A Randomized Phase II Study of Gemcitabine and Carboplatin With or Without AZD2171 as First-Line Therapy in Advanced Non-Small Cell Lung Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

- Squamous cell histology allowed

- No mixed histology with small cell component

- Stage IIIB (with pleural effusion) or stage IV disease

- Presence of peritoneal or pericardial effusion alone in the absence of cytologic
evidence is not allowed

- Measurable disease, defined as ≥ 1 lesion with longest diameter ≥ 2.0 cm by
conventional techniques OR ≥ 1.0 cm by spiral CT scan

- If the only site of measurable disease was previously irradiated, progressive
disease must be evident

- Ineligible for bevacizumab therapy

- No symptomatic, untreated, or uncontrolled CNS metastases

- CNS metastases treated with whole-brain radiation (WBRT) allowed 4 weeks after
completion of WBRT

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Life expectancy ≥ 12 weeks

- Absolute neutrophil count ≥ 1,500/mm^3

- Hemoglobin ≥ 9 g/dL

- Platelet count ≥ 100,000/mm^3

- Bilirubin ≤ 3 times upper limit of normal (ULN)

- ALT and AST ≤ 3 times ULN (5 times ULN if liver involvement)

- Alkaline phosphatase ≤ 5 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective nonhormonal contraception

- No proteinuria ≥ 1+

- No uncontrolled blood pressure (BP), defined as systolic BP > 150 mm Hg and/or
diastolic BP > 100 mm Hg in spite of adequate antihypertensive therapy

- No impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of AZD2171 (e.g., ulcerative disease, uncontrolled
nausea, vomiting, or diarrhea, malabsorption syndrome, or small bowel resection)

- No seizure disorder

- No significant traumatic injury within 4 weeks prior to study entry

- No second primary malignancy except any of the following:

- Carcinoma in situ of the cervix

- Nonmelanoma skin cancer

- Prior malignancy diagnosed and definitively treated ≥ 5 years ago with no
subsequent evidence of recurrence

- History of low-grade (Gleason score ≤ 6) localized prostate cancer even if
diagnosed < 5 years prior to registration

- Treated stage I breast cancer ≤ 5 years prior to registration

- No uncontrolled intercurrent illness, including, but not limited to, any of the
following:

- Ongoing or active infection

- Significant pulmonary symptoms at baseline due to disease

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situation that would limit compliance with study
requirements

- Baseline hemoptysis

- Cavitating lesions

- No QTc prolongation > 500 msec or other significant ECG abnormality within the past
14 days

- No New York Heart Association class III or IV disease

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior chemotherapy for advanced lung cancer

- Neoadjuvant or adjuvant therapy for lung cancer within the past 12 months
allowed

- More than 12 months since prior immunotherapy and biologic therapy

- More than 4 weeks since prior radiotherapy (2 weeks for palliative radiotherapy to
skeletal metastases)

- At least 2 weeks since prior WBRT

- No radiotherapy to ≥ 25% of bone marrow

- No major surgery (i.e., laparotomy) or open biopsy within 4 weeks prior to study
entry (2 weeks for minor surgery)

- Insertion of a vascular access device not considered major or minor surgery

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent grapefruit or grapefruit juice during AZD2171 treatment

- No concurrent drugs or biologics with proarrhythmic potential

- Concurrent palliative radiotherapy to nontarget sites (i.e., painful pre-existing
bony metastasis) allowed with AZD2171 (chemotherapy is held until completion of
radiotherapy)