Liposome Encapsulated SN38 (LE-SN38) in Patients With Advanced Cancer
Liposome Encapsulated SN38 (LE-SN38) is an oncology drug product consisting of the active metabolite of irinotecan (CPT-11), a known anticancer drug, encapsulated in a liposome. Formulation of a relatively insoluble compound (SN38) and improvement in drug delivery (pharmacodynamic profile) may be obtained with liposomal formulations. An improved safety and efficacy profile, compared with the pro-drug CPT-11, may be possible. This rationale is supported by the results from animal toxicity studies in both the mouse and dog.
LE-SN38 will be infused intravenously every 3 weeks to assess safety and tolerability of study drug until there is disease progression or toxicity requiring early treatment discontinuation. Disease status will be assessed after every second cycle of treatment. In the event of disease progression, study treatment will be discontinued, all end-of-treatment study evaluations will be performed and further treatment options will be reviewed.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Study Start Date:||October 2002|
|Study Completion Date:||November 2010|
|Primary Completion Date:||August 2007 (Final data collection date for primary outcome measure)|
I. Determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of LE-SN38.
II. Determine the plasma pharmacokinetics of SN38 following IV administration of LE-SN38.
III. Observe any anti-tumor effects of LE-SN38.
This is an open-label study in patients with advanced solid tumors who have failed conventional therapy.
LE-SN38 will be administered IV over 90 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 21-day schedule in the absence of progressive disease or unacceptable toxicity. A subsequent course of treatment may be administered at least 21 days after receiving a prior dose of LE-SN38 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.
Disease status will be assessed after every second cycle. In the event of disease progression, study treatment will be discontinued and all end of treatment study evaluations will be performed.
PROJECTED ACCRUAL: Up to 40 patients will be enrolled.
|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:||Mayer Fishman, MD, PhD||H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida|
|Principal Investigator:||Patricia LoRusso, DO||Barbara Ann Karmanos Cancer Institute, Detroit, Michigan|
|Principal Investigator:||Eric Kraut, MD||The Ohio State University, Columbus, Ohio|