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A Study of Erlotinib (Tarceva) in Participants With Non-Small Cell Lung Cancer (NSCLC)

Phase 2
Completed
Conditions
Non-Squamous Non-Small Cell Lung Cancer
Interventions
Registration Number
NCT02774278
Lead Sponsor
Hoffmann-La Roche
Brief Summary

This study will assess potentially predictive markers of efficacy in participants with NSCLC receiving oral erlotinib (Tarceva) therapy. The anticipated time on study treatment is until disease progression, unacceptable toxicity or death.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
264
Inclusion Criteria
  • Advanced NSCLC
  • Tumor accessible for biopsy by bronchoscopy
  • Disease progression following course of standard chemotherapy, or participants unwilling/unable to undergo chemotherapy
Exclusion Criteria
  • Unstable systemic disease
  • Any other malignancies in the last 5 years
  • Brain metastases
  • Previous treatment with therapy acting on the epidermal growth factor receptor (EGFR) axis

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
ErlotinibErlotinibParticipants will receive erlotinib orally daily until disease progression, unacceptable toxicity or death.
Primary Outcome Measures
NameTimeMethod
Number of Differentially Expressed Genes Associated With Clinical BenefitBaseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years

Affymetrix gene expression profiles were primarily analyzed to identify differentially expressed genes between the participants who derived clinical benefit status and those who did not. Analysis was performed using a multivariate linear model (with clinical benefit status, histology, ethnicity, sex, RNA integrity number (RIN), smoking status and stage as predictors), and a False Discovery Rate criteria of below 0.3 as cut-off. Clinical benefit is defined in the Outcome Measure 5.

Number of KRAS Mutation Participants Who Achieved Clinical BenefitBaseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years

Affymetrix gene expression profiles were primarily analyzed to identify differentially expressed genes between the participants who derived clinical benefit status and those who did not. Analysis was performed using a multivariate linear model (with clinical benefit status, histology, ethnicity, sex, RNA integrity number (RIN), smoking status and stage as predictors), and a False Discovery Rate criteria of below 0.3 as cut-off. Number of participants with KRAS gene mutation and who achieved clinical benefit status was reported. Clinical benefit is defined in the Outcome Measure 5.

Number of Epidermal Growth Factor Receptor (EGFR) Mutation Participants Who Achieved Clinical BenefitBaseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years

Affymetrix gene expression profiles were primarily analyzed to identify differentially expressed genes between the participants who derived clinical benefit status and those who did not. Analysis was performed using a multivariate linear model (with clinical benefit status, histology, ethnicity, sex, RNA integrity number (RIN), smoking status and stage as predictors), and a False Discovery Rate criteria of below 0.3 as cut-off. Number of participants with EGFR mutation (L858R/ exon 19 deletion) and who achieved clinical benefit status was reported. Clinical benefit is defined in the Outcome Measure 5.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Clinical Benefit (CR, PR, or Stable Disease [SD] for at Least 12 Weeks After Study Entry) Using RECISTBaseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years

Clinical benefit was defined as either a CR, PR, or SD prior to failure (disease progression, death from any cause, or a second malignancy). CR: complete disappearance on magnetic response imaging of all enhancing tumor and mass effect on a stable or decreasing dose of dexamethasone (or only receiving adrenal replacement doses) accompanied by a stable or improving neurologic examination that was maintained for at least 12 weeks. PR: greater than or equal to 50% reduction in tumor size by bi-dimensional measurement on a stable or decreasing dose of dexamethasone accompanied by a stable or improving neurologic examination that was maintained for at least 12 weeks. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) taking as reference smallest sum of longest dimensions since treatment started associated to non-progressive disease response for non-target lesions. PD: unequivocal progression of existing non-target lesions.

Percentage of Participants With Overall Response of Complete Response (CR) or Partial Response (PR) Using Response Evaluation Criteria in Solid Tumors (RECIST)Baseline until disease progression, unacceptable toxicity or death, evaluated up to 4 years

Tumor response was defined as either a CR or a PR prior to failure (disease progression, death from any cause, or a second malignancy). CR was defined as the complete disappearance on magnetic response imaging of all enhancing tumor and mass effect on a stable or decreasing dose of dexamethasone (or only receiving adrenal replacement doses) accompanied by a stable or improving neurologic examination that was maintained for at least 12 weeks. PR was defined as a greater than or equal to 50 percent (%) reduction in tumor size by bi-dimensional measurement on a stable or decreasing dose of dexamethasone accompanied by a stable or improving neurologic examination that was maintained for at least 12 weeks.

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