Genetic Testing for Early-Stage Lung Cancer

Recruiting at 1848 trial locations

Overseen By Nathaniel R. Evans

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: National Cancer Institute (NCI)

Must not be taking: EGFR inhibitors, ALK inhibitors, PD-1/PD-L1 inhibitors, CTLA-4 inhibitors

Disqualifiers: Neoadjuvant therapy, Metastatic cancer, Pregnancy, others

Compensation: Varies

Number of Visits: 28

Duration: Up to 2 years

8300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This ALCHEMIST trial studies genetic testing in screening patients with stage IB-IIIA non-small cell lung cancer that has been or will be removed by surgery. Studying the genes in a patient's tumor cells may help doctors select the best treatment for patients that have certain genetic changes.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that patients should not have received certain treatments like neoadjuvant therapy or specific targeted therapies before joining the trial.

Is genetic testing for early-stage lung cancer safe for humans?

The research on genetic testing for lung cancer, particularly using liquid biopsies and circulating tumor DNA (ctDNA), shows high technical success and accuracy in detecting genetic changes. These methods are non-invasive and have been used safely in many patients, suggesting they are generally safe for humans. ^{1 2 3 4 5}

How is the Biospecimen Collection treatment for early-stage lung cancer different from other treatments?

The Biospecimen Collection treatment for early-stage lung cancer is unique because it involves collecting genetic material from tumors to analyze DNA and RNA mutations using next-generation sequencing (NGS). This approach provides comprehensive insights into the cancer's genetic makeup, which can guide personalized treatment strategies, unlike traditional methods that may not capture the full genetic diversity of the tumor. ^{2 5 6 7 8}

What data supports the effectiveness of the treatment Biospecimen Collection for early-stage lung cancer?

The research highlights the use of next-generation sequencing (NGS) in lung cancer, which can provide detailed genetic information from small samples, like those collected in biospecimen collection. This approach has been shown to identify important genetic changes in lung cancer, potentially leading to more targeted and effective treatments. ^{6 8 9 10 11}

Who Is on the Research Team?

David E Kozono

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

This trial is for adults who've had surgery to remove non-small cell lung cancer that hasn't spread too far (stage IB-IIIA). They should be in good physical shape and not have had certain other cancers or treatments targeting specific genetic changes. Pregnant or breastfeeding individuals can't join, nor those with a recent second lung cancer.

Inclusion Criteria

I am suspected to have operable lung cancer that is not too advanced.

I must register for the trial within a specific number of days after my surgery, depending on my treatment plan.

I have a specific type of lung cancer that has been fully removed with no cancer left at the edges, and I have not received additional treatment if it's squamous cell carcinoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive genetic testing and are assigned to treatment subprotocols based on genetic mutations

Up to 2 years

Every 21 days for treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Biospecimen Collection

Trial Overview The ALCHEMIST trial is looking at how genetic testing on tumor cells might guide treatment choices after surgery. It includes various interventions like CT scans, drug therapies (Crizotinib, Erlotinib, Nivolumab), chemotherapy agents (Carboplatin, Cisplatin), and observation methods to find the best approach.

How Is the Trial Designed?

Group I: EA5142 Arm I (nivolumab) Experimental Treatment 6 Interventions

Patients receive nivolumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or PET/CT throughout the trial and blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated.

Group II: E4512 Arm A (crizotinib) Experimental Treatment 2 Interventions

Patients receive crizotinib PO BID on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Group III: A081801 Arm C (platinum doublet, combination pembrolizumab) Experimental Treatment 7 Interventions

INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice and pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 13 cycles in the absence of disease progression or unacceptable toxicity.

Group IV: A081801 Arm B (platinum doublet, sequential pembrolizumab) Experimental Treatment 7 Interventions

INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 17 cycles in the absence of disease progression or unacceptable toxicity.

Group V: A081105 Arm C (unblinded erlotinib hydrochloride) Experimental Treatment 2 Interventions

Unblinded patients receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Group VI: A081105 Arm A (blinded erlotinib hydrochloride) Experimental Treatment 1 Intervention

Blinded patients receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. (CLOSED 06/14/17)

Group VII: A081801 Arm A (platinum doublet, observation) Active Control 7 Interventions

INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. CONTINUANCE THERAPY: Patients then undergo observation.

