A Randomized Two-Period Crossover, Clinical Bioequivalence Study Comparing the Pharmacokinetics of Liposome Entrapped Paclitaxel Easy to Use (LEP-ETU) Formulation Versus Taxol® in Patients With Advanced Cancer
- Patients must have advanced histologically diagnosed non-hematological malignancy for
which there is no curative therapy and for which treatment with single agent
paclitaxel is appropriate in the opinion of the investigator.
- Patients must have a life expectancy of 12 weeks or more.
- Patients must have an ECOG Performance Status of 0-2.
- Patients must have recovered from acute toxicities of prior treatment. Specifically:
*4 or more weeks must have elapsed since receiving any investigational agent. *3 or
more weeks must have elapsed since receiving any radiotherapy, or treatment with
cytotoxic or biologic agents (6 weeks or more for mitomycin or nitrosureas). Chronic
treatment with non-investigational gonadotropin-releasing hormone analogs or other
hormonal or supportive care is permitted. *2 or more weeks must have elapsed since
any prior surgery or granulocyte-stimulating growth factor therapy.
- Patients must be in adequate condition as evidenced by the following clinical
laboratory values: *Absolute neutrophil count (ANC) ≥1,500/mm³, *Platelet count
≥100,000/mm³, *Hemoglobin ≥9.0 g/dL, *Albumin ≥3.0 g/dl, *Serum creatinine ≥2.0
mg/dL, *Total bilirubin 1.5 x the institutional upper limit of normal (ULN) or
greater. *Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
≤2.5 x ULN. In the case of known liver metastasis, ALT and AST ≤5 x ULN.
*Alkaline phosphatase (ALP) ≤2.5 x ULN. No ULN applies to alkaline phosphatase
in the case of known bone metastasis.
- Patients (male and female) must be willing to practice an effective method of
birth control during the study.
- Patients must be available for and able to comply with the study-specific blood
sampling requirements for pharmacokinetic evaluations.
- Patients or legal representative must understand the investigational nature of
this study and sign an Institutional Review Board (IRB) approved written
informed consent form prior to treatment.
- Active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer
- Any active infection requiring parenteral or oral antibiotic treatment; any use of
trimethoprim, including use for antimicrobial prophylaxis.
- Known infection with human immunodeficiency virus (HIV) or hepatitis virus.
- Active heart disease including myocardial infarction or congestive heart failure
within the previous 6 months, symptomatic coronary artery disease, or arrhythmias
currently requiring medication.
- Known or suspected active central nervous system metastasis. (Patients stable 8 weeks
after completion of treatment for central nervous system metastasis are eligible.)
- Impending or symptomatic spinal cord compression or carcinomatous meningitis.
- Having pre-existing clinically significant neuropathy (National Cancer Institute
Common Terminology Criteria for Adverse Events (NCI CTCAE) greater than or equal to
Grade 2 neuromotor or Grade 2 neurosensory) except for abnormalities due to cancer.
- Having known hypersensitivity to paclitaxel or liposomes.
- Receiving any agent that could interfere with LEP-ETU metabolism, including CYP3A4
inducers and inhibitors within 3 weeks prior to, or while receiving, study drug
(Please refer to http://medicine.iupui.edu/flockhart/ for a list of such agents).
- Requiring immediate palliative treatment of any kind including surgery and/or
- Female patients who are pregnant or breast feeding.
- Unwilling or unable to follow protocol requirements.
- Any condition which, in the Investigator's opinion, deems the patient an unsuitable
candidate to receive study drug.