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

Alternate Title

Neoadjuvant Chemoradiotherapy With or Without Gefitinib in Treating Patients With Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Closed	19 and over	NCI	UAB-0162 UAB-F020730006, ZENECA-ZD1839US-0207, AVENTIS-GIA-12139, NCT00062270

Objectives

Phase I:

1. Determine the tolerability and toxicity of gefitinib in combination with chest radiotherapy in patients with stage IIIA or stage IIIB non-small cell lung cancer.

Phase II:

1. Compare the pathologic response (complete response and rate of downstaging) in patients treated with neoadjuvant chemoradiotherapy with vs without gefitinib.
2. Compare the feasibility and toxicity profile of these regimens in these patients.
3. Compare the resection rates, time to progression, and overall survival of patients treated with these regimens.
4. Correlate the percent decline in the fludeoxyglucose F 18 standardized uptake value as measured by position emission tomography with pathologic response at resection, time to progression, and overall survival in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed non-small cell lung cancer
  • Stage IIIA (T1-3, N2)
    • Positive (pathological) ipsilateral mediastinal node
  • Selective stage IIIB meeting all of the following criteria:
    • No pleural/pericardial effusion or superior vena cava syndrome
    • T4 due to invasion of carina, trachea, or mediastinal structures
    • Mediastinal N3 nodes (without supraclavicular or cervical adenopathy)



• Proof of N2 or N3 status requires surgical staging of the mediastinum (mediastinoscopy, mediastinotomy, or exploration)



• Expression of epidermal growth factor receptor (at least 1+) by immunohistochemistry



• Measurable disease by contrast CT scan allowed



• No bronchoalveolar cell carcinoma



• No prior diagnosis of lung cancer

Prior/Concurrent Therapy:

Biologic therapy

• No concurrent growth factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) during chemotherapy

Chemotherapy

• No prior chemotherapy for lung cancer

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for lung cancer

Surgery

• Recovered from prior major surgery
• No concurrent opthalmic surgery

Other

• More than 30 days since prior unapproved or investigational drugs
• No concurrent use of the following drugs:
  • Phenytoin
  • Carbamazepine
  • Barbiturates
  • Rifampin
  • Phenobarbital
  • Hypericum perforatum (St. John's Wort)
  • Warfarin
• No concurrent retinoids

Patient Characteristics:

Age

• 19 and over

Performance status

• ECOG 0-1 (0-2 if albumin is at least 0.85 times lower limit of normal and weight loss within 3 months before diagnosis is no greater than 10%)

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 150,000/mm³
• Hemoglobin at least 10 g/dL

Hepatic

• Bilirubin normal
• AST and ALT no greater than 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2 times ULN
  • Alkaline phosphatase between 1.5-2 times ULN requires a negative bone scan for metastatic bone disease

Renal

• Creatinine no greater than 1.4 mg/dL

  OR

• Creatinine clearance at least 60 mL/min

Cardiac

• No myocardial infarction within the past 3 months
• No active angina
• No unstable heart rhythms
• No congestive heart failure

Pulmonary

• Postresection predicted FEV₁% greater than 35%
  • Predicted FEV₁% is defined as FEV₁% times percent perfusion to uninvolved lung from quantitative lung V/Q scan report

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 6 weeks after study treatment
• No other uncontrolled medical illness
• No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix
• No grade 2 or greater peripheral neuropathy
• No concurrent ocular inflammation or infection
• No prior severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
• No known severe hypersensitivity reaction to gefinitib or any of its excipients
• No prior severe allergic reaction to platinum-containing compounds or mannitol

Expected Enrollment

A total of 43-80 patients (3-6 patients for phase I and 40-74 patients [20-37 per treatment arm] for phase II) will be accrued for this study.

Outline

• Phase I: This is an open-label, nonrandomized study.
  • Induction: Patients receive cisplatin IV over 60 minutes on day 1 and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for a total of 2 courses in the absence of disease progression or unacceptable toxicity.
  
  
  
  • Consolidation: Within 3-4 weeks after the completion of induction therapy, patients undergo radiotherapy once daily 5 days a week for 5 weeks and receive oral gefitinib once daily concurrently.

    A cohort of 3-6 patients receives consolidation chemoradiotherapy. If 2 of 6 patients experience dose-limiting toxicity, gefitinib is deleted from consolidation therapy in phase II arm II.

  
  
  
  • Surgery: Patients without disease progression after consolidation therapy undergo thoracotomy within 3-5 weeks after consolidation.
  
  
  
  • Maintenance: Beginning 2-4 weeks after surgery, patients receive oral gefitinib once daily for 6 months in the absence of disease progression.
  
  
  



• Phase II: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.
  • Arm I: Patients receive induction and consolidation therapy (with the exception of gefitinib) as in phase I. Patients also receive docetaxel IV over 60 minutes concurrently with radiotherapy during consolidation. Patients undergo surgery as in phase I.
  
  
  
  • Arm II: Patients receive therapy (including gefinitib) as in phase I. Patients also receive docetaxel IV over 60 minutes concurrently with radiotherapy during consolidation.
  
  
  

Patients are followed every 6-8 weeks for the first 12 months and then every 4-6 months thereafter.

Trial Contact Information

Trial Lead Organizations

UAB Comprehensive Cancer Center

Francisco Robert, MD, FACP, Protocol chair		Ph: 205-934-5077

Registry Information
Official Title		Neoadjuvant Chemoradiotherapy (Gemcitabine/Cisplatin and Taxotere) With or Without Co-Administration of ZD 1839 (Iressa) for Stage IIIA (N2) and Selective Stage IIIB Non-Small Cell Lung Cancer: Phase I-II Study
Trial Start Date		2003-05-18
Registered in ClinicalTrials.gov		NCT00062270
Date Submitted to PDQ		2003-05-01
Information Last Verified		2004-07-26
NCI Grant/Contract Number		P30-CA13148

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