Dose-Escalation Safety and Pharmacokinetic Study of Iso-Fludelone in Patients With Advanced Solid Tumors
Iso-fludelone is a type of chemotherapy drug called an epothilone. Epothilones are drugs that attach to proteins in your body called "tubulins". Tubulins help cells to grow, and are found in both normal and cancer cells. When research animals with cancer were given the study drug, Iso-fludelone, the drug attached itself to "tubulin" and slowed or stopped the cancer cells from growing. Other types of epothilones have been tested in cancer patients and were found to be safe. A similar epothilone drug and other drugs called taxanes are currently approved by the FDA for treating certain types of cancers.
The purpose of this study is to see the effects, good and/or bad, of this investigational drug, Iso-fludelone, on cancer. The term "investigational" means the study drug being tested has not been approved by the United States Food and Drug Administration (FDA) or other regulatory agencies. This study is the first time the investigators are using iso-fludelone in people. This is a Phase I study. In a Phase I study, the first people to receive the drug are given a fairly low dose.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I, Open-Label, Dose-Escalation Safety and Pharmacokinetic Study of Iso-Fludelone in Patients With Advanced Solid Tumors|
- To determine the maximum tolerated dose (MTD) [ Time Frame: 2 years ] [ Designated as safety issue: No ]The MTD is defined as the dose that results in DLT in 25% of all evaluable patients.
- To determine the dose limiting toxicity (DLT), safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Toxicities and adverse events will be assessed using the NCI CTC version 4.0
- To evaluate the plasma pharmacokinetics of iso-fludelone when administered intravenously [ Time Frame: over 6 hours (+/- 30 minutes) on a day 1 every 21 days schedule ] [ Designated as safety issue: No ]All PK analyses will be performed using the WinNonlin computer program; version 5.3 Pharsight Corporation, Mountain View, CA). PK Model selection will be based on a visual inspection of goodness of fit plots (observations vs. predictions, residuals and weighted residuals vs. predictions). The assay values (concentrations vs times) will be used to calculate individual-specific elimination rate constant (Ke), time to maximum Iso-fludelone concentration (Tmax), maximum Iso-fludelone concentration (Cmax) and area under the concentration-time curve (AUC) values.
- To describe and assess any preliminary evidence of anti-tumor activity of iso-fludelone [ Time Frame: every 6 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||June 2011|
|Estimated Study Completion Date:||June 2015|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Experimental: Patients with Advanced Solid Tumors
The trial was initially designed as a 3 hour IV infusion of iso-fludelone every 3 weeks with three dose-escalation stages (12 patients), however it has been amended to study iso-fludelone administered over 6 hours (+/- 30 minutes) every 3 weeks schedule.
Iso-fludelone will be administered IV over 6 hours (+/- 30 mins) on Day 1 of every 3 week cycle.
Other Name: KOS-1803
Please refer to this study by its ClinicalTrials.gov identifier: NCT01379287
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Mrinal Gounder, MD||Memorial Sloan Kettering Cancer Center.|