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
18 Years
N/A
Both
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
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
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
I. To evaluate the safety and tolerance of daily oral OSI-774 (erlotinib) as pre-operative
treatment for early stage operable NSCLC.
TERTIARY OBJECTIVES:
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
pre-registration
- 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
treatment
- 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
resectable
- 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:
Interventional
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:
No
Principal Investigator
Steven Keller
Investigator Role:
Principal Investigator
Investigator Affiliation:
Eastern Cooperative Oncology Group
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-02950
NCT ID:
NCT00087269
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
Name | Location |
|---|---|
| Eastern Cooperative Oncology Group | Boston, Massachusetts 02215 |
