Genetic Testing in Screening Patients With Stage IB-IIIA Non-Small Cell Lung Cancer That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial)
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|ClinicalTrials.gov Identifier: NCT02194738|
Recruitment Status : Recruiting
First Posted : July 18, 2014
Last Update Posted : March 22, 2018
|Condition or disease||Intervention/treatment|
|Large Cell Lung Carcinoma Lung Adenocarcinoma Stage IB Non-Small Cell Lung Carcinoma AJCC v7 Stage IB Squamous Cell Lung Carcinoma AJCC v7 Stage II Non-Small Cell Lung Cancer AJCC v7 Stage II Squamous Cell Lung Carcinoma AJCC v7 Stage IIA Non-Small Cell Lung Carcinoma AJCC v7 Stage IIA Squamous Cell Lung Carcinoma AJCC v7 Stage IIB Non-Small Cell Lung Carcinoma AJCC v7 Stage IIB Squamous Cell Lung Carcinoma AJCC v7 Stage IIIA Non-Small Cell Lung Cancer AJCC v7 Stage IIIA Squamous Cell Lung Carcinoma AJCC v7||Other: Cytology Specimen Collection Procedure Other: Laboratory Biomarker Analysis|
I. To centrally test resected non-small cell lung cancer (NSCLC) for genetic mutations to facilitate accrual to randomized adjuvant studies.
II. To obtain clinically annotated tumor tissue and patient-matched non-malignant deoxyribonucleic acid (DNA) from peripheral blood, as well as detailed epidemiologic and clinical follow-up data, to allow clinically annotated advanced genomic analyses in concert with the National Cancer Institute (NCI) Center for Cancer Genomics (CCG).
I. To characterize the natural history of molecularly characterized NSCLC to allow subsequent development of targeted therapies against genotype-defined subpopulations in the adjuvant and recurrent settings.
II. To cross-validate local genotyping assays for epidermal growth factor receptor (EGFR) and anaplastic lymphoma receptor tyrosine kinase (ALK) with a central reference standard.
I. To study the genomic evolution of lung cancers by comparing genomic characteristics at resection and at recurrence.
II. To understand reasons behind lack of enrollment to adjuvant targeted therapy studies for potentially eligible patients.
III. To study the clinical significance of circulating tumor DNA within the plasma cell-free DNA (cfDNA) from early stage lung cancer patients.
Patients undergo collection of blood and tissue samples for EGFR, ALK, and programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1)/cytotoxic t-lymphocyte-associated protein 4 (CTLA-4) testing via direct sequencing, fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Patients that have had surgery prior to pre-registration will submit samples from the previous surgery for testing.
After completion of study, patients that are not enrolled on either A081105, E4512, or EA5142 are followed up every 6 months for 5 years.
|Study Type :||Observational|
|Estimated Enrollment :||8300 participants|
|Official Title:||Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)|
|Actual Study Start Date :||August 18, 2014|
|Estimated Primary Completion Date :||September 28, 2021|
|Estimated Study Completion Date :||September 28, 2021|
Ancillary-Correlative (marker identification and sequencing)
Patients undergo collection of blood and tissue samples for EGFR and ALK testing via direct sequencing and FISH. Patients that have had surgery prior to pre-registration will submit samples from the previous surgery for testing.
Other: Cytology Specimen Collection Procedure
Undergo collection of blood and tissue
Other Name: Cytologic SamplingOther: Laboratory Biomarker Analysis
Undergo laboratory analysis via direct sequencing and FISH
- Central clinical genotyping to facilitate accrual to the adjuvant Intergroup studies, E4512 and A081105, as measured by rate of accrual [ Time Frame: Up to 4 years ]Central clinical genotyping to facilitate accrual to the adjuvant Intergroup studies, E4512 and A081105, will be measured by the rate of accrual.
- Feasibility of research grade formalin-fixed, paraffin-embedded tissue collection for Center for Cancer Genomics (CCG) analysis, as measured by adequate specimens collected per month [ Time Frame: Up to 4 years ]Research grade formalin-fixed, paraffin-embedded tissue collection for Center for CCG analysis, will be measured by adequate specimens collected per month.
- Disease free survival (DFS) rate for lung cancers which are wild-type for EGFR and ALK [ Time Frame: Time from resection to the earliest of documented disease recurrence confirmed by biopsy, development of a new lung cancer confirmed by biopsy, or death from any cause, assessed at 2 years ]Using genomics performed at CCG, DFS rate will be calculated for each genotype-defined population constituting greater than 1% of the study cohort.
- Agreement of local genotyping methods (direct sequencing of EGFR, ALK fluorescence in situ hybridization [FISH]) with central Clinical Laboratory Improvement Amendments genotyping [ Time Frame: Up to 5 years ]For each locally used assay, agreement will be defined as the proportion of patients deemed mutant (or wild-type) by local and central assessment divided by the number of evaluable patients, where an evaluable patient is one who has a local assessment result and has submitted tissue for central assessment. An agreement rate of 90% or higher between the local assay and the central assessment will be deemed acceptable.
- Spectrum of new mutations identified at recurrence [ Time Frame: Up to 5 years ]Genomic analysis will be performed on tissue collected at time of recurrence and compared to baseline genomics. New mutations in key oncogenes and tumor suppressor genes (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha and phosphatase and tensin homolog, etc) will be quantified.
- Proportions of patients who decline to enroll [ Time Frame: Up to 5 years ]Reasons behind why potentially eligible ALK-rearranged/EGFR mutant patients decline to enroll onto the adjuvant trials will be summarized. Concern with randomization, or not needing further therapy versus those who become otherwise ineligible due to recurrent disease or missing the enrollment window will be catalogued.
- Variability in the levels of baseline cell-free deoxyribonucleic acid (cfDNA) based on the timing of collection of these samples [ Time Frame: Up to 4 years ]The levels of cfDNA (stratified by the timing of collection) will be correlated with clinical outcomes of overall survival and disease-free survival using Kaplan-Meier approach as well as exploratory Cox proportional Hazards models adjusted for baseline smoking, patient, and tumor characteristics as well as treatment information.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02194738
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|Principal Investigator:||Geoffrey Oxnard||Alliance for Clinical Trials in Oncology|