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Erlotinib in Treating Patients With Stage I-IIIA Non-Small Cell Lung Cancer Undergoing Surgical Resection

Primary Purpose

Stage IA Non-small Cell Lung Cancer, Stage IB Non-small Cell Lung Cancer, Stage IIA Non-small Cell Lung Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
erlotinib hydrochloride
therapeutic endoscopic surgery
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage IA Non-small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Eastern Cooperative Oncology Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (erlotinib)

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Tolerability of erlotinib, graded according to the NCI CTCAE version 3.0

Full Information

First Posted
July 8, 2004
Last Updated
June 4, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00087269
Brief Title
Erlotinib in Treating Patients With Stage I-IIIA Non-Small Cell Lung Cancer Undergoing Surgical Resection
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Terminated
Study Start Date
December 2004 (undefined)
Primary Completion Date
April 2006 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This phase II trial is studying how well erlotinib works in treating patients with stage I, stage II, or stage IIIA non-small cell lung cancer. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Giving erlotinib before surgery may shrink the tumor so that it can be removed.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
110 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (erlotinib)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
erlotinib hydrochloride
Other Intervention Name(s)
CP-358,774, erlotinib, OSI-774
Intervention Description
Given orally
Intervention Type
Procedure
Intervention Name(s)
therapeutic endoscopic surgery
Intervention Description
Undergo surgical resection
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Biochemical response rate in tumor defined as > 75% decrease in P-MAPK and/or P-AKT
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Tolerability of erlotinib, graded according to the NCI CTCAE version 3.0
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Keller
Organizational Affiliation
Eastern Cooperative Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
Eastern Cooperative Oncology Group
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States

12. IPD Sharing Statement

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Erlotinib in Treating Patients With Stage I-IIIA Non-Small Cell Lung Cancer Undergoing Surgical Resection

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