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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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02193282
First received: July 15, 2014
Last updated: September 26, 2016
Last verified: August 2016
  Purpose
This randomized phase III trial studies how well erlotinib hydrochloride compared to placebo 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.

Condition Intervention Phase
Stage IB Non-Small Cell Lung Carcinoma
Stage IIA Non-Small Cell Lung Carcinoma
Stage IIB Non-Small Cell Lung Carcinoma
Stage IIIA Non-Small Cell Lung Cancer
Drug: Erlotinib Hydrochloride
Other: Laboratory Biomarker Analysis
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized Double Blind Placebo Controlled Study of Erlotinib or Placebo in Patients With Completely Resected Epidermal Growth Factor Receptor (EGFR) Mutant Non-Small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • OS [ Time Frame: The time from randomization until death, assessed up to 10 years ] [ Designated as safety issue: No ]
    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:
  • DFS rate, defined as the proportion of patients alive and disease free at 2 years from the date of randomization [ Time Frame: Time from randomization until documented disease-recurrence or death, whichever occurs first, assessed at 2 years ] [ Designated as safety issue: No ]
    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 10 years ] [ Designated as safety issue: Yes ]
    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.

  • OS rate defined as the proportion of patients alive at 10 years from date of randomization [ Time Frame: At 10 years ] [ Designated as safety issue: No ]
    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.

  • OS rate defined as the proportion of patients alive at 5 years from date of randomization [ Time Frame: At 5 years ] [ Designated as safety issue: No ]
    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 DFS between the erlotinib hydrochloride and placebo arms [ Time Frame: Time from randomization until documented disease-recurrence or death, whichever occurs first, assessed up to 10 years ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 450
Study Start Date: August 2014
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (erlotinib hydrochloride)
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.
Drug: Erlotinib Hydrochloride
Given PO
Other Names:
  • Cp-358,774
  • OSI-774
  • Tarceva
Other: Laboratory Biomarker Analysis
Correlative studies
Placebo Comparator: Arm II (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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Placebo
Given PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess whether adjuvant therapy with erlotinib (erlotinib hydrochloride) will result in improved overall survival (OS) over placebo 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 placebo 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 placebo 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.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: 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 II: 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.

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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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 prior or concurrent malignancies within 5 years, except non-melanoma skin carcinoma and in situ carcinomas
  • 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02193282

  Show 1112 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Ramaswamy Govindan Alliance for Clinical Trials in Oncology
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02193282     History of Changes
Other Study ID Numbers: NCI-2014-01508  NCI-2014-01508  CALGB A081105  A081105  A081105  U10CA180821  U10CA031946 
Study First Received: July 15, 2014
Last Updated: September 26, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 27, 2016