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Trial record 1 of 1 for:    NCT02193282
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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)

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ClinicalTrials.gov Identifier: NCT02193282
Recruitment Status : Recruiting
First Posted : July 17, 2014
Last Update Posted : November 6, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE July 15, 2014
First Posted Date  ICMJE July 17, 2014
Last Update Posted Date November 6, 2019
Actual Study Start Date  ICMJE August 18, 2014
Estimated Primary Completion Date November 4, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 22, 2017)
Overall survival (OS) [ Time Frame: The time from randomization until death, assessed up to 10 years ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 15, 2014)
OS [ Time Frame: The time from randomization until death, assessed up to 5 years ]
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.
Change History Complete list of historical versions of study NCT02193282 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2019)
  • Disease free survival (DFS) rate [ Time Frame: Time from randomization until documented disease-recurrence or death, whichever occurs first, assessed at 2 years ]
    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.
  • Overall survival (OS) rate at 5 years [ Time Frame: At 5 years ]
    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.
  • Overall survival (OS) rate at 10 years [ Time Frame: At 10 years ]
    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.
  • 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 ]
    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.
  • Incidence of adverse events associated with each treatment arm [ Time Frame: Up to 10 years ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2014)
  • DFS rate defined as the proportion of patients alive and disease free at 2 years from the date of randomization [ Time Frame: At 2 years ]
    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.
  • OS rate defined as the proportion of patients alive at 5 years from date of randomization [ Time Frame: At 5 years ]
    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.
  • Incidence of adverse events associated with each treatment arm [ Time Frame: Up to 5 years ]
    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 I and II, 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE Randomized Study of Erlotinib vs Observation in Patients With Completely Resected Epidermal Growth Factor Receptor (EGFR) Mutant Non-Small Cell Lung Cancer (NSCLC)
Brief Summary 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. 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 (erlotinib hydrochloride) 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description:
As of June 15, 2017, sites will sign into RAVE to unblind any patients that had previously enrolled
Primary Purpose: Treatment
Condition  ICMJE
  • EGFR Exon 19 Deletion Mutation
  • EGFR NP_005219.2:p.L858R
  • 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
Intervention  ICMJE
  • Other: Clinical Observation
    Undergo observation
    Other Name: observation
  • Drug: Erlotinib
    Given PO
  • Drug: Erlotinib Hydrochloride
    Given PO
    Other Names:
    • Cp-358,774
    • OSI-774
    • Tarceva
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Placebo
    Given PO
    Other Names:
    • placebo therapy
    • PLCB
    • sham therapy
Study Arms  ICMJE
  • Experimental: 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)
    Interventions:
    • Drug: Erlotinib
    • Drug: Erlotinib Hydrochloride
    • Other: Laboratory Biomarker Analysis
  • Placebo Comparator: 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)
    Interventions:
    • Other: Laboratory Biomarker Analysis
    • Other: Placebo
  • Experimental: 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.
    Interventions:
    • Drug: Erlotinib
    • Drug: Erlotinib Hydrochloride
    • Other: Laboratory Biomarker Analysis
  • Active Comparator: Arm D (observation)
    Patients (including patients previously randomized to placebo) undergo observation at least every 6 months for 2 years.
    Interventions:
    • Other: Clinical Observation
    • Other: Laboratory Biomarker Analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 15, 2014)
450
Original Estimated Enrollment  ICMJE Same as current
Study Completion Date  ICMJE Not Provided
Estimated Primary Completion Date November 4, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02193282
Other Study ID Numbers  ICMJE NCI-2014-01508
NCI-2014-01508 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
s16-02079
CALGB A081105
A081105 ( Other Identifier: Alliance for Clinical Trials in Oncology )
A081105 ( Other Identifier: CTEP )
U10CA180821 ( U.S. NIH Grant/Contract )
U10CA180830 ( U.S. NIH Grant/Contract )
U10CA031946 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ramaswamy Govindan Alliance for Clinical Trials in Oncology
PRS Account National Cancer Institute (NCI)
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP