Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Gefitinib in Treating Patients Who Are Undergoing Surgery for Stage I, Stage II, or Stage III Non-Small Cell Lung Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Active	18 and over	NCI, Pharmaceutical / Industry	MCC-13922 ZENECA-IRUSIRES0256, MCC-IRB-102794, NCT00104728

Objectives

Primary

1. Determine the effects of neoadjuvant gefitinib on downstream signaling pathways, including Src-Stat3, PI3K/Akt, ERK activity, and Bcl-2 family members in patients with resectable stage I-IIIA non-small cell lung cancer.
2. Determine the effects of this drug on cell cycle and apoptosis within the primary tumor, by measuring changes in pre- and post-treatment Ki-67, Mcm2, cleaved caspase-3, and ApoTag, in these patients.

Secondary

1. Determine the clinical response rate in patients treated with this drug.
2. Determine the pathological response rate, defined as > 95% necrosis or fibrosis in the pathological specimen, in patients treated with this drug.
3. Determine the metabolic activity of this drug in these patients.
4. Determine the safety, tolerability, and feasibility of this drug, in terms of toxicity and post-treatment resectability, in these patients.
5. Correlate plasma and tumor concentrations of this drug with changes in post-treatment molecular markers in these patients.
6. Identify a gene profile that predicts response to this drug in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed resectable non-small cell lung cancer (NSCLC), meeting 1 of the following clinical staging criteria:
  • Stage IA or IB (T1-2, N0)
  • Stage II (T1-2, N1 with negative mediastinoscopy or T3, N0)
  • Stage IIIA (T3, N1 with negative mediastinoscopy)
    • Level 10 hilar nodes may be positive provided mediastinoscopy is negative



• The following are not allowed (as evidenced by clinical staging criteria [CT scan, positron-emission tomography (PET) scan, or mediastinoscopy):
  • Positive N2 lymph nodes (ipsilateral/subcarinal mediastinal lymph nodes)
  • Positive N3 lymph nodes (contralateral mediastinal/hilar and supraclavicular/scalene lymph nodes)
  • T4 primary tumor (malignant pleural effusion or mediastinal invasion)
  • Symptomatic tumors (T3, N0-1) involving the superior sulcus (i.e., Pancoast tumors)



• Measurable disease by contrast-enhanced CT scan



• No metastatic disease (except peribronchial or hilar lymph node involvement [N1]) by fludeoxyglucose F 18 PET scan



• No malignant pleural effusion by preoperative evaluation
  • Pleural effusions visible only on CT scan that are not large enough for safe thoracentesis are allowed
  • No exudative effusions (even if cytologically negative), as evidenced by any of the following:
    • Ratio of pleural fluid protein to serum protein > 0.5
    • Ratio of pleural fluid lactic dehydrogenase (LDH) to serum LDH ≥ 0.6
    • Pleural fluid LDH > 200 IU/L



• No superior vena cava syndrome



• No spinal cord compression

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• No prior or concurrent systemic chemotherapy for NSCLC

Endocrine therapy

• Not specified

Radiotherapy

• No prior or concurrent radiotherapy for NSCLC

Surgery

• Recovered from prior oncologic or other major surgery
• At least 5 years since prior resection of lung disease
• No prior surgery for NSCLC
• No concurrent ophthalmic surgery

Other

• More than 30 days since prior non-approved or investigational drugs
• No other concurrent therapy for NSCLC
• No other concurrent investigational therapy
• No concurrent use of any of the following medications:
  • Phenytoin
  • Carbamazepine
  • Barbiturates (e.g., phenobarbital)
  • Rifampin
  • Hypericum perforatum (St. John's wort)

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 4,000/mm³
• Absolute granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST or ALT ≤ 2 times ULN
• Alkaline phosphatase ≤ 2 times ULN

Renal

• Creatinine < 1.5 times ULN

Cardiovascular

• No uncontrolled ventricular arrhythmia
• No myocardial infarction within the past 3 months

Pulmonary

• Pre-resection FEV₁ > 2.0 L

  OR

• Predicted post-resection FEV₁ > 1.0 L
• No clinically active interstitial lung disease
  • Chronic stable asymptomatic radiographic changes allowed
• No post-obstructive pneumonia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Willing to provide tumor biopsy pre- and post-gefitinib administration AND undergo PET scan
• No known severe hypersensitivity to study drug or any of its excipients
• No uncontrolled major seizure disorder
• No unstable or uncontrolled diabetes mellitus
• No serious infection requiring IV antibiotics
• No grade 3 neuropathy
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No other unstable or serious medical condition that would preclude study treatment or surgery
• No psychiatric disorder that would preclude giving informed consent
• No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow up
• No other significant clinical disorder or laboratory finding that would preclude study participation

Expected Enrollment

A total of 50 patients will be accrued for this study within 12.5 months.

Outcomes

Effect of neoadjuvant gefitinib on downstream signaling pathways
Effect of this drug on cell cycle and apoptosis

Clinical response rate
Metabolic activity
Pathological response rate
Safety
Tolerability
Feasability
Correlation of plasma and tumor concentrations with changes in post-treatment molecular markers
Gene profile

Outline

This is an open-label, pilot study.

Patients receive oral gefitinib once daily for 4 weeks in the absence of disease progression or unacceptable toxicity.

Within 3 days after completion of gefitinib, patients undergo restaging evaluation. Patients whose disease is still considered resectable proceed to surgery. Patients undergo thoracotomy with lobectomy or pneumonectomy OR sleeve resection. Patients also undergo mediastinal lymph node dissection. After surgical resection, treatment with gefitinib may continue off study at the discretion of the principal investigator.

After completion of study therapy, patients are followed at 30 days, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Eric Haura, MD, Protocol chair		Ph: 813-903-6826; 888-663-3488 Email: hauraeb@moffitt.usf.edu

U.S.A.
Florida
	Tampa
	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
		Clinical Trials Office - H. Lee Moffitt Cancer Center and Reseach Institute	Ph:  800-456-7121
			Email: canceranswers@moffitt.org

Registry Information
Official Title		Pilot Neoadjuvant Study of ZD1839 (IRESSA®) as Single Agent Preoperative Therapy for Clinical Stage 1A and 1B (T1-2N0), II (T1-2N1, T3N0) and Selected IIIA (T3N1) Non-Small Cell Lung Cancer (NSCLC) with Molecular Correlates
Trial Start Date		2004-09-28
Trial Completion Date		2008-03-28 (estimated)
Registered in ClinicalTrials.gov		NCT00104728
Date Submitted to PDQ		2005-01-13
Information Last Verified		2008-08-08
NCI Grant/Contract Number		CA76292

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