Group VIII: E4512 Arm B (observation) Active Control 2 Interventions

Patients undergo observation.

Group IX: EA5142 Arm II (observation) Active Control 6 Interventions

Patients are followed serially with CT and/or PET/CT imaging for up to 1 year and then during follow-up. Patients also undergo blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated on study.

Group X: A081105 Arm D (observation) Active Control 2 Interventions

Patients (including patients previously randomized to placebo) undergo observation at least every 6 months for 2 years.

Group XI: A081105 Arm B (placebo) Placebo Group 2 Interventions

Patients receive placebo PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. (CLOSED 06/14/17)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A new next-generation sequencing (NGS) technology was developed to analyze low-input, low-quality cancer samples, specifically targeting 135 RNA and 55 DNA markers relevant to non-small cell lung cancer (NSCLC).

This multiomic NGS panel demonstrated high accuracy, achieving 97% agreement with an independent validated NGS panel, allowing for faster and more economical insights into cancer mutations and expression profiles compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Integrated Next-Generation Sequencing System for Analyzing DNA Mutations, Gene Fusions, and RNA Expression in Lung Cancer. Haynes, BC., Blidner, RA., Cardwell, RD., et al.[2023]

The tissue-first approach for testing in treatment-naïve metastatic lung adenocarcinoma patients is the most cost-efficient strategy, incurring an average cost of $2,354 and minimizing monetary loss compared to plasma-first and complementary approaches.

The complementary approach offers the fastest testing turnaround time at 12.7 days, making it a viable option for populations with low EGFR mutation rates, while the plasma-first approach could become preferable if its costs are reduced, especially in populations with higher EGFR mutation rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic Analysis of Tissue-First, Plasma-First, and Complementary NGS Approaches for Treatment-Naïve Metastatic Lung Adenocarcinoma. Yang, SC., Lin, CC., Chen, YL., et al.[2023]

Targeted next generation sequencing (NGS) of liquid biopsies in advanced non-small cell lung cancer (NSCLC) showed a positive percent agreement (PPA) for detecting mutations, with the highest rate of 67.8% for EGFR, indicating that while liquid biopsies can identify some mutations, they may not fully replace tissue biopsies.

Liquid biopsies can be a useful tool for therapeutic decision-making in NSCLC, but they currently do not detect all clinically relevant mutations as effectively as tissue biopsies, highlighting the need for further research to establish their role in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of liquid-based to tissue-based biopsy analysis by targeted next generation sequencing in advanced non-small cell lung cancer: a comprehensive systematic review. Esagian, SM., Grigoriadou, GΙ., Nikas, IP., et al.[2021]

In a study of 24 advanced non-small cell lung cancer (NSCLC) patients, liquid biopsies revealed potential resistance mechanisms in 57% of those progressing on targeted therapies, highlighting the importance of genetic analysis in treatment planning.

The most common resistance mechanisms identified were mutations in ALK and EGFR, found in 38% of patients, indicating that monitoring these genetic changes can inform oncologists about the effectiveness of ongoing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective analysis of liquid biopsies of advanced non-small cell lung cancer patients after progression to targeted therapies using GeneReader NGS platform. Mayo de Las Casas, C., Garzón-Ibañez, M., Jordana-Ariza, N., et al.[2022]

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]

The circulating cell-free tumor DNA sequencing test demonstrated high accuracy and specificity in detecting genetic variants in cancer patients, with positive percent agreement over 99% when compared to traditional tissue-based methods across more than 750 patients.

In a clinical setting involving over 10,000 advanced solid tumor patients, the test showed a high technical success rate of 99.6% and a clinical sensitivity of 85.9%, indicating its feasibility and potential to guide treatment decisions, especially in non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation of a Plasma-Based Comprehensive Cancer Genotyping Assay Utilizing Orthogonal Tissue- and Plasma-Based Methodologies. Odegaard, JI., Vincent, JJ., Mortimer, S., et al.[2022]

Liquid biopsies, which analyze circulating tumor DNA (ctDNA), provide a non-invasive way to gather comprehensive tumor information, making them a promising tool for monitoring lung cancer and identifying genetic alterations.

