Dose Escalation Study of NKP-1339 to Treat Advanced Solid Tumors
The purpose of this study is to determine the safety and maximal tolerated dose of NKP-1339, a ruthenium containing compound administered intravenously on a weekly schedule, in patients with advanced solid tumors. The responses to treatment in this population will be evaluated. In addition, the PD and PK properties of the compound will be explored.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Dose Escalation Study of NKP-1339 Administered on Days 1, 8 and 15 of Each 28-Day Cycle in Patients With Advanced Solid Tumors Refractory to Treatment|
- Number of participants with related adverse events [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]The incidence and severity of related adverse events and laboratory abnormalities will be used to assess the safety and tolerability of NKP-1339.
- Composite of pharmacokinetics [ Time Frame: 0, 0.25, 0.5, 1, 2, 4, 6, 10 and 24 hours ] [ Designated as safety issue: No ]Plasma and urine samples will be analyzed to determine Cmax, Tmax, AUC, terminal elimination rate, elimination half-life, clearance,and volume of distribution.
- To report any responses to NKP-1339 in subjects with advanced tumors [ Time Frame: >8 weeks ] [ Designated as safety issue: No ]Tumor assessments every 2 cycles if patients continue treatment beyond 2 Cycles. Treatment is allowed beyond 2 cycles in patients who achieved at least stable disease, at the discretion of investigator and consent of the patient.
- To explore pharmacodynamic endpoints which may be of use in the further development of NKP-1339 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]Transferrin, transferrin receptor and GRP-78 in plasma.
|Study Start Date:||September 2009|
|Estimated Study Completion Date:||May 2013|
|Estimated Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
NKP-1339 will be administered in single patient cohorts until ≥ Grade 2 toxicity encountered, at which time cohorts converted to a standard 3 + 3 dose escalation scheme.
When MTD is reached, an expanded cohort of up to 25 patients will be enrolled at the MTD.
NKP-1339 is administered as a 30-90 minute IV infusion (based on volume to be infused) on days 1, 8, and 15 of a 28 day cycle.
NKP-1339 is a novel GRP78 targeted ruthenium based anti-cancer compound which is intravenously administered. GRP78 is a key regulator of misfolded protein processing, which is unregulated in cancer cells. In nonclinical anti-tumor studies, NKP-1339 showed activity against many tumor types, including those resistant to platinum and other standard anti-cancer agents. This Phase I trial evaluates the safety, tolerability, maximum tolerated dose, pharmacokinetics, and pharmacodynamics of NKP-1339.
|United States, Arizona|
|TGEN Clinical Research Services at Scottsdale Healthcare|
|Scottsdale, Arizona, United States, 85258|
|United States, Tennessee|
|The Sarah Cannon Research Institute|
|Nashville, Tennessee, United States, 37203|
|Principal Investigator:||Daniel D. Von Hoff, MD||TGEN Clinical Research Services at Scottsdale Healthcare|
|Principal Investigator:||Howard A. Burris, III, MD||The Sarah Cannon Research Institute|