A Dose Escalation Study of OMP-54F28 in Subjects With Solid Tumors
This is an open-label Phase 1 dose escalation study of OMP-54F28 in subjects with a solid tumor for which there is no remaining standard curative therapy. 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 OMP-54F28 until disease progression. All subjects will receive Vitamin D3 daily and calcium carbonate twice daily from Day 0 through 30 days following the discontinuation of OMP-54F28.
Dose escalation will be conducted to determine the maximum tolerated dose (MTD). Subjects will be dosed at 0.5, 1, 2.5, 5, and 10 mg/kg administered IV once every 3 weeks. No dose escalation or reduction will be allowed within a dose cohort. Intermediate doses (i.e., doses between the dose levels listed above) may also be tested upon agreement with the investigators and the study sponsor. In addition, alternate dosing schedule cohorts of OMP-54F28 (eg. every 4 week or every 6 week dosing) can be studied upon agreement with the investigators and the study sponsor. These alternative less frequent dosing schedules may be evaluated if emerging data suggest that once every 3 week dosing results in tolerability concerns. 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. 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 Days 0-28. Dose escalation for newly enrolled subjects, if appropriate, will occur after all subjects in a cohort have completed their Day 28 DLT assessment. Subjects who have a >2-fold increase of their fasting β-CTX or a decline of >3% in their bone mineral density (BMD) from screening or a T-score decline to <-2.5 in the total femur or L1-L4 DEXA scan measurement will be started on zoledronic acid. Subjects with stable disease or a response at Day 56 will be allowed to continue to receive OMP-54F28 until disease progression. An additional 6 subjects will be enrolled in an expansion cohort at the highest dose level that results in <2 of the 6 subjects experiencing a Grade 3 (not including a Grade 3 infusion reaction that resolves in 24 hours) or Grade 4 adverse event (DLT). Tumors of particular interest for inclusion in the expansion cohort include sarcomas, basal cell carcinoma, ovarian cancer, desmoid tumors and prostate cancer given the known importance of the Wnt pathway in these malignancies.
|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-54F28 in Subjects With Solid Tumors|
- • To determine the safety of OMP-54F28 in subjects with previously treated solid tumors [ Time Frame: Subjects will be assessed for dose limiting toxicities from Days 0-28. Adverse events will be reported through 30 days after the last dose. ] [ Designated as safety issue: Yes ]
- To determine the pharmacokinetics of OMP-54F28 in subjects with previously treated solid tumors [ Time Frame: Baseline,end of infusion,0.5,1,3,6,24, and 72 hours post-infusion (1st infusion) 0.5, 1, 3, 6, 24, 72, and 168 hours (3rd infusion),before/end 2nd infusion,Days 7, 14, 28, and 35. After termination: Weekly for the first 4 weeks, then at Week 8 and 12 ] [ Designated as safety issue: No ]The pharmacokinetic (PK) parameters to be assessed are study drug half-life (t½), volume of distribution (Vd), and clearance (CL).
- To determine the immunogenicity of OMP-54F28 in subjects with previously treated solid tumors [ Time Frame: Subjects will be assessed during screening ,every 4 weeks while on study drug, at the time of treatment termination, then weekly for the first 4 weeks, then at Week 8 and 12 following discontinuation of study drug ] [ Designated as safety issue: No ]
- To assess the preliminary efficacy of OMP-54F28 in subjects with previously treated solid tumors [ Time Frame: Every 56 days until disease progression ] [ Designated as safety issue: No ]The response outcome in patients will be determined.
|Study Start Date:||June 2012|
|Estimated Study Completion Date:||July 2015|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01608867
|United States, Arizona|
|Pinnacle Oncology Hematology,|
|Scottsdale, Arizona, United States, 85258|
|United States, Colorado|
|University of Colorado Hospital|
|Aurora, Colorado, United States, 80045|
|United States, Michigan|
|University of Michigan Health System|
|Ann Arbor, Michigan, United States, 48109|