A Dose Escalation Study of OMP-59R5 in Subjects With Solid Tumors
This is an open-label Phase 1 dose escalation study of OMP-59R5 in subjects with previously treated solid tumors for which there is no remaining standard curative therapy and no therapy with a demonstrated survival benefit. Up to 44 subjects will be enrolled at up to 2 centers. Subjects will be assessed for safety, immunogenicity, pharmacokinetics, biomarkers, and efficacy. No formal interim analyses will be performed.
Prior to enrollment, subjects will undergo screening to determine study eligibility. Upon enrollment, subjects will receive intravenous (IV) infusions of OMP-59R5 at a assigned dosing schedule for 56 days. After 56 days, subjects will be assessed for disease status. If there is no evidence of disease progression or if the tumor is smaller, then subjects may continue to receive IV infusions of OMP-59R5 every week until disease progression.
Dose escalation will be conducted to determine the maximum tolerated dose (MTD). No dose escalation or reduction will be allowed within a dose cohort. The first 2 subjects enrolled in a cohort will not be treated on the same day. The dose may be administered at any time during the day. Three subjects will be treated at each dose level if no dose-limiting toxicities (DLTs) are observed. The first 2 subjects in each cohort will not be started on OMP-59R5 on the same day. If 1 of 3 subjects experiences a DLT, that dose level will be expanded to 6 subjects. If 2 or more subjects experience a DLT, no further subjects will be dosed at that level and 3 additional subjects will be added to the preceding dose cohort unless 6 subjects have already been treated at that dose level. Subjects will be assessed for DLTs from the time of the first dose through 28 days. Dose escalation for newly enrolled subjects, if appropriate, will occur after all subjects in a cohort have completed their Day 28 DLT assessment. Subjects with stable disease or a response at Day 56 will be allowed to continue to receive weekly doses of OMP-59R5 until disease progression. An additional 14 subjects will be enrolled at the highest dose level that result in <2 of the 6 subjects experiencing a DLT.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 Dose Escalation Study of OMP-59R5 in Subjects With Solid Tumors|
- To determine the safety of OMP-59R5 in subjects with previously treated solid tumors [ Time Frame: continuous ] [ Designated as safety issue: Yes ]The number of patients experiencing Adverse Events will be reported.
- To determine the pharmacokinetics of OMP-59R5 in subjects with previously treated solid tumors [ Time Frame: First 8 doses and following treatment termination ] [ Designated as safety issue: No ]The half-life, volume of distribution, and clearance will be determined
- To determine the immunogenicity of OMP-59R5 in subjects with previously treated solid tumors [ Time Frame: continuous ] [ Designated as safety issue: No ]The rate of neutralizing antibodies will be determined
- To assess the preliminary efficacy of OMP-59R5 in subjects with previously treated solid tumors [ Time Frame: continuous ] [ Designated as safety issue: No ]The response outcome in patient will be determined
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||August 2015|
|Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01277146
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|United States, Texas|
|South Texas Accelerated Research Therapeutics|
|San Antonio, Texas, United States, 78229|
|Principal Investigator:||David C. Smith, MD||University of Michigan|
|Principal Investigator:||Anthony W. Tolcher, MD||South Texas Accelerated Research Therapeutics, LLC|