RATIONALE: Drugs used in chemotherapy, such as ABI-007, work in different ways to stop tumor
cells from dividing so they stop growing or die.
PURPOSE: This phase I/II trial is studying the side effects and best dose of ABI-007 and to
see how well it works in treating patients with stage IV non-small cell lung cancer.
- Determine the maximum tolerated dose and dose-limiting toxicity of paclitaxel
(albumin-stabilized Nanoparticle formulation) (ABI-007) in patients with
chemotherapy-naïve stage IV non-small cell lung cancer.
- Determine the antitumor activity of this drug in these patients.
- Determine the safety and tolerability of this drug in these patients.
- Determine the time to disease progression in patients treated with this drug.
- Determine duration of response in patients treated with this drug.
- Determine survival of patients treated with this drug.
OUTLINE: This is an open-label, dose-escalation study.
- Phase I: Patients receive paclitaxel (albumin-stabilized Nanoparticle formulation)
(ABI-007) IV on days 1, 8, and 15. Courses repeat every 28 days in the absence of
disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of ABI-007 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6
patients experience dose-limiting toxicity.
- Phase II: Patients receive ABI-007 as above at the MTD (determined in phase I).
Patients are followed monthly for 6 months and then every 3 months for 1.5 years.
PROJECTED ACCRUAL: A total of 64 patients will be accrued for this study.
- Histologically or cytologically confirmed stage IV non-small cell lung cancer
- Evidence of inoperable local recurrence or metastasis
- Bone metastases or other nonmeasurable disease may not be only evidence of
- Measurable disease documented radiographically
- No evidence of active brain metastases or leptomeningeal involvement
- 18 and over
- ECOG 0-1 OR
- Karnofsky 80-100%
- More than 12 weeks
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9 g/dL
- AST and ALT ≤ 2.5 times upper limit of normal (ULN)
- Bilirubin normal
- Alkaline phosphatase ≤ 2.5 times ULN (unless due to bone metastases and there is no
radiologic evidence of hepatic metastases)
- Creatinine ≤ 1.5 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception for 1 month before and
during study participation
- No prior allergy or hypersensitivity to study drug
- No other concurrent active malignancy
- No pre-existing peripheral neuropathy grade 1 or greater
- No other concurrent clinically significant illness
- No concurrent serious medical risk factor involving any of the major organ systems
that would preclude study participation
PRIOR CONCURRENT THERAPY:
- Not specified
- No prior chemotherapy for metastatic disease
- More than 4 weeks since prior cytotoxic chemotherapy
- No concurrent doxorubicin
- No other concurrent taxanes
- No concurrent anthracyclines
- Not specified
- At least 3 weeks since prior radiotherapy to a major bone marrow-containing area
- More than 4 weeks since prior radiotherapy except to a non-target lesion
- Prior radiotherapy to a target lesion allowed provided there has been clear
progression of the lesion since completion of radiotherapy
- Not specified
- Prior epidermal growth factor-targeted therapy allowed
- More than 4 weeks since prior investigational drugs
- No concurrent enrollment in another clinical trial in which investigational drugs are
administered or investigational procedures are performed
- No concurrent treatment with any of the following:
- No concurrent anticonvulsants
- No other concurrent anticancer drugs
- No other concurrent investigational drugs