ABI-007 in Treating Patients With Chemotherapy-Naïve Stage IV Non-Small Cell Lung Cancer

An Open-Label, Phase I/II Trial Of ABI-007 (A CREMOPHOR® El-Free, Protein Stabilized, Nanoparticle Paclitaxel) Administered Weekly In Chemotherapy Naive Patients With Advanced Non-Small Cell Lung Cancer

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.

OBJECTIVES:

Primary

• 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.

Secondary

• 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.

DISEASE CHARACTERISTICS:

• 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 metastasis

• Measurable disease documented radiographically

• No evidence of active brain metastases or leptomeningeal involvement

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1 OR
• Karnofsky 80-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL

Hepatic

• 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)

Renal

• Creatinine ≤ 1.5 mg/dL

Other

• 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:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for metastatic disease
• More than 4 weeks since prior cytotoxic chemotherapy
• No concurrent doxorubicin
• No other concurrent taxanes
• No concurrent anthracyclines

Endocrine therapy

• Not specified

Radiotherapy

• 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

Surgery

• Not specified

Other

• 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:

  • Ritonavir
  • Saquinavir
  • Indinavir
  • Nelfinavir

• No concurrent anticonvulsants

• No other concurrent anticancer drugs

• No other concurrent investigational drugs