Genetic Testing for Early-Stage Lung Cancer

Not currently recruiting at 1898 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how genetic testing can tailor treatments for individuals with early-stage lung cancer, specifically stage IB-IIIA non-small cell lung cancer, that has been or will be surgically removed. Researchers will study participants' tumor cells for genetic changes to determine the most effective treatment option. The trial includes multiple treatment paths, such as various drug therapies and observation, based on genetic findings. It suits those with non-small cell lung cancer that has been surgically removed or is planned for surgery and who have not received prior treatments like chemotherapy or radiation. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could personalize future cancer treatments.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that erlotinib hydrochloride worked well and was generally tolerated by patients with advanced non-small cell lung cancer, particularly among Asian populations. Some patients experienced side effects such as skin rash and a lung condition that can cause scarring.

Pembrolizumab has been shown to be safe for early-stage non-small cell lung cancer. It is already approved for treating several types of cancer, suggesting general safety, though side effects like tiredness and nausea can occur.

Research on nivolumab indicates it is generally safe for non-small cell lung cancer. Common side effects include tiredness and nausea, but serious reactions like lung inflammation and breathing problems have been reported in some cases.

Crizotinib, used in patients with specific genetic markers, has also shown safety and effectiveness. It outperformed chemotherapy in some studies, but side effects like vision problems and nausea may occur.

Overall, these treatments are mostly well-tolerated but can have some side effects. Always consult a doctor for personalized advice. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores genetic testing for early-stage lung cancer, which could revolutionize how we approach this disease. Unlike traditional methods that often follow a one-size-fits-all treatment, this trial aims to personalize therapy based on an individual's genetic makeup. This approach could lead to more effective treatments with fewer side effects, targeting the cancer more precisely. If successful, this could mean faster and more accurate treatments, tailoring therapy to the patient rather than the general condition.

What evidence suggests that this trial's treatments could be effective for early-stage lung cancer?

Research has shown that erlotinib hydrochloride, which participants in this trial may receive, yields promising results for treating non-small cell lung cancer (NSCLC). Studies indicate it can extend life and ease symptoms like trouble breathing, pain, and coughing, especially in patients who have undergone previous treatments. Pembrolizumab, another treatment option in this trial, has also helped some patients live longer compared to traditional chemotherapy. Nivolumab, also tested in this trial, can shrink tumors early in treatment for some patients and provide lasting benefits. Crizotinib, another treatment under study, proves effective in advanced NSCLC, helping patients go longer without their cancer worsening compared to chemotherapy. Overall, these treatments offer hope for better outcomes in lung cancer patients. ^{2 3 5 6 7}

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

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4093347/

Crizotinib: A Breakthrough for Targeted Therapies in Lung ... Initial response rates to crizotinib therapy were reported to be between 50% and 61% (Camidge et al., 2011; Crino et al., 2011). Although many patients ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0169500224003507

Efficacy and safety of crizotinib in the treatment ... Meta-analysis of 14 crizotinib aNSCLC RWE studies yielded a pooled ORR of 70.6 %, median rwPFS of 14.5 mo, and OS of 40.2 mo. •. The real-world safety and ...

3. medscape.com medscape.com/viewarticle/crizotinib-not-beneficial-resected-early-alk-nsclc-2025a1000nxr

Crizotinib Not Beneficial in Resected Early ALK+NSCLC At median follow-up of 58.3 months, median disease-free survival (DFS) was 72.8 months vs 75.1 months in 75 and 79 patients who were ALK+ on ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1408440

First-Line Crizotinib versus Chemotherapy in ALK-Positive ... Results. Progression-free survival was significantly longer with crizotinib than with chemotherapy (median, 10.9 months vs. 7.0 months; hazard ...

5. cancer.gov cancer.gov/types/lung/research/crizotinib

Crizotinib for Advanced Non-Small Cell Lung Cancer - NCI Results from an open-label phase III trial of 343 patients show that crizotinib is effective as first-line therapy for patients with advanced ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3936578/

Activity and safety of crizotinib in patients with ALK-positive ... Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study

7. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizer_reports_positive_phase_3_study_outcome_of_xalkori_crizotinib_compared_to_chemotherapy_in_previously_untreated_patients_with_alk_positive_advanced_non_small_cell_lung_cancer_nsclc

Pfizer Reports Positive Phase 3 Study Outcome Of ... Crizotinib is the Only Agent That Demonstrated Superior PFS Over Chemotherapy in Two Global Randomized Studies in First- and Second-Line ...