A Randomized, Placebo-Controlled Phase II Clinical Trial of Combination Erlotinib (Tarceva) and Celecoxib (Celebrex) Versus Erlotinib (Tarceva)/Placebo in Advanced Non-Small Cell Lung Cancer Patients

Inclusion Criteria

Inclusion

- Pathologically proven NSCLC, stage IIIB (defined as: with pleural effusion or
recurrence after mediastinal radiation and chemotherapy) or IV

- Available tumor tissue for mutation screening

- Measurable stage IIIb or IV disease by RECIST guidelines

- ECOG performance status of 0 or 1

- Progressive disease despite >= 1 prior chemotherapy regimens as standard of care or
subject's refusal or inability to receive standard chemotherapy

- Normal renal function (defined as serum creatinine =< 2mg/dl)

- Normal liver function (defined as serum total bilirubin =< 1.5, and serum
transaminases =< 2.5X the upper limits of normal [ULN]); if liver metastases are
present, serum transaminases > 5X the ULN

- No evidence of coagulopathy (defined as PT and/or PTT =< 1.5X ULN or platelets >=
100,000)

- No evidence of leukopenia (defined as absolute neutrophil count >= 1,500 mm^3)

- Negative pregnancy test prior to initiation of treatment and adequate contraception
throughout treatment

Exclusion

- Cytotoxic chemotherapy agents within 4 weeks of initiating treatment; all toxicities
must be recovered to baseline or NCI CTCAE v3.0 Grade 1 from all acute effects of
prior cancer treatment, except alopecia or any clinically insignificant effect, prior
to study initiation

- Evidence of NYHA class III or greater cardiac disease, history of myocardial
infarction, cerebral vascular accident, symptomatic ventricular arrhythmia, or
symptomatic conduction abnormality

- Non-cytoxic therapy within 2 weeks of initiating treatment ; all toxicities must be
recovered to baseline or NCI CTCAE v3.0 Grade 1 from all acute effects of prior
cancer treatment, except alopecia or any clinically insignificant effect, prior to
study initiation

- Prior radiotherapy to target lesions is not permitted unless completed more than 4
weeks prior to treatment within the study and that there has been documented
progression at these sites (Radiotherapy to non-target lesions is permitted within 2
weeks of study entry provided all acute effects of the radiotherapy have resolved at
least grade 1)

- Comorbid disease or a medical condition that would impair the ability of the subject
to receive or comply with the study protocol

- Prior malignancy within the last 3 years with the exception of non-melanoma skin
cancer or cervical cancer in situ

- Hypersensitivity of erlotinib or celecoxib or to any of the excipients of these
products

- Hypersensitivity to sulfonamides, aspirin or other NSAIDS

- Prior history of EGFR inhibitor for the treatment of cancer

- Previous history of gastrointestinal ulceration, bleeding or perforation

- Concurrent use of COX-2 inhibitors or other NSAIDS (For subjects on NSAIDS prior to
study initiation, cessation of the drug for 72 hours prior to study entry is
required)

- Chronic or concurrent use of steroids (topical steroids are acceptable if medically
indicated)

- Subjects who require treatment with fluconazole or lithium

- Any evidence of clinically active interstitial lung disease (patients with chronic
stable radiographic changes who are asymptomatic need not be excluded)

- Renal insufficiency (defined as serum creatinine > 2 mg/dl)

- Liver insufficiency (defined as serum total bilirubin > 1.5, or serum transaminases >
2.5C the upper limits of normal [ULN]); if liver metastases are present, serum
transaminases > 5X the ULN

- Coagulopathy (defined as PT and/or PTT > 1.5X ULN or platelets < 100,000)

- Leukopenia (defined as absolute neutrophil count < 1,500/mm^3)

- Pregnancy or inadequate contraception

- Lactating females

- Active CNS metastasis (stable, treated CNS metastasis acceptable)