Study of Liposome Encapsulated Mitoxantrone (LEM) in Patients With Advanced Cancer
Liposome entrapped mitoxantrone (LEM) is a mixture of commercially available mitoxantrone HCL (Novantrone) and a combination of lyophilized lipids. Mitoxantrone, the active agent in the investigational formulation, is a currently marketed chemotherapeutic agent. The rationale for development of liposomal formulations is primarily that of improving the safety profile of the drug, which may permit dose intensification and/or an increase in the cumulative dose that may be administered, resulting in enhanced efficacy.
LEM will be given to patients with advanced solid tumors to determine the dose of drug these patients can tolerate. Patients will receive intravenous LEM every 21 days until the disease progresses or toxicity occurs requiring treatment discontinuation. Anti-tumor effects of LEM will be assessed and patients will be evaluated for safety and tolerability.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Study Start Date:||August 2001|
|Estimated Study Completion Date:||June 2004|
OBJECTIVES: I. Determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of LEM.
II. Measure the blood pharmacokinetics of LEM following IV administration.
III. Observe any anti-tumor effects of LEM.
PROTOCOL OUTLINE: This is an open-label study for patients with advanced and/or metastatic, histologically-documented solid tumors considered to be unresponsive to available conventional treatment.
LEM will be administered IV over 45 minutes. At least three patients will be studied at each dose level and at least three patients will complete one 21-day course before any patient is enrolled at the next dose level. Study drug administration will continue on an every 3-week schedule in the absence of progressive disease or unacceptable toxicity. A subsequent course of treatment may be administered at least 21 days after a prior LEM dose has been administered when study criteria are met.
Cohorts of 3 patients per dose level will be studied. This will be expanded to 6 if a DLT occurs, followed by a total of 6 patients at a possible MTD.
PROJECTED ACCRUAL: It is expected that 21 to 30 patients will be entered into the study to determine the MTD: 3 per dose level, expanded to 6 if DLT occurs, followed by a total of 6 patients at a possible MTD. The dose level identified as the MTD may then be expanded up to 12 patients to permit additional safety assessment.
|United States, California|
|City of Hope National Medical Center|
|Duarte, California, United States, 91010|
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|United States, Michigan|
|Barbara Ann Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|United States, Ohio|
|The Ohio State University|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Przemyslaw Twardowski, M.D.||City of Hope National Medical Center|