Clinical Trials /

Erlotinib Hydrochloride in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Completely Removed by Surgery (An ALCHEMIST Treatment Trial)

NCT02193282

Description:

This phase III ALCHEMIST trial studies how well erlotinib hydrochloride compared to observation works in treating patients with stage IB-IIIA non-small cell lung cancer that has been completely removed by surgery (resected). Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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

Active, not recruiting

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT02193282

Trial Eligibility

Document

Title

  • Brief Title: Erlotinib Hydrochloride in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Completely Removed by Surgery (An ALCHEMIST Treatment Trial)
  • Official Title: Randomized Study of Erlotinib vs Observation in Patients With Completely Resected Epidermal Growth Factor Receptor (EGFR) Mutant Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: NCI-2014-01508
  • SECONDARY ID: NCI-2014-01508
  • SECONDARY ID: s16-02079
  • SECONDARY ID: CALGB A081105
  • SECONDARY ID: A081105
  • SECONDARY ID: A081105
  • SECONDARY ID: U10CA180821
  • SECONDARY ID: U10CA180830
  • SECONDARY ID: U10CA031946
  • NCT ID: NCT02193282

Conditions

  • Lung Non-Squamous Non-Small Cell Carcinoma
  • Stage IB Lung Non-Small Cell Carcinoma AJCC v7
  • Stage II Lung Non-Small Cell Cancer AJCC v7
  • Stage IIA Lung Non-Small Cell Carcinoma AJCC v7
  • Stage IIB Lung Non-Small Cell Carcinoma AJCC v7
  • Stage IIIA Lung Non-Small Cell Cancer AJCC v7

Interventions

DrugSynonymsArms
Erlotinib HydrochlorideCp-358,774, OSI-774, TarcevaArm A (blinded erlotinib hydrochloride)

Purpose

This phase III ALCHEMIST trial studies how well erlotinib hydrochloride compared to observation works in treating patients with stage IB-IIIA non-small cell lung cancer that has been completely removed by surgery (resected). Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To assess whether adjuvant therapy with erlotinib hydrochloride (erlotinib) will result in
      improved overall survival (OS) over observation for patients with completely resected stage
      IB (>= 4 cm)-IIIA epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer
      (NSCLC) (confirmed centrally) following complete resection and standard post-operative
      therapy.

      SECONDARY OBJECTIVES:

      I. To assess whether adjuvant therapy with erlotinib will result in improved disease free
      survival (DFS) over observation for patients with completely resected stage IB (>= 4 cm)-IIIA
      EGFR mutant NSCLC (confirmed centrally) following complete resection and standard
      post-operative therapy, both overall and within the stage subgroups: IB and II/IIIA.

      II. To evaluate the safety profile of erlotinib in the adjuvant setting. III. To assess
      whether adjuvant therapy with erlotinib will result in improved DFS rate at 2 years, and OS
      rate at 5 and 10 years over observation for patients with completely resected stage IB (>= 4
      cm)-IIIA EGFR mutant NSCLC (confirmed centrally) following complete resection and standard
      post-operative therapy, both overall and within the stage subgroups: IB and II/IIIA.

      IV. To assess the primary and secondary objectives in all randomized patients, regardless of
      central confirmation of the EGFR mutant status.

      V. To study detection of circulating EGFR mutations in cell-free plasma deoxyribonucleic acid
      (DNA) as a prognostic marker in resected early stage NSCLC.

      OUTLINE: 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.

      After completion of study treatment, patients are followed up every 6 months for 4 years and
      then yearly for 6 years.

Trial Arms

NameTypeDescriptionInterventions
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)
  • Erlotinib Hydrochloride
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)
    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
    Arm D (observation)Active ComparatorPatients (including patients previously randomized to placebo) undergo observation at least every 6 months for 2 years.

      Eligibility Criteria

              Inclusion Criteria:

          -  Previously registered to A151216, with the result of lung cancer harboring an EGFR
             exon 19 deletion or L858R mutation; the testing must have been performed by one of the
             following criteria:

               1. Patient registered to A151216 and the assessment performed centrally by the
                  protocol-specified laboratory

               2. By a local Clinical Laboratory Improvement Amendments (CLIA) certified
                  laboratory; the report must indicate the result as well as the CLIA number of the
                  laboratory that performed the assay; these patients will also have been
                  registered to A151216, but can be enrolled on A081105 regardless of the central
                  lab results

                    -  Patients with known resistant mutations in the EGFR tyrosine-kinase (TK)
                       domain (T790M) are not eligible

                    -  Patients that are both EGFR mutant and anaplastic lymphoma kinase (ALK)
                       rearrangements will be registered to A081105

