Genome Sequencing for Personalized Cancer Therapy

Overseen By Janessa Laskin, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: British Columbia Cancer Agency

Disqualifiers: Significant medical condition, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

5000 Participants Needed

Trial Summary

What is the purpose of this trial?

The genomic heterogeneity of cancers implies that to effectively use targeted therapies the investigators will need to assess each individual cancer and match it to a biologically relevant targeted therapy. The investigators will use full genome sequencing to try to identify cancer "drivers" and corresponding drugs that may inhibit these pathways.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Genome Sequencing for Personalized Cancer Therapy?

Research shows that next-generation sequencing (NGS) can identify specific genetic changes in cancer, which helps doctors choose treatments that are more likely to work for individual patients. However, the effectiveness can vary, as some patients benefit from treatments based on NGS results, while others do not. ^{1 2 3 4 5}

Is genome sequencing safe for humans?

The research articles do not provide specific safety data for genome sequencing, but they discuss its widespread use in cancer research and treatment, suggesting it is generally considered safe for these applications. ^{2 3 4 6 7}

How is genome sequencing used in personalized cancer therapy different from other treatments?

Genome sequencing (also known as next-generation sequencing or NGS) is unique because it analyzes the entire genetic makeup of a cancer, identifying specific mutations that can guide personalized treatment plans. This approach allows for tailored therapies based on the genetic profile of the tumor, potentially improving treatment effectiveness compared to standard treatments that do not consider individual genetic differences. ^{3 4 6 8 9}

Research Team

Janessa Laskin, MD

Principal Investigator

British Columbia Cancer Agency

Eligibility Criteria

This trial is for adults with cancer who can provide tissue samples, have a life expectancy of at least 6 months, and are fit enough to potentially participate in future clinical trials. They must be willing to share their genomic data and understand it may guide treatment options.

Inclusion Criteria

I am open to being contacted for future studies and believe I would be fit for clinical trials.

My organs are working well.

I agree to let my stored tissue samples be used for research, even if they are all used up.

Exclusion Criteria

I do not want to know about specific genetic findings from my tests.

Significant medical condition that in the opinion of the treating or consenting oncologist and/or the POG central office review team renders the subject not suitable for participation. This includes the likelihood that a subject would be suitable for a clinical trial within 12 weeks after POG biopsy

Unwilling or unable to provide treatment and outcome follow-up information to the BC Cancer or affiliated investigators

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Genome Sequencing

Comprehensive DNA and RNA sequencing is performed followed by an in-depth bioinformatic analysis to identify somatic mutations, gene expression changes or other abnormalities

Ongoing

Weekly meetings for genomic report discussions

Treatment Decision

Clinicians discuss genomic reports and come to a consensus on appropriate systemic therapies based on results

Ongoing

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Genome sequencing

Trial Overview The trial uses full genome sequencing on individual cancers to identify 'drivers' of the disease and match them with targeted therapies that could inhibit these pathways. It aims to personalize cancer treatment based on genetic analysis.

Participant Groups

Group I: Genome Sequencing Experimental Treatment 1 Intervention

There is only one arm to this study.

Genome sequencing is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Genomic sequencing for:

• Diagnostic tool for various cancers
• Personalized medicine

Approved in United States as Genomic sequencing for:

• Diagnostic tool for various cancers
• Personalized medicine
• Genetic testing

Approved in Canada as Genomic sequencing for:

• Diagnostic tool for various cancers
• Personalized medicine

Approved in Japan as Genomic sequencing for:

• Diagnostic tool for various cancers
• Personalized medicine

Approved in China as Genomic sequencing for:

• Diagnostic tool for various cancers
• Personalized medicine

Approved in Switzerland as Genomic sequencing for:

• Diagnostic tool for various cancers
• Personalized medicine

Who Is Running the Clinical Trial?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

BC Cancer Foundation

Collaborator

Trials

20

Recruited

8,600+

Findings from Research

Next-generation sequencing (NGS) can identify potential treatment targets in patients with advanced solid tumors, with 10 out of 30 patients receiving therapies based on genomic profiling, although only 3 patients showed significant benefit from this approach.

The study found that while the median progression-free survival (PFS) for patients treated with targeted therapies based on NGS was 12 weeks, this was not significantly better than the 48 weeks PFS observed in the control group, highlighting the need for further research and clinical guidelines to optimize NGS use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next-generation sequencing in patients with advanced cancer: are we ready for widespread clinical use? A single institute's experience. Grenader, T., Tauber, R., Shavit, L.[2018]

The quality improvement project successfully reduced the median time from pathologic diagnosis to next-generation sequencing (NGS) results for metastatic non-small-cell lung cancer (NSCLC) from 24 days to 16 days, enhancing the speed of treatment decisions.

