RATIONALE: Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving cetuximab together with combination chemotherapy and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cetuximab together with paclitaxel, carboplatin, and radiation therapy works in treating patients with unresectable stage IIIA or stage IIIB 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: cetuximab  Drug: paclitaxel  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: monoclonal antibody therapy  Procedure: radiation therapy  Procedure: radiosensitization	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the feasibility of cetuximab when administered concurrently with paclitaxel, carboplatin, and radiotherapy, in terms of safety and compliance, in patients with unresectable stage IIIA or IIIB non-small cell lung cancer.

Secondary

• Determine the response rate (complete and partial) in patients treated with this regimen.
• Determine the overall survival (1- and 2-year survival rate and median survival) of patients treated with this regimen.
• Determine the time to disease progression (at 1 and 2 years) in patients treated with this regimen.
• Correlate epidermal growth factor receptor expression with the toxicity of this regimen and response, overall survival, and progression in these patients.

OUTLINE: This is a multicenter study.

• Cetuximab loading dose (week 1): Patients receive a loading dose of cetuximab IV over 2 hours on day 1.
• Concurrent cetuximab and chemoradiotherapy (weeks 2-8): Patients receive cetuximab IV over 1 hour, paclitaxel IV over 1 hour, and carboplatin IV over 30 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients undergo radiotherapy once daily on days 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, and 50-53.
• Consolidation therapy (weeks 9-17): Patients receive cetuximab IV over 1 hour on days 57, 64, 71, 78, 85, 92, 99, 106, and 113. Patients also receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on days 78 and 99. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed at 30 days, every 3 months for 2 years, every 4 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 84 patients will be accrued for this study within 1 year.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) of 1 of the following subtypes:
• Squamous cell carcinoma
• Adenocarcinoma (including bronchoalveolar cell)
• Large cell anaplastic carcinoma (including giant and clear cell carcinomas)
• Poorly differentiated/not otherwise specified NSCLC
• Stage IIIA (T1-2, N2, M0 or T3, N1-2, M0) or IIIB (T4, any N, M0 or any T, N2-3, M0)
• If the largest mediastinal node is < 2.0 cm in diameter and this is the basis for stage III disease, then at least 1 of the nodes must be cytologically or histologically positive
• Unresectable disease
• No totally resected tumors
• Tumors adjacent to a vertebral body allowed provided all gross disease can be encompassed in the radiation boost field and the boost volume is limited to < 50% of the ipsilateral lung volume
• Measurable disease
• Transudate, cytologically negative, non-bloody pleural effusions allowed provided the tumor can be encompassed within a reasonable field of radiotherapy
• Pleural effusions seen on a chest CT scan are allowed provided they are not visible on a chest x-ray and are too small to tap
• No asymptomatic or symptomatic brain metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL (transfusion independent)

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• SGOT or SGPT ≤ 3 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.5 times ULN

Renal

• Creatinine ≤ 2.0 mg/dL

Cardiovascular

• No significant history of cardiac disease
• No uncontrolled hypertension
• No unstable angina
• No uncompensated congestive heart failure
• No myocardial infarction within the past year
• No cardiac ventricular arrhythmias requiring medication
• LVEF normal by MUGA or echocardiogram

Pulmonary

• No history of interstitial pneumonitis
• No history of severe chronic obstructive pulmonary disease requiring 3 or more hospitalizations within the past year
• FEV_1 ≥ 1,200 cc
• No active pulmonary infection unresponsive to conventional antibiotics

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 weeks after study therapy
• Glucose ≤ 2 times ULN
• No more than 5% weight loss within the past 3 months
• No known allergy to murine proteins or Cremophor EL
• No neuropathy grade 2 or greater
• No other malignancy within the past 2 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other in situ cancers

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior drugs that target the epidermal growth factor receptor pathway
• No prior chimerized monoclonal antibody therapy
• No other concurrent immunotherapy
• No concurrent colony-stimulating factors (i.e., filgrastim [G-CSF] and sargramostim [GM-CSF])
• Concurrent epoetin alfa allowed

Chemotherapy

• No prior systemic chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy except hormones for non-disease-related conditions (e.g., insulin for diabetes) or steroids for acute symptom management, adrenal failure, septic shock, or as antiemetics

Radiotherapy

• No prior thoracic or neck radiotherapy
• No concurrent intensity-modulated radiotherapy

Surgery

• Recovered from prior exploratory thoracotomy
• No prior surgical resection of the present cancer

Other

• More than 30 days since prior participation in another clinical trial
• No concurrent participation in another clinical trial
• No other concurrent anticancer therapy
• No amifostine during or for 3 months after study radiotherapy

Texas
      Arlington Cancer Center - Arlington, Arlington,  Texas,  76012,  United States; Recruiting

Study chairs or principal investigators

George R. Blumenschein, MD,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000352163; RTOG-0324; NCT00081302
Record last reviewed:  February 2005
Last Updated:  April 5, 2005
Record first received:  April 7, 2004
ClinicalTrials.gov Identifier:  NCT00081302
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08