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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)

NCT02194738

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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: Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)

Clinical Trial IDs

  • ORG STUDY ID: NCI-2014-01509
  • SECONDARY ID: NCI-2014-01509
  • SECONDARY ID: A151216
  • SECONDARY ID: A151216
  • SECONDARY ID: U10CA180821
  • SECONDARY ID: U10CA180830
  • SECONDARY ID: U10CA031946
  • NCT ID: NCT02194738
  • NCT ALIAS: NCT02200497

Conditions

  • 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

Interventions

DrugSynonymsArms
CrizotinibMET Tyrosine Kinase Inhibitor PF-02341066, PF-02341066, PF-2341066, XalkoriE4512 Arm A (crizotinib)
Erlotinib HydrochlorideCp-358,774, OSI-774, TarcevaA081105 Arm C (unblinded erlotinib hydrochloride)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoEA5142 Arm I (nivolumab)

Purpose

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.

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.

      EXPLORATORY 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:

      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 3 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 treatment arms.

      ARM I: Patients receive nivolumab intravenously (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.

      ARM II: Patients are followed serially with imaging for 1 year.

      After completion of study, patients that are not enrolled on either A081105, E4512, or EA5142
      are followed up every 6 months for 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
A081105 Arm A (blinded erlotinib hydrochloride)ExperimentalBlinded 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)
    A081105 Arm B (placebo)Placebo ComparatorPatients 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)
      A081105 Arm C (unblinded erlotinib hydrochloride)ExperimentalUnblinded 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.
      • Erlotinib Hydrochloride
      A081105 Arm D (observation)Active ComparatorPatients (including patients previously randomized to placebo) undergo observation at least every 6 months for 2 years.
        E4512 Arm A (crizotinib)ExperimentalPatients 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.
        • Crizotinib
        E4512 Arm B (observation)Active ComparatorPatients undergo observation.
          EA5142 Arm I (nivolumab)ExperimentalPatients 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.
          • Nivolumab
          EA5142 Arm II (observation)Active ComparatorPatients are followed serially with imaging for 1 year.

            Eligibility 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
                  
            Maximum Eligible Age:N/A
            Minimum Eligible Age:18 Years
            Eligible Gender:All
            Healthy Volunteers:No

            Primary Outcome Measures

            Measure: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
            Safety Issue:
            Description:Central clinical genotyping to facilitate accrual to the adjuvant Intergroup studies, E4512 and A081105, will be measured by the rate of accrual.

            Secondary Outcome Measures

            Measure: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
            Safety Issue:
            Description:Using genomics performed at CCG, DFS rate will be calculated for each genotype-defined population constituting greater than 1% of the study cohort.
            Measure: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
            Safety Issue:
            Description: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.

            Details

            Phase:Phase 3
            Primary Purpose:Interventional
            Overall Status:Recruiting
            Lead Sponsor:National Cancer Institute (NCI)

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