A Randomized Phase II Study of Radiation Therapy, Pemetrexed and Carboplatin With or Without Cetuximab in Stage III Non-Small Cell Lung Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed non-small cell lung cancer (NSCLC),
including any of the following subtypes:

- Squamous cell carcinoma

- Adenocarcinoma (including bronchoalveolar cell carcinoma)

- Large cell anaplastic carcinoma (including giant cell and clear cell carcinoma)

- Stage IIIA OR selected stage IIIB disease*

- Any T, N2-3, M0 disease

- T3, N1-3, M0 disease allowed provided disease is unresectable

- T4, any N, M0 disease allowed provided T4 status cannot be determined due to
malignant effusion

- No T3, N0, M0 disease NOTE: *If the largest mediastinal lymph node is < 2 cm in
diameter by CT scan, a biopsy confirmation of mediastinal nodal involvement is
required

- Unresectable disease

- Contralateral mediastinal disease (N3) allowed provided all gross disease can be
encompassed within the radiation field in accordance with the homogeneity criteria

- Measurable disease, defined as ≥ 1 one-dimensional measurable lesion ≥ 20 mm by
conventional techniques OR ≥ 10 mm by spiral CT scan

- The following are not considered measurable disease:

- Bone lesions

- Leptomeningeal disease

- Ascites

- Pleural or pericardial effusion

- Abdominal masses not confirmed and followed by imaging techniques

- Cystic lesions

- Tumor lesions in a previously irradiated area

- No exudative, bloody, or cytologically positive malignant effusion

- Transudate, cytologically negative, non-bloody pleural effusion allowed provided
the tumor can be encompassed within a reasonable field of radiotherapy

- Pleural effusion detectable by chest CT scan but not by chest x-ray that is too
small to tap

- New pleural effusion appearing after thoracotomy or other invasive thoracic
procedure allowed

- No atelectasis of the entire lung

- No direct invasion of the vertebral body

- No scalene, supraclavicular, or contralateral hilar node involvement

- No distant metastases (M1) by fludeoxyglucose F18 positron emission tomography

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-1

Life expectancy

- Not specified

Hematopoietic

- Granulocyte count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

Hepatic

- Bilirubin < 1.5 times upper limit of normal (ULN)

- AST and ALT < 3 times ULN

- Alkaline phosphatase < 3 times ULN

Renal

- Creatinine clearance ≥ 45 mL/min

Cardiovascular

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

Other

- Not pregnant or nursing

- Weight loss ≤ 10% within the past 3 months

- No other active* malignancy except nonmelanoma skin cancer

- No ongoing or active infection

- No other uncontrolled illness

- No history of hypersensitivity to carboplatin, pemetrexed disodium, or a monoclonal
antibody NOTE: *Malignancy is not considered active if the patient has completed
treatment and has < 30% risk of relapse

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No concurrent filgrastim (G-CSF), pegfilgrastim, or sargramostim (GM-CSF) during
thoracic radiotherapy or as prophylaxis for myelosuppression

Chemotherapy

- No prior chemotherapy for NSCLC

- No other concurrent chemotherapy

Endocrine therapy

- No concurrent hormonal therapy except megestrol for appetite stimulation or
dexamethasone to prevent rash from pemetrexed disodium

Radiotherapy

- No prior radiotherapy to the chest

- No concurrent palliative radiotherapy

- No concurrent intensity modulated radiotherapy

Surgery

- See Disease Characteristics

- At least 2 weeks since prior formal exploratory thoracotomy

Other

- No prior therapy that directly targets the epidermal growth factor receptor pathway

- No concurrent combination antiretroviral therapy for HIV-positive patients