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Erlotinib in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer

Not Applicable
Completed
Conditions
Recurrent Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Interventions
Other: laboratory biomarker analysis
Registration Number
NCT00085280
Lead Sponsor
National Cancer Institute (NCI)
Brief Summary

This clinical trial is studying how well erlotinib works in treating patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

Detailed Description

PRIMARY OBJECTIVES:

I. Prospectively identify downstream markers of EGFR linked signaling pathways that are predictive of response to OSI-774 (Erlotinib) in this population.

SECONDARY OBJECTIVES:

I. Estimate antitumor objective response rate per RECIST. II. Estimate disease control rate (CR+PR+SD). III. Estimate time to progression and overall survival. IV. Estimate if a grade 2 rash is a predictor of response to OSI-774 (Erlotinib) and of patient survival.

V. Assess safety profile of OSI-774 (Erlotinib) in this population. VI. To determine whether smoking status is linked to outcome for advanced NSCLC patients treated with OSI-774 (Erlotinib).

OUTLINE: This is a pilot, multicenter study.

Patients receive oral erlotinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients complete the Smoking Status Survey, a questionnaire regarding smoking habits, at baseline, and then every 3 months during study treatment.

After completion of study treatment, patients are followed every 3 months for 2 years, and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 129 patients will be accrued for this study within 6 months.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
129
Inclusion Criteria
  • Patients must have pathologically confirmed NSCLC

  • Patients must have diagnostic specimen available on paraffin-embedded block

  • Patients must have advanced NSCLC (stage IIIB with a malignant pleural effusion or IV disease, or recurrent disease)

  • Patients must not have received prior chemotherapy or targeted therapy for metastatic disease, including no prior EGFR inhibitor; patient may have received adjuvant chemotherapy for early stage disease (IB-IIIA), or chemo/XRT for stage IIIA or IIIB disease, provided s/he meets all of the following:

    • It has been at least 6 months since completion of patient's adjuvant chemotherapy for early stage disease (IB-IIIA) or chemo/XRT for stage IIIA or IIIB disease
    • Patient now has advanced disease
  • Patients must have measurable disease per RECIST criteria; all sites of disease must be assessed within 4 weeks prior to registration

  • Creatinine < 1.5 mg/dL or a creatinine clearance of > 50 mL/min

  • SGOT(AST) and SGPT(ALT) < 2 x the institution's upper limit of normal

  • Bilirubin < 1.5 mg/dL

  • ANC > 1500/mm^3

  • PLT > 100,000/mm^3

  • Patients must have ECOG performance status 0, 1, or 2

  • Patients with stable, treated brain metastases are eligible (defined as: patients with brain metastases must have been treated and are asymptomatic and are no longer taking corticosteroids)

  • Patients with gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease, are ineligible

  • Pregnant and breast feeding women are excluded from the study because the agent used in this study may be teratogenic to a fetus and there is no information on the excretion of the agents or their metabolites into breast milk

  • Women of childbearing potential and sexually active males must agree to use an accepted and effective method of contraception (hormonal or barrier methods, abstinence) for the duration of the study

  • HIV positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with OSI-774 (Erlotinib)

  • Patients must not have had immuno, hormonal or radiation therapy within 2 weeks prior to entering the study; those who have not recovered from adverse events due to agents administered more than 2 weeks earlier are ineligible; previously irradiated areas can be considered "measurable disease" if there has been documented progression

  • Patients must not have ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements

  • Patients must not have serious non-healing wound, or bone fracture, or major surgical procedure within 21 days prior to study entry

  • Patients taking Warfarin are eligible

  • If the patient is taking Cyp3A4 inducers or inhibitors, they must be discontinued one week prior to starting OSI-774 (Erlotinib)

  • Patients must not be enrolled in any other concurrent clinical trials

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment (erlotinib hydrochloride)erlotinib hydrochloridePatients receive oral erlotinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients complete the Smoking Status Survey, a questionnaire regarding smoking habits, at baseline, and then every 3 months during study treatment.
Treatment (erlotinib hydrochloride)laboratory biomarker analysisPatients receive oral erlotinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients complete the Smoking Status Survey, a questionnaire regarding smoking habits, at baseline, and then every 3 months during study treatment.
Primary Outcome Measures
NameTimeMethod
Response rates and distribution of the mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (Erk)-phosphorylated expression groups based on the Response Evaluation Criteria in Solid Tumors (RECIST)Up to 5 years

A Fisher's exact test with a two-sided 5% type I error rate will be calculated.

Secondary Outcome Measures
NameTimeMethod
Disease control rate (complete response [CR]+partial response [PR]+stable disease [SD])Up to 8 weeks
Time to progressionDate of entry on the study to the appearance of new metastatic lesions or objective tumor progression, up to 5 years
Overall survivalUp to 5 years
Toxicities associated with erlotinib hydrochloride, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0Up to 5 years
Relationship between clinical response and each of the markers using the semiquantitative histo-score methodBaseline

Cox regression models will be used.

Effects of smoking status in terms of disease and survivalUp to 5 years

Descriptive and summary statistics will be conducted on the smoking questionnaire data.

Objective response rate based on the RECISTUp to 5 years

Trial Locations

Locations (1)

Eastern Cooperative Oncology Group

🇺🇸

Boston, Massachusetts, United States

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