A Dose Escalation Study of OMP-54F28 in Subjects With Solid Tumors
Condition: Solid Tumors
MeSH terms: Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    


Intervention name(s): OMP-54F28
Intervention type(s): Biological
Intervention description(s): dose escalation of 0.5, 1, 2.5, 5, and 10 mg/kg administered IV once every 3 weeks
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Phase 1; dose escalation; histologically confirmed; malignancy; metastatic