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

1500 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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 data supports the idea that Tissue vs Liquid Biopsy for Cancer Diagnosis is an effective treatment?

The available research shows that liquid biopsy is effective for diagnosing and monitoring various types of cancer, such as lung, colorectal, prostate, melanoma, breast, and pancreatic cancer. Liquid biopsy can detect cancer earlier than traditional methods and provides real-time information about the cancer's behavior. It is noninvasive, meaning it doesn't require surgery to collect samples, and can track how the cancer changes over time, which helps doctors decide on the best treatment. This makes it a promising alternative to traditional tissue biopsies. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment FoundationOne Liquid CDx for cancer diagnosis?

Research shows that liquid biopsies, like FoundationOne Liquid CDx, can effectively detect and monitor cancer by analyzing blood samples for tumor-related markers. This method is noninvasive and can provide real-time information about the cancer, helping doctors make better treatment decisions. ^{1 2 3 4 5}

What safety data exists for FoundationOne Liquid CDx?

The FoundationOne Liquid CDx assay has undergone extensive validation studies, including over 7,500 tests and more than 30,000 unique variants across 300+ genes and 30+ cancer types. The studies demonstrated high accuracy and reproducibility in detecting genomic alterations, with a false positive variant rate of 0.013% and a reproducibility rate of 99.59%. The assay has been approved by the FDA, indicating its safety and efficacy for clinical use. ^{6 7 8 9 10}

Is FoundationOne Liquid CDx safe for humans?

FoundationOne Liquid CDx has been validated in studies involving over 7,500 tests and more than 30,000 unique genetic variants across various cancer types, demonstrating accurate and reproducible results with a very low false positive rate, suggesting it is generally safe for use in humans. ^{6 7 8 9 10}

Is FoundationOne Liquid CDx a promising treatment for cancer diagnosis?

Yes, FoundationOne Liquid CDx is a promising treatment for cancer diagnosis. It uses a simple blood test to find cancer-related materials, making it less invasive than traditional methods. This approach can help doctors detect cancer early, monitor its progress, and choose the best treatment for each patient. ^{1 2 11 12 13}

How is the FoundationOne Liquid CDx treatment different from other cancer diagnosis methods?

FoundationOne Liquid CDx is unique because it uses a liquid biopsy, which involves analyzing a simple blood sample to detect cancer-related genetic material, making it less invasive than traditional tissue biopsies. This method allows for real-time monitoring of cancer and can be particularly useful when tissue samples are hard to obtain. ^{1 2 11 12 13}

Research Team

Cheryl Ho, MD

Principal Investigator

BC Cancer

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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 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]

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]

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]

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 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]

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, 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Perspective and Translational Oncology of Liquid Biopsy. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Liquid Biopsy in Solid Malignancy. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Applications of liquid biopsies for cancer. [2020]

4. Germany pubmed.ncbi.nlm.nih.gov

Liquid Biopsy for Cancer: Circulating Tumor Cells, Circulating Free DNA or Exosomes? [2019]

5. United States pubmed.ncbi.nlm.nih.gov

The Different Facets of Liquid Biopsy: A Kaleidoscopic View. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

[Clinical Utility of Comprehensive Genome Profiling Using FoundationOne CDx in Japanese Population(PROFILE-F Study)]. [2020]

7. United States 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. [2020]

8. Switzerland 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Clinical utility of comprehensive genomic profiling in Japan: Result of PROFILE-F study. [2022]

10. Switzerland 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. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

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

12. Switzerland pubmed.ncbi.nlm.nih.gov

Preliminary Experience of Liquid Biopsy in Lung Cancer Compared to Conventional Assessment: Light and Shadows. [2023]

13. England pubmed.ncbi.nlm.nih.gov

The potential of liquid biopsy in the management of cancer patients. [2022]