Study of NK012 and 5-FU/LV in Solid Tumors Followed by Dose Expansion in Colorectal Cancer
The primary objective is to determine the maximum tolerated dose/recommended phase II dose of the combination regimen of NK012 and 5-fluorouracil in patients with advanced solid tumors.
Advanced Solid Tumors
Metastatic Colorectal Cancer
Drug: NK012 and 5-FU
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of NK012 in Combination With Infusional 5-fluorouracil and Leucovorin in Patients With Advanced Solid Tumors Followed by a Dose Expansion Phase in Patients With Metastatic Colorectal Cancer|
- Number of patients with dose-limiting toxicity as determinant of the maximum tolerated dose/recommended dose [ Time Frame: From date of first dose to off-study (or 30 days since last dose) ] [ Designated as safety issue: Yes ]
- Number of patients with adverse events as a measure of safety and tolerability [ Time Frame: From date of first dose to off-study (or 30 days since last dose) ] [ Designated as safety issue: Yes ]
- Tumor measurements, as a measure of efficacy [ Time Frame: Baseline, then every on average every 2 months until off-study ] [ Designated as safety issue: No ]Efficacy, based on RECIST 1.1, will be assessed in all solid tumors, and in a specific subset of patients with colorectal cancer
- Area under the plasma concentration versus time curve (AUC) of NK012 and fluorouracil [ Time Frame: 15,30min, 1,6,24,46.5,48,72hrs, Wk1,2,3,4 of cycle 1 ] [ Designated as safety issue: No ]
- Peak Plasma Concentration (Cmax) of NK012 and fluorouracil [ Time Frame: 15,30min, 1,6,24,46.5,72hrs, week 1,2,3,4 of cycle 1 ] [ Designated as safety issue: No ]
|Study Start Date:||August 2010|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Drug: NK012 and 5-FU
NK012 infusion on Day 1 of each 28 day cycle 5-FU continuous infusion on Days 1 and 15 of each 28 day cycle
On Day 1 of each 28 day cycle, NK012 will be administered as a 30 minute IV infusion, followed by continuous infusion of 5-FU over 46 hours. On Day 15 of each cycle, patients again receive 5-FU continuous infusion. Treatment is expected to continue for 6 cycles, unless disease progression or the development of unacceptable toxicity requires discontinuation of the drug. At the discretion of the investigator, patients who show signs of benefit may continue beyond 6 cycles.
Once a MTD/RD has been determined for the combination regimen, a dose expansion cohort of patients with metastatic colorectal cancer will be treated at the determined MTD.
(Prior to Amendment 2, patients were receiving NK012 and 5-FU and leucovorin (LV). The dosing regimen was changed as of Amendment 2 to NK012 and 5-FU.)