          -  Completely resected stage IB (>= 4 cm), II or IIIA non-squamous NSCLC with negative
             margins; patients may not have received neoadjuvant therapy (chemo- or radio-therapy)
             for this lung cancer

          -  Complete recovery from surgery and standard post-operative therapy (if required);
             patients must be completely recovered from surgery at the time of randomization; the
             minimum time requirement between date of surgery and randomization must be at least 28
             days, the maximum time requirement between surgery and randomization must be 90 days
             if no adjuvant chemotherapy was administered, 240 days if adjuvant chemotherapy was
             administered, and 300 days if adjuvant chemotherapy and radiation therapy was
             administered

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  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 years prior to registration

          -  Non-pregnant and non-lactating

          -  No history of cornea abnormalities

          -  Granulocytes >= 1,500/ul

          -  Platelets >= 100,000/ul

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN)

          -  Serum glutamic oxaloacetic transaminase (SGOT) =< 1.5 x ULN

          -  Serum creatinine =< 1.5 x ULN
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Overall survival (OS)
      Time Frame:The time from randomization until death, assessed up to 10 years
      Safety Issue:
      Description:Estimated using the method of Kaplan-Meier survival curves and a 1-sided stratified log rank test (accounting for all the stratification factors) will be used to compare OS between the two arms. Cox proportional hazards model (including time varying coefficients as necessary) will be used to assess whether the distribution of OS times differ with respect to treatment regimen after having adjusted for the stratification factors as well as other potential prognostic and treatment covariates.

      Secondary Outcome Measures

      Measure:Disease free survival (DFS) rate
      Time Frame:Time from randomization until documented disease-recurrence or death, whichever occurs first, assessed at 2 years
      Safety Issue:
      Description:DFS will be defined as the proportion of patients alive and disease free at 2 years from the date of randomization. Estimated using the method of Kaplan-Meier survival curves. A 1-sided stratified log rank test (accounting for all the stratification factors) will be used to compare DFS between the arms, as well as to compare DFS and OS between the arms within the stage groups. Cox proportional hazards model (including time varying coefficients as necessary) will be used to assess potential differences in time to event outcomes after adjusting for the stratification factors and other potential prognostic and treatment covariates.
      Measure:Overall survival (OS) rate at 5 years
      Time Frame:At 5 years
      Safety Issue:
      Description:Will be defined as the proportion of patients alive at 5 years from date of randomization. Estimated using the method of Kaplan-Meier survival curves. A 1-sided stratified log rank test (accounting for all the stratification factors) will be used to compare DFS between the arms, as well as to compare DFS and OS between the arms within the stage groups. Cox proportional hazards model (including time varying coefficients as necessary) will be used to assess potential differences in time to event outcomes after adjusting for the stratification factors and other potential prognostic and treatment covariates.
      Measure:Overall survival (OS) rate at 10 years
      Time Frame:At 10 years
      Safety Issue:
      Description:Will be defined as the proportion of patients alive at 10 years from date of randomization. Estimated using the method of Kaplan-Meier survival curves. A 1-sided stratified log rank test [accounting for all the stratification factors] will be used to compare DFS and OS between the arms within the stage groups. Cox proportional hazards model (including time varying coefficients as necessary) will be used to assess potential differences in time to event outcomes after adjusting for the stratification factors and other potential prognostic and treatment covariates.
      Measure:Overall disease free survival (DFS) between the erlotinib hydrochloride and observation arms
      Time Frame:Time from randomization until documented disease-recurrence or death, whichever occurs first, assessed up to 10 years
      Safety Issue:
      Description:Estimated using the method of Kaplan-Meier survival curves (21). A 1-sided stratified log rank test [accounting for all the stratification factors] will be used to compare DFS between the arms, as well as to compare DFS and OS between the arms within the stage groups. Cox proportional hazards model (including time varying coefficients as necessary) will be used to assess potential differences in time to event outcomes after adjusting for the stratification factors and other potential prognostic and treatment covariates.
      Measure:Incidence of adverse events associated with each treatment arm
      Time Frame:Up to 10 years
      Safety Issue:
      Description:The maximum grade for each type of adverse event will be recorded for each patient and frequency tables will be reviewed to determine the overall patterns. The number and severity of grade 3 + adverse events will be tabulated and summarized. All adverse events analysis will entail comparisons between the arms within Arms A and B, respectively. Analysis of the overall adverse event rates, as well as specific events of interest will involve chi-square tests or Fisher's exact tests.

      Details

      Phase:Phase 3
      Primary Purpose:Interventional
      Overall Status:Active, not recruiting
      Lead Sponsor:National Cancer Institute (NCI)

      Last Updated

      August 27, 2021