We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 2 for:    E4512

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)

This study is currently recruiting participants.
Verified October 2017 by National Cancer Institute (NCI)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02194738
First Posted: July 18, 2014
Last Update Posted: October 31, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
This research 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.

Condition Intervention
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

Study Type: Observational
Official Title: Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.

  • 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.


Other Outcome Measures:
  • 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.

  • 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.

  • 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.


Estimated Enrollment: 8300
Actual Study Start Date: August 18, 2014
Estimated Study Completion Date: September 28, 2021
Estimated Primary Completion Date: September 28, 2021 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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 Sampling
Other: Laboratory Biomarker Analysis
Undergo laboratory analysis via direct sequencing and FISH

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 epidermal growth factor receptor (EGFR) and anaplastic lymphoma receptor tyrosine kinase (ALK) with a central reference standard.

TERTIARY 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.

OUTLINE:

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Criteria

Inclusion Criteria:

  • PATIENT PRE-REGISTRATION ELIGIBILITY CRITERIA:
  • For pre-surgical patients

    • Suspected diagnosis of resectable non-small cell lung cancer; cancers with a histology of ?adenosquamous? are considered a type of adenocarcinoma and thus a ?nonsquamous? histology; patients with squamous cell carcinoma are eligible only if the registering site has EA5142 Institutional Review Board (IRB) approved
    • Suspected clinical stage of IIIA, II (IIA or IIB) or large IB (defined as size >= 4cm); Note: IB tumors < 4cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is >= 4cm
  • For post-surgical patients

    • Completely resected non-small cell lung cancer with negative margins (R0); patients with squamous cell carcinoma are eligible only if the registering site has EA5142 IRB approved
    • Pathologic stage IIIA, II (IIA or IIB) or large IB (defined as size >= 4 cm); Note: IB tumors < 4cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is >= 4cm
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • No patients who have received neoadjuvant therapy (chemo- or radio-therapy) for this lung cancer
  • No locally advanced or metastatic cancer requiring systemic therapy within 5 years prior to registration; no secondary primary lung cancer diagnosed concurrently or within 2 year prior to registration
  • No prior treatment with agents targeting EGFR mutation, ALK rearrangement, and PD-1/PD-L1/CTLA-4
  • No patients known to be pregnant or lactating
  • Patients who have had local genotyping are eligible, regardless of the local result
  • No patients with recurrence of lung cancer after prior resection
  • Note: Post-surgical patients should proceed to registration immediately following preregistration
  • PATIENT REGISTRATION ELIGIBILITY CRITERIA:
  • Completely resected NSCLC with negative margins (R0); cancers with a histology of ?adenosquamous? are considered a type of adenocarcinoma and thus a ?nonsquamous? histology; patients with squamous cell carcinoma are eligible only if the registering site has EA5142 IRB approved
  • Pathologic stage IIIA, IIA or IIB, or large IB (defined as size >= 4cm); Note: IB tumors < 4cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is >= 4cm
  • Tissue available for the required analyses (either clinical tissue block or slides and scrolls)
  • In order to allow for time for central genotyping and eligibility for the ALCHEMIST treatment trial, patients must register within the following eligibility windows, depending on the adjuvant treatment approach:

    • If no adjuvant therapy, register patient within 75 days following surgery
    • If adjuvant chemotherapy or radiotherapy only, register patient within 225 days following surgery
    • If adjuvant chemotherapy and radiation, register patient within 285 days following surgery
  Contacts and Locations
Information from the National Library of Medicine

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


  Show 1283 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Geoffrey Oxnard Alliance for Clinical Trials in Oncology
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02194738     History of Changes
Obsolete Identifiers: NCT02200497
Other Study ID Numbers: 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 )
U10CA180821 ( U.S. NIH Grant/Contract )
U10CA180830 ( U.S. NIH Grant/Contract )
U10CA031946 ( U.S. NIH Grant/Contract )
First Submitted: July 16, 2014
First Posted: July 18, 2014
Last Update Posted: October 31, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms