquid biopsy method using blood samples to see how well each detects cancer mutations and assesses the cost implications of the new technology in British Columbia.

How Is the Trial Designed?

Group I: Simultaneous - no additional testing Experimental Treatment 1 Intervention

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

Group II: Simultaneous - FoundationOne liquid CDx Experimental Treatment 2 Interventions

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

Group III: Sequential - FoundationOne liquid CDx Experimental Treatment 2 Interventions

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 is already approved in United States, European Union for the following indications:

Approved in United States as FoundationOne Liquid CDx for:

• Non-small cell lung cancer (NSCLC)
• Breast cancer
• Colorectal cancer
• Ovarian cancer
• Melanoma

Approved in European Union as FoundationOne Liquid CDx for:

• Non-small cell lung cancer (NSCLC)
• Breast cancer
• Colorectal cancer
• Ovarian cancer

Who Is Running the Clinical Trial?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

Roche Pharma AG

Industry Sponsor

Trials

413

Recruited

430,000+

Dr. Thomas Schinecker

Roche Pharma AG

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Dr. Levi Garraway

Roche Pharma AG

Chief Medical Officer since 2019

MD from University of California, San Francisco

Published Research Related to This Trial

A study involving 45 pediatric patients with relapsing or refractory solid tumors demonstrated that liquid biopsy using Foundation One® Liquid CDx is a feasible method for molecular profiling, successfully identifying targetable mutations in 25 samples.

Out of the patients analyzed, 6 received treatment based on liquid biopsy results, leading to one patient achieving stable disease for eight months, highlighting the potential of liquid biopsies in guiding treatment decisions in pediatric oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood-Derived Liquid Biopsies Using Foundation One® Liquid CDx for Children and Adolescents with High-Risk Malignancies: A Monocentric Experience. Cahn, F., Revon-Riviere, G., Min, V., et al.[2022]

In a study of 130 Japanese patients with advanced solid tumors, clinical sequencing identified actionable gene alterations in 87.7% of cases, suggesting a high potential for personalized treatment options.

Despite the promising results, only 22.3% of patients received treatment based on these genetic findings, indicating that while clinical sequencing is useful, there are still challenges in implementing these insights into clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of comprehensive genomic profiling in Japan: Result of PROFILE-F study. Aoyagi, Y., Kano, Y., Tohyama, K., et al.[2022]

Liquid biopsies (LB) have the potential to guide personalized treatment and monitor disease in colorectal cancer (CRC) patients, but their clinical use is not fully realized, as shown in a study of 86 CRC patients at two German cancer centers from 2017 to 2021.

In this study, there was a significant divergence (39%) in RAS status between tissue-based and liquid-based diagnostics, highlighting the need for standardization and further research to improve the implementation of LB in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liquid Biopsy in Colorectal Cancer: Quo Vadis? Implementation of Liquid Biopsies in Routine Clinical Patient Care in Two German Comprehensive Cancer Centers. Fischer, LE., Stintzing, S., Heinemann, V., et al.[2022]

Liquid biopsies, which analyze components like circulating tumor cells and circulating free DNA from body fluids, offer a less invasive alternative to traditional tissue biopsies for cancer diagnosis and monitoring.

These innovative methods can provide valuable biomarkers for early cancer detection, prognosis, and treatment prediction, although each technology has its own advantages and limitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Different Facets of Liquid Biopsy: A Kaleidoscopic View. Eslami-S, Z., Cortés-Hernández, LE., Cayrefourcq, L., et al.[2022]

Liquid biopsy, which analyzes circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), is a promising tool in personalized medicine for monitoring cancer evolution and treatment response in real time.

CTC and ctDNA analyses have significant implications for cancer prognosis, detection of minimal residual disease, treatment selection, and even early cancer diagnosis, highlighting their growing importance in clinical trials and cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of liquid biopsy in the management of cancer patients. Markou, A., Tzanikou, E., Lianidou, E.[2022]

Liquid biopsy is a promising and less invasive method for analyzing solid tumors by using blood, saliva, or urine to detect biomarkers, allowing for real-time assessment of cancer characteristics.

This technique, particularly through the analysis of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), has the potential to improve personalized medicine and monitor treatment response, although further standardization and validation are needed for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell-Free DNA in the Liquid Biopsy Context: Role and Differences Between ctDNA and CTC Marker in Cancer Management. Fici, P.[2019]

In a study of 43 Japanese patients with advanced solid tumors, the FoundationOne CDx test successfully identified actionable gene mutations in 96% of cases, indicating its potential clinical utility in guiding treatment decisions.

Despite the high detection rate of mutations, only 15% of patients received treatments corresponding to their identified mutations, primarily due to disease progression and reduced performance status, highlighting challenges in translating genomic findings into clinical action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Utility of Comprehensive Genome Profiling Using FoundationOne CDx in Japanese Population(PROFILE-F Study)]. Kumaki, Y., Takahashi, K., Mitsumura, T., et al.[2020]

The FoundationOne®Liquid CDx assay, a cfDNA-based genomic profiling tool, has been validated through over 7,500 tests, demonstrating high accuracy in detecting genomic alterations across more than 30 cancer types, with a positive agreement of 96.3% compared to other methods.

