Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Gemcitabine in Treating Patients With Advanced Metastatic Solid Tumors

OBJECTIVES:

Primary

• Determine the dose-limiting toxicity and maximum tolerated dose of paclitaxel albumin-stabilized nanoparticle formulation (Abraxane) in combination with gemcitabine hydrochloride in patients with advanced metastatic solid tumors.

Secondary

• Evaluate the efficacy of this regimen in these patients.

OUTLINE: This is a dose-escalation study of paclitaxel albumin-stabilized nanoparticle formulation (Abraxane).

Patients receive paclitaxel albumin-stabilized nanoparticle formulation (Abraxane) IV over 30 minutes on day 1 followed by gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of paclitaxel albumin-stabilized nanoparticle formulation (Abraxane) 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. Up to 10 additional patients may be treated at the MTD.

After completion of study treatment, patients are followed at 30 days.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed solid tumors

• Advanced metastatic disease
• Measurable or evaluable disease
• Must meet 1 of the following criteria:

• Failed prior standard therapy
• Not a candidate for standard therapy
• Has a disease for which there is no defined standard therapy
• No symptomatic brain metastases

PATIENT CHARACTERISTICS:

• ECOG functional status 0-2
• Life expectancy ≥ 8 weeks
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count > 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL
• Bilirubin normal
• Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 60 mL/min
• AST and ALT ≤ 2.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• No prior anaphylactic reaction or severe allergic reaction to paclitaxel, docetaxel, or gemcitabine hydrochloride
• No active infectious process that will require treatment with antibiotics for > 4 weeks
• No uncontrolled congestive heart failure
• No symptomatic coronary artery disease or heart block
• No myocardial infarction within the past 3 months
• No peripheral neuropathy ≥ grade 2 from any cause

PRIOR CONCURRENT THERAPY:

• More than 3 weeks since prior chemotherapy, radiotherapy, or any other treatment
• No prior radiotherapy to > 25% of bone marrow
• No prior nitrosoureas
• No more than 6 prior courses of alkylating agents
• No more than 2 prior courses of mitomycin C
• No more than 3 prior courses of cytotoxic therapy for metastatic disease
• No concurrent filgrastim (G-CSF), pegfilgrastim, or sargramostim (GM-CSF) during study course 1