These blood-based tests can detect genetic changes before they are visible through traditional imaging, allowing for earlier intervention and personalized treatment adjustments based on the tumor's genetic profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liquid biopsies in lung cancer-time to implement research technologies in routine care? Köhn, L., Johansson, M., Grankvist, K., et al.[2020]

In a study of 1,971 patients with advanced non-small-cell lung cancer (NSCLC), 27% had targetable mutations detected through plasma-based ctDNA testing, primarily EGFR-sensitizing mutations.

Patients treated with EGFR-tyrosine kinase inhibitors showed no significant differences in progression-free survival whether their mutations were identified via tissue or plasma testing, indicating that plasma-based profiling is a reliable method for guiding treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes in Non-Small-Cell Lung Cancer Patients Treated With EGFR-Tyrosine Kinase Inhibitors and Other Targeted Therapies Based on Tumor Versus Plasma Genomic Profiling. Tran, HT., Lam, VK., Elamin, YY., et al.[2022]

Next-generation sequencing (NGS) from plasma samples in treatment-naïve patients with non-squamous cell lung carcinoma (NSCC) is feasible and shows good correlation with tissue-based testing, indicating its potential utility in clinical practice.

However, in this study of 24 patients, the impact of liquid biopsy on therapy selection was limited, and it could not replace traditional tissue testing for guiding treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of NGS-based liquid biopsy in untreated late stage non-squamous lung carcinoma in a single institution. Heeke, S., Hofman, V., Ilié, M., et al.[2021]

Circulating tumor DNA (ctDNA) analysis offers a noninvasive method to monitor lung cancers, providing insights into targetable mutations and the tumor's evolution in response to treatment, which traditional tissue biopsies may miss.

The use of ctDNA can help capture intratumoral heterogeneity and real-time changes in drug resistance, suggesting that incorporating ctDNA analysis into clinical trials could enhance precision medicine approaches for lung cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capturing Genomic Evolution of Lung Cancers through Liquid Biopsy for Circulating Tumor DNA. Offin, M., Chabon, JJ., Razavi, P., et al.[2020]

A next-generation sequencing (NGS) assay was developed to detect actionable mutations in cell-free plasma DNA from patients with advanced non-small cell lung cancer (NSCLC), showing 100% sensitivity and specificity for identifying mutations at low allelic frequencies (≥ 0.4%).

The plasma NGS successfully identified a wide range of driver and resistance mutations, including complex alterations, with a sensitivity of 77% for known mutations, indicating its potential for broad implementation in patient care and research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bias-Corrected Targeted Next-Generation Sequencing for Rapid, Multiplexed Detection of Actionable Alterations in Cell-Free DNA from Advanced Lung Cancer Patients. Paweletz, CP., Sacher, AG., Raymond, CK., et al.[2022]

Citations

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

An Integrated Next-Generation Sequencing System for Analyzing DNA Mutations, Gene Fusions, and RNA Expression in Lung Cancer. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Economic Analysis of Tissue-First, Plasma-First, and Complementary NGS Approaches for Treatment-Naïve Metastatic Lung Adenocarcinoma. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Comparison of liquid-based to tissue-based biopsy analysis by targeted next generation sequencing in advanced non-small cell lung cancer: a comprehensive systematic review. [2021]

4. China pubmed.ncbi.nlm.nih.gov

Prospective analysis of liquid biopsies of advanced non-small cell lung cancer patients after progression to targeted therapies using GeneReader NGS platform. [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

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

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

Validation of a Plasma-Based Comprehensive Cancer Genotyping Assay Utilizing Orthogonal Tissue- and Plasma-Based Methodologies. [2022]

7. China pubmed.ncbi.nlm.nih.gov

Liquid biopsies in lung cancer-time to implement research technologies in routine care? [2020]

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

Clinical Outcomes in Non-Small-Cell Lung Cancer Patients Treated With EGFR-Tyrosine Kinase Inhibitors and Other Targeted Therapies Based on Tumor Versus Plasma Genomic Profiling. [2022]

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

Prospective evaluation of NGS-based liquid biopsy in untreated late stage non-squamous lung carcinoma in a single institution. [2021]

10. Egypt pubmed.ncbi.nlm.nih.gov

Capturing Genomic Evolution of Lung Cancers through Liquid Biopsy for Circulating Tumor DNA. [2020]

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

Bias-Corrected Targeted Next-Generation Sequencing for Rapid, Multiplexed Detection of Actionable Alterations in Cell-Free DNA from Advanced Lung Cancer Patients. [2022]