By streamlining communication and workflows between departments, the total time from diagnosis to appropriate treatment was decreased from 33 days to 22 days, demonstrating the effectiveness of a systems-focused approach in a community healthcare setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving Time to Molecular Testing Results in Patients With Newly Diagnosed, Metastatic Non-Small-Cell Lung Cancer. Ossowski, S., Neeman, E., Borden, C., et al.[2023]

Performing plasma cell-free DNA (cfDNA) next-generation sequencing (NGS) before the pathologic diagnosis in hospitalized patients with suspected metastatic non-small-cell lung cancer (NSCLC) significantly reduces the time to obtain genotyping results, with a median of just 3 days compared to 18 days for standard plasma NGS and 35.5 days for tumor NGS.

This early genotyping approach identified actionable genomic variants in 45% of patients, allowing 20% to receive targeted therapies sooner, highlighting its potential to improve treatment initiation for patients with rapidly progressing disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma cfDNA Genotyping in Hospitalized Patients With Suspected Metastatic NSCLC. Cheng, ML., Milan, MSD., Tamen, RM., et al.[2022]

In a study of 932 non-small-cell lung cancer (NSCLC) cases, actionable mutations were found in 65% of patients, highlighting the effectiveness of next-generation sequencing for identifying targeted therapeutic options.

The study identified JAK2 p.V617F mutations in 1% of cases and JAK3 germline mutations in 6.7%, suggesting these mutations could indicate sensitivity to JAK inhibitors and anti-PD1 immunotherapy, warranting further research into their clinical implications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer gene profiling in non-small cell lung cancers reveals activating mutations in JAK2 and JAK3 with therapeutic implications. Li, SD., Ma, M., Li, H., et al.[2022]

In a study of 305 patients who underwent next-generation sequencing (NGS) for tumor samples, only 11.1% of usable reports led to a change in management, indicating limited clinical utility of NGS in this setting.

While 40.21% of reports identified targetable mutations for on-label therapies and 66.67% for off-label therapies, the actual implementation of off-label treatments resulted in poor patient responses, highlighting the need for cautious interpretation of NGS results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next-Generation Sequencing in 305 Consecutive Patients: Clinical Outcomes and Management Changes. Davis, W., Makar, G., Mehta, P., et al.[2020]

The completion of the Human Genome Project in 2003 has significantly advanced cancer research, leading to the development of personalized medicine that tailors treatments based on individual genetic profiles.

Next-generation sequencing (NGS) has made it easier and more cost-effective to analyze tumor DNA, allowing for the identification of genetic alterations that can predict how well a patient will respond to specific cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complexity of genome sequencing and reporting: Next generation sequencing (NGS) technologies and implementation of precision medicine in real life. Morganti, S., Tarantino, P., Ferraro, E., et al.[2019]

Next-Generation Sequencing (NGS) allows for comprehensive gene mutation profiling in tumors, which can aid in various oncology applications such as screening for cancer predisposition, classifying tumors, selecting treatments, and monitoring treatment responses.

Ongoing clinical studies are exploring the effectiveness of genotype-informed treatment selection, with the potential for focused gene panels to become the preferred method in molecular diagnostics due to their analytical advantages and decreasing costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical utility of molecular genetic cancer profiling. Joseph, L.[2018]

Next generation sequencing (NGS) has revolutionized the field of genomics by allowing for the rapid and simultaneous sequencing of large amounts of fragmented DNA, which is crucial for understanding cancer genetics.

This advanced technology enhances our ability to identify genetic mutations and variations in tumors, leading to better insights into cancer mechanisms and potential targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Next Generation Sequencing in Cancer Research. Nones, K., Patch, AM.[2020]

The study developed a targeted next-generation sequencing (NGS) assay that can accurately detect genetic mutations in cancer with an impressive analytic accuracy of 98%, using as little as 3 ng of DNA from formalin-fixed samples.

This NGS platform demonstrates high sensitivity (97%) and perfect specificity (100%), making it a valuable tool for analyzing challenging specimens with low DNA yield in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of a microfluidics-based next generation sequencing assay for clinical oncology diagnostics. Henzler, C., Schomaker, M., Yang, R., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Next-generation sequencing in patients with advanced cancer: are we ready for widespread clinical use? A single institute's experience. [2018]

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

Improving Time to Molecular Testing Results in Patients With Newly Diagnosed, Metastatic Non-Small-Cell Lung Cancer. [2023]

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

Plasma cfDNA Genotyping in Hospitalized Patients With Suspected Metastatic NSCLC. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Cancer gene profiling in non-small cell lung cancers reveals activating mutations in JAK2 and JAK3 with therapeutic implications. [2022]

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

Next-Generation Sequencing in 305 Consecutive Patients: Clinical Outcomes and Management Changes. [2020]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Complexity of genome sequencing and reporting: Next generation sequencing (NGS) technologies and implementation of precision medicine in real life. [2019]

7. England pubmed.ncbi.nlm.nih.gov

The clinical utility of molecular genetic cancer profiling. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

The Impact of Next Generation Sequencing in Cancer Research. [2020]

9. China pubmed.ncbi.nlm.nih.gov

Optimization of a microfluidics-based next generation sequencing assay for clinical oncology diagnostics. [2022]