Carboplatin With Either Paclitaxel Poliglumex or Paclitaxel in Treating Women With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer

OBJECTIVES:

Primary

- Compare the overall survival of patients with chemotherapy-naïve stage IIIB or IV or
recurrent non-small cell lung cancer treated with paclitaxel poliglumex and carboplatin
vs paclitaxel and carboplatin.

Secondary

- Compare the progression-free survival of women treated with these regimens.

- Compare the disease control in women treated with these regimens.

- Compare the clinical benefit in women treated with these regimens.

- Compare the response rate in women treated with these regimens.

- Compare the quality of life of women treated with these regimens.

- Compare the safety and tolerability in women treated with these regimens.

OUTLINE: This is a multicenter study.

Patients are stratified according to age (≥ 60 vs < 60 years old), geographical location
(United States of America, Canada, or Australia vs the rest of the world), extent of disease
(independent of brain metastases, i.e., brain metastases are not considered in determining
extent of disease) (intrathoracic disease only vs extrathoracic disease), and ECOG
performance status (0 or 1 vs 2). Patients will be randomized to 1 of 2 treatment arms.

- Arm I: Patients receive paclitaxel poliglumex IV over 10 minutes followed by
carboplatin IV over 30 minutes on day 1.

- Arm II: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30
minutes on day 1.

In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease
progression or unacceptable toxicity.

Quality of life is assessed at baseline, before each course, and at the completion of study
treatment by the Pain Assessment Patient Questionnaire, the Pulmonary Symptom Index, and the
Functional Assessment of Cancer Therapy- Lung Cancer Subscale (FACT-LCS) (only in countries
in which a validated translation is currently available).

After completion of study therapy, patients are followed at least monthly.

DISEASE CHARACTERISTICS:

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

- Cytologic specimens obtained by brushings, washings, or needle aspiration of a
defined lesion or from a pleural effusion are acceptable; sputum cytology alone
is not acceptable for determining cell type

- Must meet one of the following criteria:

- Recurrent disease following completion of radiation or surgery

- Stage IIIB disease and not a candidate for combined modality therapy (primary
radiation therapy or surgery)

- Stage IV disease

- Patients may have either measurable or nonmeasurable disease according to RECIST
criteria

- Baseline estradiol > 30 pg/mL

- Patients on hormone replacement therapy are eligible provided baseline estradiol
> 30 pg/mL

- Patients with known brain metastases must have received standard antitumor treatment
(e.g. whole brain radiation, stereotactic radioablation, or surgery) for their CNS
metastases as defined by the site's institutional standards

- Neurologic function must have been stable for 2 weeks before randomization and
patients must either be off steroid therapy for their brain metastases or on a
tapering regimen

- Patients must have recovered from therapy for their brain metastases with no
evidence of significant unstable neurological symptoms within the 4 weeks before
study randomization

- No evidence of small cell carcinoma, carcinoid, or mixed small cell/non-small cell
histology

PATIENT CHARACTERISTICS:

- Female

- ECOG performance score 0-2

- Life expectancy ≥ 12 weeks

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 10 g/dL (may be achieved with transfusion)

- Creatinine ≤ 1.5 times upper limit of normal (ULN)

- Total bilirubin ≤ 1.5 times ULN (CTC grade 1) (patients with Gilbert syndrome or
other hereditary bilirubin defects may be included regardless of bilirubin levels)

- SGOT and SGPT ≤ 2.5 times ULN (CTC grade 0 or 1) (5 times ULN [CTC grade 0 to 2] if
due to liver metastases)

- Alkaline phosphatase ≤ 2.5 times ULN except for elevated alkaline phosphatase with
laboratory documentation that demonstrates bone origin

- No pregnant women or nursing mothers

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 6 months after study
participation

- No known hypersensitivity to study drugs or excipients

- Meets all of the following criteria:

- No weight loss > 10% in previous 6 months

- Lactate dehydrogenase (LDH) ≤ 600 IU/L (central laboratory) regardless of weight
loss

- LDH ≤ 400 IU/L (central laboratory) and no weight loss ≥ 5% in previous 6 months

- BMI ≤ 35

- No concurrent primary malignancies except for carcinoma in situ or non-melanoma skin
cancer

- No neuropathy grade 2 or greater

- No clinically significant active infection for which active therapy is underway

- No unstable medical conditions including unstable angina or myocardial infarction
within the past 6 months

- Patients with evidence of cardiac conduction abnormalities are eligible if their
cardiac status is stable

- No circumstance that would preclude completion of the study or the required follow-up

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered from major surgery

- At least 7 days since prior local palliative radiotherapy

- At least 30 days since prior radiation therapy with curative intent

- At least 4 weeks since prior investigational therapy, unless local requirements are
more stringent

- No prior systemic chemotherapy for the treatment of lung cancer, including systemic
radiosensitizers used to treat brain metastases or any biologic agents

- No concurrent non-protocol-specified systemic antitumor therapy

- No concurrent amifostine, investigational agents, other cytotoxic agents for this
disease

- No concurrent radiotherapy (with the exception of radiotherapy for brain or bone
metastases for palliative purposes or radiotherapy for a condition other than NSCLC
that was ongoing at the time of randomization)

- Patients receiving palliative radiotherapy (treatment for symptomatic metastatic
disease) may be treated while on study