This assay shows a very low false positive rate of 0.013% and high reproducibility (99.59%), making it a reliable option for identifying patients who may benefit from precision therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and analytical validation of FoundationOne Liquid CDx, a novel 324-Gene cfDNA-based comprehensive genomic profiling assay for cancers of solid tumor origin. Woodhouse, R., Li, M., Hughes, J., et al.[2020]

Liquid biopsies can detect and monitor cancers earlier than traditional methods, which could lead to better outcomes for patients.

This innovative approach allows for the characterization of tumors, potentially improving personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Applications of liquid biopsies for cancer. Mattox, AK., Bettegowda, C., Zhou, S., et al.[2020]

Liquid biopsies, which analyze biofluids like blood or urine for tumor-related molecules, are emerging as valuable tools in cancer management, potentially serving as alternatives to traditional tissue biopsies.

This review highlights three key methods of liquid biopsy—circulating tumor cells, extracellular vesicles, and circulating tumor DNA—demonstrating their diagnostic and prognostic potential in assessing cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liquid Biopsy in Solid Malignancy. Scarlotta, M., Simsek, C., Kim, AK.[2023]

Liquid biopsy demonstrated a very high concordance rate with conventional tissue biopsy, accurately detecting all genetic mutations found in tissue samples without any false negatives, indicating its reliability as a diagnostic tool.

In a study of 29 lung cancer patients, liquid biopsy identified 26 mutations, with the ALK mutation being the most prevalent in 96.6% of patients, suggesting that liquid biopsy could be particularly useful when tissue samples are limited or unavailable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary Experience of Liquid Biopsy in Lung Cancer Compared to Conventional Assessment: Light and Shadows. Montella, M., Ciani, G., Granata, V., et al.[2023]

Liquid biopsy (LB) is a promising method for cancer detection and monitoring, as it analyzes circulating tumor cells and nucleic acids in biofluids, overcoming the limitations of traditional tissue biopsies.

LB has shown effectiveness across various cancer types, including lung, colorectal, and breast cancers, by identifying biomarkers that can help predict disease progression and tailor treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Perspective and Translational Oncology of Liquid Biopsy. Fernández-Lázaro, D., Hernández, JLG., García, AC., et al.[2020]

Liquid biopsy is a noninvasive method that can detect biomarkers related to tumor development and progression, offering significant advantages over traditional solid biopsies, especially when solid biopsies are not feasible.

This review highlights the use of circulating tumor cells, circulating free DNA, and exosomes in liquid biopsies for diagnosing cancer, monitoring recurrence, assessing prognosis, and planning medication, showcasing their potential in precision and personalized medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liquid Biopsy for Cancer: Circulating Tumor Cells, Circulating Free DNA or Exosomes? Zhang, W., Xia, W., Lv, Z., et al.[2019]

Citations

1. foundationmedicine.com foundationmedicine.com/test/foundationone-liquid-cdx

FoundationOne Liquid CDx FoundationOne Liquid CDx is an FDA-approved companion diagnostic that analyzes guideline-recommended genes from a simple blood draw.

2. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf19/P190032C.pdf

FoundationOne® Liquid CDx Technical Information 1.2 Efficacy Based on FoundationOne Liquid CDx Results. BRCA1 and BRCA2 alteration status were verified retrospectively by FoundationOne Liquid CDx in 66% (41/ ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7518588/

Clinical and analytical validation of FoundationOne Liquid ... These study results demonstrate that FoundationOne Liquid CDx accurately and reproducibly detects the major types of genomic alterations in ...

4. info.foundationmedicine.com info.foundationmedicine.com/hubfs/FMI%20Labels/FoundationOne_Liquid_CDx_Label_Technical_Info.pdf

FoundationOne® Liquid CDx Technical Information Table ... FoundationOne Liquid CDx is a qualitative next generation sequencing based in vitro diagnostic test that uses targeted high throughput hybridization-based ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05057234?term=FoundationOne&viewType=Table&rank=4

PRecision Oncology Evidence Development in Cancer ... To evaluate the ability of FoundationOne liquid CDx to detect actionable mutations that were not identified on the tissue based NGS oncopanel. 24 months ...

6. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf19/P190032B.pdf

summary of safety and effectiveness data (ssed) The risks of the FoundationOne Liquid CDx for the selection of prostate cancer patients with alterations in BRCA1 or BRCA2 genes, for treatment with rucaparib ...

7. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf19/P190032S001B.pdf

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) On October 26, 2020 the FoundationOne® Liquid CDx test was approved as a companion diagnostic for BRCA1 and BRCA2 alterations in epithelial.

8. foundationmedicine.com foundationmedicine.com/test/foundationone-cdx

FoundationOne CDx | Foundation ... FoundationOne CDx is the first FDA-approved tissue-based broad companion diagnostic (CDx) that is clinically and analytically validated for all solid tumors.