RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib and radiation therapy with combination chemotherapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining erlotinib and radiation therapy with combination chemotherapy in treating patients who have inoperable stage III non-small cell lung cancer.

Condition	Treatment or Intervention	Phase
stage IIIA non-small cell lung cancer stage IIIB non-small cell lung cancer Squamous Cell Lung Cancer large cell lung cancer Adenocarcinoma of the Lung Bronchoalveolar Cell Lung Cancer	Drug: carboplatin  Drug: cisplatin  Drug: docetaxel  Drug: erlotinib  Drug: etoposide  Drug: paclitaxel  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy  Procedure: radiation therapy  Procedure: radiosensitization	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of erlotinib that can be administered with chest radiotherapy in combination with cisplatin and etoposide or carboplatin and paclitaxel in patients with inoperable stage III non-small cell lung cancer.
• Determine the dose-limiting toxicity of these regimens in these patients.
• Assess the clinical response (complete response, partial response, progressive disease, or stable disease) in patients treated with these regimens.
• Determine levels of tumor epidermal growth factor expression in patients treated with these regimens.

OUTLINE: This is a multicenter, dose-escalation study of erlotinib. Patients are assigned to 1 of 2 treatment groups.

• Group 1: Patients receive cisplatin IV over 2 hours on days 1, 8, 29, and 36; etoposide IV over 1 hour on days 1-5 and 29-33; and oral erlotinib once daily on days 1-49. Patients undergo concurrent radiotherapy 5 days a week for 7 weeks beginning on day 1. Patients receive consolidation therapy comprising docetaxel IV over 1 hour on days 50, 71, and 92. Some patients may also receive oral erlotinib once daily on days 50-112.
• Group 2: Patients receive induction chemotherapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1 and 21. Patients receive consolidation therapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 43, 50, 57, 64, 71, 78, and 85 and oral erlotinib once daily on days 43-91. Patients undergo radiotherapy concurrently with consolidation therapy 5 days a week for 7 weeks beginning on day 43. In both groups, cohorts of 3-6 patients receive escalating doses of erlotinib during concurrent chemoradiotherapy until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 6 patients experience dose-limiting toxicity. At least 12 patients from each group are treated at the MTD.

Patients are followed at 8 weeks.

PROJECTED ACCRUAL: A total of 24-48 patients (12-24 per treatment group) will be accrued for this study within 6-12 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed non-small cell lung cancer
• Squamous cell carcinoma
• Adenocarcinoma (including bronchoalveolar)
• Large cell carcinoma (including giant and clear cell carcinomas)
• Stage IIIA (T1 or T2, N2) or IIIB disease not amenable to resection or surgery
• T3, N2 or T4, N0-N2 disease also allowed if based on the closeness to the carina, invasion of the mediastinum, or invasion of the chest wall
• T3, N0-N1 disease allowed provided the disease is not amenable for surgical resection
• No M1 disease
• No disease invasion of a vertebral body
• Tumors adjacent to a vertebral body allowed provided all gross disease can be encompassed in the radiotherapy boost field and there is no bone invasion
• Contralateral mediastinal disease (N3) allowed if all gross disease can be encompassed in the radiotherapy boost field
• Pleural effusion that is transudative, cytologically negative, and non-bloody allowed if the tumor can be encompassed in a reasonable field of radiotherapy
• No exudative, bloody, or cytologically malignant effusions
• Effusions present on CT scans but not on chest x-ray (CXR) and too small for thoracentesis are allowed
• Measurable or evaluable disease
• Pleural effusions are not considered measurable or evaluable
• Measurable disease is defined as any mass in 2 perpendicular diameters by CXR, CT scan, or MRI
• Evaluable disease includes lesions apparent on CXR or CT scan that are:
• Ill-defined masses associated with post-obstructive changes
• Mediastinal or hilar adenopathy measurable in only one dimension

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1 OR
• Karnofsky 70-100%

Life expectancy

• More than 6 months

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin normal
• AST and ALT no greater than 1.5 times upper limit of normal (ULN) and alkaline phosphatase normal OR
• AST and ALT normal and alkaline phosphatase no greater than 2.5 times ULN

Renal

• Creatinine normal OR
• Creatinine clearance at least 50 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Ophthalmic

• No history of cornea abnormalities (e.g., dry-eye syndrome, Sjögren's syndrome)
• No congenital abnormality (e.g., Fuch's dystrophy)
• No abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal-Rose)
• No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test)

Gastrointestinal

• No gastrointestinal tract disease resulting in the inability to take oral medications
• No required IV alimentation
• No peptic ulcer disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of allergy to compounds of similar chemical or biologic composition to erlotinib or other study agents
• No significant traumatic injury within the past 21 days
• No other uncontrolled concurrent illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other active malignancy within the past 6 months except non-melanoma skin cancer

PRIOR CONCURRENT THERAPY: Biologic therapy

• No concurrent colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF]) with radiotherapy

Chemotherapy

• No prior chemotherapy for lung cancer

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• No prior chest radiotherapy

Surgery

• See Disease Characteristics
• At least 7 days since prior mediastinoscopy
• More than 3 weeks since prior formal exploratory thoracotomy
• More than 3 weeks since prior major surgery
• No prior surgical procedures affecting absorption

Other

• No prior epidermal growth factor receptor-targeting therapies
• No other concurrent investigational or commercial agents or therapies directed at malignancy
• No concurrent combination antiretroviral therapy for HIV-positive patients

Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153-5589,  United States; Recruiting
      Central Illinois Hematology Oncology Center, Springfield,  Illinois,  62701,  United States; Recruiting
      Decatur Memorial Hospital Cancer Care Institute, Decatur,  Illinois,  62526,  United States; Recruiting
      Evanston Northwestern Health Care - Evanston Hospital, Evanston,  Illinois,  60201-1781,  United States; Recruiting
      Ingalls Cancer Care Center at Ingalls Memorial Hospital, Harvey,  Illinois,  60426,  United States; Recruiting
      Oncology/Hematology Associates of Central Illinois, P.C., Peoria,  Illinois,  61615-7828,  United States; Recruiting
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States; Recruiting
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States; Recruiting
Michigan
      Oncology Care Associates, P.L.L.C., Saint Joseph,  Michigan,  49085,  United States; Recruiting
Wisconsin
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226,  United States; Recruiting

Study chairs or principal investigators

Ann M. Mauer, MD,  Study Chair,  University of Chicago Cancer Research Center   

Study ID Numbers:  CDR0000069474; UCCRC-11432B; NCI-5411; NCT00042835
Record last reviewed:  May 2004
Last Updated:  April 4, 2005
Record first received:  August 5, 2002
ClinicalTrials.gov Identifier:  NCT00042835
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08