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

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of paclitaxel albumin-stabilized nanoparticle formulation when given together with gemcitabine in treating patients with advanced metastatic solid tumors.

Detailed Description
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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.

Official Title
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Phase I Trial of Abraxane in Combination With Gemcitabine in Patients With Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Drug: paclitaxel albumin-stabilized nanoparticle formulation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: gemcitabine hydrochloride|1000 mg/m2 on days 1 and 8 of each 21 day cycle|
|Drug: paclitaxel albumin-stabilized nanoparticle formulation|260 mg/m2 to 340 mg/m2 (dose will depend on when subject enters the study). Paclitaxel will be given on day 1 of each 21 day cycle (every 3 weeks)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity (DLT) | Toxicity will be graded using the CTCAE version 3.0 and will be assessed on cycle one (21 days) | 21 days | 
| Maximum Tolerated Dose(MTD) | If greater than or equal to 2 of 6 patients (33%) experience a DLT, then that dose level will be considered to have excessive toxicity and will = MTD | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic Response to Treatment | Radiographic response will be measured and evaluated using RECIST criteria. | every 42 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gemzar, unspecified adult solid tumor, protocol specific, Paclitaxel, Abraxane, Gemcitabine, Phase I, Lineberger