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 : May 17, 2024
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Tracking Information | |||||
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First Submitted Date ICMJE | July 16, 2014 | ||||
First Posted Date ICMJE | July 18, 2014 | ||||
Last Update Posted Date | May 17, 2024 | ||||
Actual Study Start Date ICMJE | September 26, 2014 | ||||
Estimated Primary Completion Date | September 28, 2026 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
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Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures |
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Original Other Pre-specified Outcome Measures |
Spectrum of new mutations identified at recurrence [ Time Frame: Up to 5 years ] 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.
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Descriptive Information | |||||
Brief Title ICMJE | 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) | ||||
Official Title ICMJE | Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) | ||||
Brief Summary | 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. | ||||
Detailed Description | PRIMARY OBJECTIVES: 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). SECONDARY OBJECTIVES: 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 EGFR and ALK and PD-L1 immunohistochemistry (IHC) with a central reference standard, when available. EXPLORATORY/OTHER OBJECTIVES: 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. IV. To perform proteomic analyses on lung cancer specimens obtained at the time of resection (to identify prognostic biomarkers). OUTLINE: STEP 1 (SCREENING): 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. STEP 2 (TREATMENT): Patients with a mutation targeted by one or more of the investigational drugs used in this study or those without mutations are assigned to 1 of 4 treatment subprotocols. A081105: Patients are randomized to 1 of 4 treatment arms. ARM A (BLINDED ERLOTINIB- CLOSED 06/14/17): Blinded patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM B (PLACEBO- CLOSED 06/14/17): 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. ARM C (UNBLINDED ERLOTINIB): 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. ARM D (OBSERVATION): Patients (including patients previously randomized to placebo) undergo observation at least every 6 months for 2 years. E4512: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive crizotinib PO twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM B: Patients undergo observation. EA5142: Patients are randomized to 1 of 2 arms. ARM I: Patients receive nivolumab intravenously (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 computed tomography (CT) and/or positron emission tomography (PET)/CT throughout the trial and blood sample collection during screening and follow-up. Patients may undergo an echocardiography (ECHO) as clinically indicated on study. ARM II: 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. A081801: Patients are randomized to 1 of 3 arms. ARM A: 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. ARM B: 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 intravenously (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. ARM C: 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. *ACCEPTABLE REGIMENS: DOUBLET I: Patients receive cisplatin IV over 1-2 hours and pemetrexed IV over 10 minutes on day 1 of each cycle. DOUBLET II: Patients receive carboplatin IV over 30 minutes and pemetrexed IV over 10 minutes on day 1 of each cycle. DOUBLET III: Patients receive cisplatin IV over 1-2 hours on day 1 of each cycle and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 of each cycle. DOUBLET IV: Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1 of each cycle. After completion of study, patients that are not enrolled on either A081105, E4512, EA5142, or A081801 are followed up every 6 months for 5 years. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Not Applicable | ||||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Screening |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Kehl KL, Zahrieh D, Yang P, Hillman SL, Tan AD, Sands JM, Oxnard GR, Gillaspie EA, Wigle D, Malik S, Stinchcombe TE, Ramalingam SS, Kelly K, Govindan R, Mandrekar SJ, Osarogiagbon RU, Kozono D. Rates of Guideline-Concordant Surgery and Adjuvant Chemotherapy Among Patients With Early-Stage Lung Cancer in the US ALCHEMIST Study (Alliance A151216). JAMA Oncol. 2022 May 1;8(5):717-728. doi: 10.1001/jamaoncol.2022.0039. | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
8300 | ||||
Original Estimated Enrollment ICMJE |
8000 | ||||
Estimated Study Completion Date ICMJE | September 28, 2026 | ||||
Estimated Primary Completion Date | September 28, 2026 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE | |||||
Listed Location Countries ICMJE | Guam, Puerto Rico, United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT02194738 | ||||
Other Study ID Numbers ICMJE | NCI-2014-01509 NCI-2014-01509 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) A151216 ( Other Identifier: Alliance for Clinical Trials in Oncology ) A151216 ( Other Identifier: CTEP ) U10CA031946 ( U.S. NIH Grant/Contract ) U10CA180821 ( U.S. NIH Grant/Contract ) U10CA180830 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Current Responsible Party | National Cancer Institute (NCI) | ||||
Original Responsible Party | Same as current | ||||
Current Study Sponsor ICMJE | National Cancer Institute (NCI) | ||||
Original Study Sponsor ICMJE | Same as current | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE |
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PRS Account | National Cancer Institute (NCI) | ||||
Verification Date | April 2024 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |