Genomic Analysis for Advanced Lung Cancer

Recruiting at 11 trial locations

Overseen By Gerold Bepler, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Barbara Ann Karmanos Cancer Institute

Disqualifiers: Concurrent malignancy, Uncontrolled heart disease, HIV, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

1020 Participants Needed

Trial Summary

What is the purpose of this trial?

This research trial studies comprehensive genomic analysis in tissue samples from patients with non-small cell lung cancer that has come back or is stage IV. Comprehensive genomic analysis may identify specific gene mutations (changes in deoxyribonucleic acid \[DNA\]) and help doctors to tailor treatment to target the specific mutations.

Do I need to stop my current medications for this trial?

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

What data supports the effectiveness of the treatment Comprehensive Genomic Analysis for advanced lung cancer?

Comprehensive Genomic Profiling (CGP) helps identify specific genetic changes in lung cancer, which can guide doctors to choose targeted treatments that are more likely to work for each patient. Studies show that CGP can find treatment options when standard tests do not, and it aligns with guidelines for testing certain genetic markers in lung cancer. ^{1 2 3 4 5}

Is genomic analysis for lung cancer safe for humans?

The research articles focus on the benefits and applications of genomic analysis in lung cancer treatment, but they do not provide specific safety data for humans. ^{2 3 6 7 8}

How is Comprehensive Genomic Analysis different from other treatments for advanced lung cancer?

Comprehensive Genomic Analysis (CGA) is unique because it uses next-generation sequencing (NGS) to identify specific genetic changes in a patient's cancer, allowing for personalized treatment plans. This approach is particularly beneficial when standard molecular tests do not find actionable targets, offering a tailored therapy option based on the individual's unique cancer profile. ^{1 2 7 8 9}

Research Team

Gerold Bepler, M.D., PhD.

Principal Investigator

Barbara Ann Karmanos Cancer Institute

Eligibility Criteria

This trial is for adults with stage IV or recurrent non-small cell lung cancer who have a life expectancy of at least 3 months and are in relatively good health. They must not have had recent serious heart issues, active hepatitis, HIV, or other cancers that could affect the outcome. Pregnant women are excluded.

Inclusion Criteria

Your absolute neutrophil count is higher than 1.5 x 10^9/L.

Laboratory tests should be done within 30 days of enrollment on the trial

I have a recent biopsy (not from a radiated site) that hasn't been followed by systemic therapy.

Exclusion Criteria

I have another cancer, but my doctor thinks it won't affect this treatment.

I am not pregnant or breastfeeding and willing to use birth control if I join the trial.

I do not have serious illnesses like uncontrolled heart issues, recent heart attack, chronic hepatitis, HIV, or active infections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-3 weeks

Genomic Analysis

Patients undergo collection of tissue samples for genomic analysis via mass spectrometry, PCR, and microarray

Up to 21 days

Treatment

Patients may begin therapy based on the results of the genomic analysis

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 3 months for 2 years, every 6 months for 3 years, and then every 12 months thereafter

Treatment Details

Interventions

• Comprehensive Genomic Analysis

Trial Overview The study involves collecting tissue samples from patients to perform comprehensive genomic analysis. This may help identify specific DNA mutations in the cancer cells and allow doctors to customize treatments targeting these mutations.

Participant Groups

Group I: Ancillary-Correlative (comprehensive genomic analysis) Experimental Treatment 2 Interventions

Patients undergo collection of tissue samples for genomic analysis via mass spectrometry, PCR, and microarray. Based on the results of the genomic analysis, patients may begin therapy.

Comprehensive Genomic Analysis is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Comprehensive Genomic Profiling for:

• Identification of specific gene mutations in non-small cell lung cancer

Approved in United States as Comprehensive Genomic Profiling for:

• Identification of specific gene mutations in non-small cell lung cancer

Approved in Canada as Comprehensive Genomic Profiling for:

• Identification of specific gene mutations in non-small cell lung cancer

Approved in Japan as Comprehensive Genomic Profiling for:

• Identification of specific gene mutations in non-small cell lung cancer

Who Is Running the Clinical Trial?

Barbara Ann Karmanos Cancer Institute

Lead Sponsor

Trials

166

Recruited

9,300+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Comprehensive genomic profiling (CGP) of 51 lung adenocarcinoma patients revealed that 58% of those previously negative for EGFR/KRAS/ALK had actionable genomic alterations, indicating potential benefits from targeted therapies.

The study identified a total of 190 genomic alterations, with TP53 mutations being the most common, highlighting the importance of CGP in uncovering additional treatment options for patients with advanced lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomic profiling of lung adenocarcinoma patients reveals therapeutic targets and confers clinical benefit when standard molecular testing is negative. Lim, SM., Kim, EY., Kim, HR., et al.[2022]

Comprehensive genomic profiling (CGP) panels can identify previously undetected driver mutations in thoracic malignancies, leading to new treatment options for 10% of patients, particularly in lung cancer.

CGP results may help predict the effectiveness of immune checkpoint inhibitors (ICIs), as certain mutations were associated with reduced ICI efficacy, highlighting the importance of CGP in guiding treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical application of comprehensive genomic profiling panel to thoracic malignancies: A single-center retrospective study. Kunimasa, K., Sugimoto, N., Kawamura, T., et al.[2023]

Comprehensive genomic profiling (CGP) was successfully performed on 6,832 NSCLC cases, revealing that 71% of patients had at least one genomic alteration in key driver genes, supporting the NCCN guidelines for targeted testing.

