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Phase II Study to Evaluate the Tumor Biochemical Effects of the EGFR Tyrosine Kinase Inhibitor OSI-774 (Erlotinib) Administered Prior to Surgical Resection in Patients With Early Stage Non-Small Cell Lung Cancer

Phase 2
18 Years
Not Enrolling
Stage IA Non-small Cell Lung Cancer, Stage IB Non-small Cell Lung Cancer, Stage IIA Non-small Cell Lung Cancer, Stage IIB Non-small Cell Lung Cancer, Stage IIIA Non-small Cell Lung Cancer

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Trial Information

Phase II Study to Evaluate the Tumor Biochemical Effects of the EGFR Tyrosine Kinase Inhibitor OSI-774 (Erlotinib) Administered Prior to Surgical Resection in Patients With Early Stage Non-Small Cell Lung Cancer


I. To determine the biochemical response rate (> 75% decrease in P-MAPK and/or P-AKT) with
daily oral OSI-774 (erlotinib) for 14 consecutive days in patients with early stage,
operable NSCLC.


I. To evaluate the safety and tolerance of daily oral OSI-774 (erlotinib) as pre-operative
treatment for early stage operable NSCLC.


I. To correlate antiproliferative (Ki-67, p27) and apoptotic (TUNEL assay) tumor responses
to OSI-774 (erlotinib) with pre-therapy tumor and skin EGFR pathway functional status and
post-therapy tumor and skin EGFR pathway inhibition in patients with resectable NSCLC
treated preoperatively with OSI-774 (erlotinib) for 14 days.

II. Assessment of functional EGFR status: HER1, HER-2, HER3, HER4, PHER1, AKT, P-AKT,
MAPK-P-MAPK, STAT-3, P-STAT-3, EGFR-III by immunohistochemistry (IHC).

III. Assessment of proliferative response: Ki67 and p27 by IHC. IV. Assessment of apoptotic
response: TUNEL assay. V. To study the role of the gastrin-releasing factor and estrogen
receptor pathways in the sensitivity and resistance of NSCLC to OSI-774 (erlotinib).

VI. To identify patterns of gene and protein expression pre-therapy and post-therapy that
are associated with tumor clinical, biochemical, antiproliferative, and apoptotic responses.

VII. To study the antitumor activity of OSI-774 (erlotinib) in NSCLC tumors
heterotransplanted in nude mice after surgical resection and to investigate the sequential
molecular changes associated with tumor response to OSI-774 (erlotinib) therapy.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib once daily on days 1-14 or days 1-21 in the absence of
unacceptable toxicity. Patients then undergo surgical resection on the last day of study
drug administration (day 14 or day 21). Patients may receive chemotherapy and/or
radiotherapy after surgical resection at the discretion of the primary physician.

Patients are followed for 5 years after study registration.

Inclusion Criteria:

- Patients with suspicion of lung cancer without distant metastases

- Patients are scheduled to have a tissue diagnostic procedure within 3 to 5 days of

- Patients are willing to allow collection and submission of baseline and post-therapy
tumor tissue, skin and blood samples for this study

- Patients must have ECOG performance status of 0, 1, or 2

- Patients must have no psychological, familial, sociological, or geographic conditions
that will interfere with medical follow-up and compliance with the study protocol

- Patients must have no prior chemotherapy or radiation therapy or no prior anti- EGFR
treatment exposure

- Patients must be able to take oral medication and not have malabsorption syndrome, or
prior gastrointestinal surgery that limits their absorption (i.e. requiring total
parental nutrition)

- Patients must not be using phenytoin, carbamazepine, barbiturates, rifampicin,
phenobarbital, oxcarbazepine, rifapentine, St John's Wort, or any other CYP 3A4
enzyme-inducing agent; any use of these substances must be discontinued at least 2
weeks prior to registration

- Patients must not be taking any anti-coagulants

- Patients must not have been treated with a non-approved or investigational drug
within 21 days prior to pre-registration; patients must not have serious underlying
medical condition that would impair the ability of patient to receive the planned

- Patients with a known hypersensitivity to OSI-774 (erlotinib) are not eligible

- Patients must have histologically confirmed NSCLC; cytologic specimens obtained by
brushing, washing or needle aspiration of defined lesions will be acceptable

- Patients must have stage IA (T1N0M0), stage IB (T2N0M0), stage IIA (T1N1M0), stage
IIB (T2N1M0; T3N0-1M0), or stage IIIA (T1-3N2M0) disease

- Patients with small cell component on histology specimen are not eligible

- A paraffin-embedded cell block and 1-2 segments of frozen tissue demonstrating NSCLC
and obtained during the diagnostic biopsy is available for submission

- Patients must be considered operable candidates and disease must be considered

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

- All females of childbearing potential must have a blood test or urine study
within 1 week, prior to registration to rule out pregnancy

- Women of childbearing potential and sexually active males are strongly advised
to use an accepted and effective method of contraception

- WBC >= 3500/mm^3

- ANC >= 1500/mm^3

- Platelet count >= 100,000/mm^3

- Total bilirubin < 1.5mg/dL

- SGPT and SGOT < 3 times institution's upper limit of normal

- Serum creatinine < 2mg/dl or creatinine clearance >= 20 ml/min

Type of Study:


Study Design:

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

Outcome Measure:

Biochemical response rate in tumor defined as > 75% decrease in P-MAPK and/or P-AKT

Outcome Time Frame:

Up to 5 years

Safety Issue:


Principal Investigator

Steven Keller

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

December 2004

Completion Date:

Related Keywords:

  • Stage IA Non-small Cell Lung Cancer
  • Stage IB Non-small Cell Lung Cancer
  • Stage IIA Non-small Cell Lung Cancer
  • Stage IIB Non-small Cell Lung Cancer
  • Stage IIIA Non-Small Cell Lung Cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Eastern Cooperative Oncology Group Boston, Massachusetts  02215