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A Pilot Study to Determine if Downstream Markers of EGFR Linked Signaling Pathways Predict Response to OSI-774 (Erlotinib) in the First-Line Treatment of Patients With Advanced Non-Small Cell Lung Cancer

18 Years
Not Enrolling
Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

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Trial Information

A Pilot Study to Determine if Downstream Markers of EGFR Linked Signaling Pathways Predict Response to OSI-774 (Erlotinib) in the First-Line Treatment of Patients With Advanced Non-Small Cell Lung Cancer


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


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

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.

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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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)

Outcome Description:

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

Outcome Time Frame:

Up to 5 years

Safety Issue:


Principal Investigator

Julie Brahmer

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

September 2004

Completion Date:

Related Keywords:

  • Recurrent Non-Small Cell Lung Cancer
  • Stage IIIB Non-Small Cell Lung Cancer
  • Stage IV Non-Small Cell Lung Cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Eastern Cooperative Oncology Group Boston, Massachusetts  02215