CGP not only detects known driver mutations but also identifies additional alterations in 'pan-negative' lung adenocarcinoma cases, potentially guiding patients towards mechanism-driven clinical trials without requiring extra tissue samples.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism-Driven Clinical Trials. Suh, JH., Johnson, A., Albacker, L., et al.[2019]

In a study of 180 patients with untreated advanced solid tumors, comprehensive genomic profiling (CGP) identified actionable genomic alterations in 100% of cases, indicating its high utility in guiding treatment decisions.

The study found that 61% of patients received molecular-based recommended therapy (MBRT) based on CGP results, suggesting that CGP can effectively inform personalized treatment strategies for cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Genomic Profiling in Previously Untreated Advanced Solid Tumors for Identification of Targeted Therapy Opportunities. Matsubara, J., Mukai, K., Kondo, T., et al.[2023]

In a 3-year study involving 96 patients at a community oncology practice, comprehensive genomic profiling (CGP) identified clinically relevant genomic alterations in 86 patients, with 15 receiving targeted therapies based on these results.

CGP detected significant alterations that conventional testing missed in 84% of a subset of patients, leading to treatment changes and facilitating clinical trial enrollment, which may have resulted in an estimated cost savings of $25,000 per patient for the payer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a Collaboration Between a Health Plan, Oncology Practice, and Comprehensive Genomic Profiling Company from the Payer Perspective. Reitsma, M., Fox, J., Borre, PV., et al.[2023]

Next generation sequencing (NGS) of lung squamous cell carcinoma (LUSC) patients revealed that 38% of those tested had potentially targetable genomic alterations, which could qualify them for clinical trials or approved therapies.

The study found that light or never smokers had a higher rate of therapeutic targets (47%) compared to moderate or heavy smokers (35%), suggesting that NGS is particularly beneficial for this group in identifying treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next-generation sequencing informs diagnosis and identifies unexpected therapeutic targets in lung squamous cell carcinomas. Sands, JM., Nguyen, T., Shivdasani, P., et al.[2021]

In a study of 1353 NSCLC patients, a total of 2328 genetic alterations were identified, highlighting the genetic diversity and complexity of this cancer, particularly with co-occurring mutations like TP53 and ALK fusions.

The presence of dual EGFR mutations showed variability in their allele fractions, which may influence treatment responses to targeted therapies, suggesting that genetic profiling could be crucial for personalized treatment strategies in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-occurring genetic alterations and primary EGFR T790M mutations detected by NGS in pre-TKI-treated NSCLCs. Tang, Y., Che, N., Yu, Y., et al.[2020]

A new workflow for next-generation sequencing (NGS) of lung cancer patients significantly reduced the time from biopsy to results, with a median interval of just 10.7 days, and some results available within a week.

This expedited process allowed 93% of patients with actionable genetic alterations to start first-line targeted therapy quickly, with a median treatment initiation time of 19.7 days, highlighting the effectiveness of using frozen tissue for rapid molecular analysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expediting Comprehensive Molecular Analysis to Optimize Initial Treatment of Lung Cancer Patients With Minimal Smoking History. Dagogo-Jack, I., Robinson, H., Mino-Kenudson, M., et al.[2020]

Core needle biopsy (CNB) specimens can provide accurate molecular profiling for advanced lung cancers, showing an 83.9% concordance rate with surgical resection specimens in detecting genetic alterations.

Despite lower DNA yield and allele frequency in CNB specimens, the results for tumor mutational burden and microsatellite instability were comparable to those from resection specimens, indicating that CNB is a reliable method for guiding precision medicine in lung cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accuracy of next-generation sequencing for molecular profiling of small specimen of lung cancer: a prospective pilot study of side-by-side comparison. Ben, X., Tian, D., Zhuang, W., et al.[2022]

References

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

Genomic profiling of lung adenocarcinoma patients reveals therapeutic targets and confers clinical benefit when standard molecular testing is negative. [2022]

2. Singapore pubmed.ncbi.nlm.nih.gov

Clinical application of comprehensive genomic profiling panel to thoracic malignancies: A single-center retrospective study. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism-Driven Clinical Trials. [2019]

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

First-Line Genomic Profiling in Previously Untreated Advanced Solid Tumors for Identification of Targeted Therapy Opportunities. [2023]

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

Effect of a Collaboration Between a Health Plan, Oncology Practice, and Comprehensive Genomic Profiling Company from the Payer Perspective. [2023]

6. Ireland pubmed.ncbi.nlm.nih.gov

Next-generation sequencing informs diagnosis and identifies unexpected therapeutic targets in lung squamous cell carcinomas. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Co-occurring genetic alterations and primary EGFR T790M mutations detected by NGS in pre-TKI-treated NSCLCs. [2020]

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

Expediting Comprehensive Molecular Analysis to Optimize Initial Treatment of Lung Cancer Patients With Minimal Smoking History. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Accuracy of next-generation sequencing for molecular profiling of small specimen of lung cancer: a prospective pilot study of side-by-side comparison. [2022]