Gene Expression Levels in Predicting Treatment Response in Patients With Stage IV Non-small Cell Lung Cancer

PRIMARY OBJECTIVES:

I. To describe the association between baseline gene expression levels at the protein and
messenger ribonucleic acid (mRNA) level and best treatment response after two cycles of
single-agent or multi-agent chemotherapy

SECONDARY OBJECTIVES:

I. To describe changes in protein and mRNA levels of ribonucleotide reductase M1 (RRM1),
thymidylate synthetase (TS), and excision repair cross-complementing rodent repair
deficiency, complementation group 1 (ERCC1) in serial biopsies obtained from patients being
treated with gemcitabine (gemcitabine hydrochloride), pemetrexed (pemetrexed disodium), and
platinum.

II. To describe the association between changes in marker levels and changes in tumor
diameters.

TERTIARY OBJECTIVES:

I. To explore the relationship between marker levels in circulating tumor cells and solid
tumor specimens.

II. To explore the relationship between marker levels in viable peripheral blood mononuclear
cells (PBMCs), circulating tumor cells, and tumor specimens.

III. Should sufficient amounts and numbers of tumor specimens remain after these analyses,
they will be used to assess if other genes implicated in non-small cell lung cancer (NSCLC)
outcome and response to treatment might be useful as prognostic or predictive markers for
patient outcome.

OUTLINE:

Patients receive 1 of 3 chemotherapy regimens at the discretion of the primary oncologist,
including docetaxel intravenously (IV) on day 1, pemetrexed disodium IV on day 1, or
gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 3 weeks for 2 courses
in the absence of disease progression or unacceptable toxicity. After course 2, patients may
continue treatment off-study at the discretion of the treating physician.

After completion of study treatment, patients are followed up for 12 months.

Inclusion Criteria:

- Patients with advanced stage NSCLC who are candidates for single or multi-agent
first-line therapy.

- Second-line or higher therapy for any patients with NSCLC with performance status (PS)
0-2

- Maintenance therapy for patients after completion of four cycles of dual-agent
platinum-based chemotherapy

- Stage IV, histologically or cytologically confirmed NSCLC; confirmation may be
obtained with the first protocol-specified tumor biopsy

- White blood cell count > 3000/mm^3

- Platelet count > 100,000/mm^3

- Hemoglobin > 9.0 g/dl

- A tumor lesion that can be safely biopsied as judged by the treating oncologist and
physician performing the procedure and has not been radiated

- At least one unidimensionally measurable tumor lesion >= 1 cm in longest diameter
using spiral CT (>= 2 cm in longest diameter by any other technique) that has not been
radiated and is not located in a bone

- Performance status 0-2 by Eastern Cooperative Oncology Group criteria

- Life expectancy of >= 3 months

- Able to understand and sign the informed consent document

Exclusion Criteria:

- Therapy that does not include cisplatin, carboplatin, gemcitabine, and/or pemetrexed

- Concomitant medical or psychiatric illness that is likely to interfere with a
reasonably safe execution of the treatment plan

- Concomitant malignancy other than NSCLC that requires active therapy; prior
malignancies are allowed as long as the disease is controlled and does not require
ongoing therapy of any kind; prior therapy must have concluded at least 1 year before
treatment initiation on this protocol; exceptions are non-melanoma skin cancer,
prostate cancer and prostatic intraepithelial neoplasia (PIN) treated with local
intervention and deemed cured, cervical cancer and carcinoma in situ (CIS) treated
with local intervention and deemed cured, and laryngeal cancer and CIS treated with
local intervention and deemed cured

- Carcinomatous meningitis

- Uncontrolled central nervous system (CNS) disease

- The time interval between CNS radiation, whole brain radiation, spinal cord radiation,
or radiosurgery, and initiation of protocol specified chemotherapy must be at least 1
week

- Malignant pleural, pericardial, or peritoneal effusion if it is the only site of
disease activity; i.e., if no other measurable tumor lesions exist

- Coagulopathy or anticoagulation therapy that cannot be safely corrected or interrupted
for tumor biopsy

- Significant hepatic dysfunction, renal dysfunction, or metabolic derangement that
precludes full-dose chemotherapy at the specified starting doses

- Concomitant treatment with chemotherapeutic agents for diseases other than malignancy

- Pregnancy or lactation