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Trial record 1 of 2 for:    E4512
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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 : October 15, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase III 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.

Condition or disease Intervention/treatment Phase
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: Clinical Observation Drug: Crizotinib Other: Cytology Specimen Collection Procedure Drug: Erlotinib Hydrochloride Biological: Nivolumab Other: Placebo Phase 3

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 8300 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Screening
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: A081105 Arm A (blinded erlotinib hydrochloride)
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)
Other: Cytology Specimen Collection Procedure
Undergo collection of blood and tissue
Other Name: Cytologic Sampling

Placebo Comparator: A081105 Arm B (placebo)
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)
Other: Cytology Specimen Collection Procedure
Undergo collection of blood and tissue
Other Name: Cytologic Sampling

Other: Placebo
Given PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy

Experimental: A081105 Arm C (unblinded erlotinib hydrochloride)
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.
Other: Cytology Specimen Collection Procedure
Undergo collection of blood and tissue
Other Name: Cytologic Sampling

Drug: Erlotinib Hydrochloride
Given PO
Other Names:
  • Cp-358,774
  • OSI-774
  • Tarceva

Active Comparator: A081105 Arm D (observation)
Patients (including patients previously randomized to placebo) undergo observation at least every 6 months for 2 years.
Other: Clinical Observation
Undergo observation
Other Name: observation

Other: Cytology Specimen Collection Procedure
Undergo collection of blood and tissue
Other Name: Cytologic Sampling

Experimental: E4512 Arm A (crizotinib)
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.
Drug: Crizotinib
Given PO
Other Names:
  • MET Tyrosine Kinase Inhibitor PF-02341066
  • PF-02341066
  • PF-2341066
  • Xalkori

Other: Cytology Specimen Collection Procedure
Undergo collection of blood and tissue
Other Name: Cytologic Sampling

Active Comparator: E4512 Arm B (observation)
Patients undergo observation.
Other: Clinical Observation
Undergo observation
Other Name: observation

Other: Cytology Specimen Collection Procedure
Undergo collection of blood and tissue
Other Name: Cytologic Sampling

Experimental: EA5142 Arm I (nivolumab)
Patients receive nivolumab IV over 30 minutes on day 1. Courses repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
Other: Cytology Specimen Collection Procedure
Undergo collection of blood and tissue
Other Name: Cytologic Sampling

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Active Comparator: EA5142 Arm II (observation)
Patients are followed serially with imaging for 1 year.
Other: Cytology Specimen Collection Procedure
Undergo collection of blood and tissue
Other Name: Cytologic Sampling




Primary Outcome Measures :
  1. 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.

  2. 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 :
  1. 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.

  2. 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.


Other Outcome Measures:
  1. 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.

  2. 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.

  3. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 >= 4 cm); Note: IB tumors < 4 cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is >= 4 cm; the 7th edition of American Joint Committee on Cancer (AJCC) staging will be utilized
  • 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 < 4 cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is >= 4 cm; the 7th edition of AJCC staging will be utilized
  • 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 >= 4 cm); Note: IB tumors < 4 cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is >= 4 cm; the 7th edition of AJCC staging will be utilized
  • 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

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 1380 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Geoffrey Oxnard Alliance for Clinical Trials in Oncology

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 Posted: July 18, 2014    Key Record Dates
Last Update Posted: October 15, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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
Nivolumab
Erlotinib Hydrochloride
Crizotinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action