A Phase 2 Study of ASONEP™ to Treat Unresectable and Refractory Renal Cell Carcinoma
This Phase 2a study will investigate the efficacy, safety and tolerability of ASONEP™ (sonepcizumab/LT1009) when administered intravenously once a week, every 4 weeks (or cycle), to subjects with refractory renal cell carcinoma (RCC) until the disease progresses. Subjects who have failed 3 prior treatments for RCC including vascular endothelial growth factor (VEGF) and/or mammalian target of rapamycin (mTOR) inhibitors or who have tumors that cannot be surgically removed will be eligible for screening.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Multi-Center, Open-Label, Single-Arm, Phase 2 Study of ASONEP™ (Sonepcizumab/LT1009) Administered as a Single Agent to Subjects With Refractory Renal Cell Carcinoma|
- Progression-Free Survival [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]The study will use a two-cohort design based on an 8-week PFS rate. Treatment will be considered promising if at least 12 out of the first 22 eligible subjects entered in the Cohort 1 of the study are progression free at Week 8. Enrollment of Cohort 2 will then proceed and be considered worthy of further evaluation if at least 25 out of 39 eligible subjects are progression free at Week 8. If no efficacy signal is observed after enrollment of 22 subjects in Cohort 1, the second cohort will not be enrolled and the clinical study may be stopped.
- Safety and Tolerability - Incidence and frequency of adverse events and serious adverse events [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]The incidence and frequency of adverse events and serious adverse events
- Pharmacokinetics Trough Concentrations [ Time Frame: Pre-dose, weeks 1, 2, 4 of Cycle 1; pre-dose, weeks 2, 4 of Cycle 2 ] [ Designated as safety issue: No ]Descriptive statistics (mean, median, standard deviation and coefficient of variation) will be used to summarize trough concentrations. For subjects testing positive for anti-drug antibodies (ADA) to ASONEP, the relationship between plasma ADA titers and ASONEP trough concentrations will be evaluated.
- Tumor Response Rate [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]Imaging-based tumor assessments will be performed and response determined according to RECIST 1.1 criteria
- Changes in Surrogate Markers [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]Blood samples will be drawn for lymphocyte, antibody, cytokine, VEGF and basic fibroblast growth factor (bFGF) analysis
- Changes in Anti-drug Antibodies [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]Plasma samples will be evaluated for presence of ADA. If presence of ADA in plasma is confirmed, titers of anti-ASONEP will be determined.
|Study Start Date:||February 2013|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
ASONEP will be administered by intravenous infusion over 90 minutes at 15 mg/kg once a week every 4 consecutive weeks per cycle
LT1009-Onc-002 is a Phase 2a open-label, multi-center study designed to evaluate the efficacy and safety of ASONEP (sonepcizumab/LT1009) monotherapy in subjects with advanced, unresectable, refractory RCC who have previously failed up to 3 therapies, including VEGF and/or mTOR inhibitors. Two cohorts will be enrolled for a total of up to 39 subjects. Subjects will receive an intravenous (IV) infusion of ASONEP™ over 90 minutes at 24 mg/kg once a week and progression-free survival (PFS) will be assessed after 8 weeks of treatment. Cohort 1 will enroll approximately 22 subjects. A second cohort of up to 17 subjects will be enrolled if at least 12 out of 22 subjects from Cohort 1 demonstrated PFS at 8 weeks. Weekly dosing will take place from the date of randomization until the date of first documented progression or date of death from any cause, whichever comes first.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01762033
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010|
|United States, Florida|
|Florida Cancer Specialists|
|Fort Myers, Florida, United States, 33908|
|Florida Cancer Specialists|
|Inverness, Florida, United States, 34453|
|United States, South Carolina|
|Medical University of South Carolina|
|Charleston, South Carolina, United States, 29425|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37203|
|Study Director:||Susan Hazel||Lpath, Inc.|